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Good morning, class.

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Nice to see you again.

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Hope you had a great weekend.

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If you didn't, it wasn't
because of the weather.

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So here I am, once again a
member of the walking wounded,

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and we're talking about
carbohydrates today,

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as you may recall,
or at least we

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were at the end of our
discussion last time.

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And, we made the point that
these multiple hydroxyl groups

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on the carbohydrates,
on the one hand,

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determine the identity of
various kinds of sugars.

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Just the orientation, the
three-dimensional orientation

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of them, for one
thing, and for another

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that these multiple
hydroxyl groups represent

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the opportunity for
forming covalent bonds

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with other monosaccharides
as is indicated here

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in these disaccharides, or
covalent bonds end-to-end

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to create large molecules,
which will increasingly

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be the theme of our
discussion today, i.e.

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when I talk about
large molecules,

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we just used the phrase
generically, macromolecules,

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since in principle these end to
end joinings of molecules which

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involve the dehydration
and the formation

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of these covalent
bonds like right here

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can create molecules that
are hundreds, indeed even

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thousands of subunits long.

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So, here, if we're
talking about a polymer,

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we refer to each one
of these subunits

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of the polymer as
being a monomer,

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and the aggregate as a
whole as being a polymer.

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Here, we touched upon the fact
toward the end of last lecture,

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in fact, at the very end,
that one can cross-link

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these long, linear
chains of carbohydrates.

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And here, we see the
fact that glycogen,

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which is a form of glucose
that is stored in our liver

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largely, and to a small
extent in the muscles

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actually is cross-branched.

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So, if one draws on a much
smaller scale a glycogen

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molecule, one might draw a
picture that looks like this.

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And it looks almost
like a Christmas tree

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with multiple branches.

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And, the purpose
of this is actually

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to sequester the glucose,
to store the glucose

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into metabolically inactive
form until the time comes

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that the organism
needs, once again,

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the energy that is
stored in the glucose

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upon which occasion these
bonds are rapidly broken down

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and the glucose is
mobilized and put

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into the circulation
for eventual disposition

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and use in certain,
specific tissues.

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While it's encumbered in these
high molecular weight polymers,

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the glucose is essentially
metabolically inactive.

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The body doesn't
realize it's there.

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And, we can, as a consequence
store large amounts of energy

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in these glycogen molecules.

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And it can be stored
there indefinitely.

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Now, the fact is this idea
of end-to-end polymerization

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that I just mentioned
can be extended

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to other macromolecules which
also become linked end-to-end

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in specific kinds of polymers.

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And here, we are moving,
now, into the notion

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of talking about amino acids.

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And, we're talking
about proteins.

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If we look at an amino
acid, what we see

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is it has an important
structure like this.

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Here's a central carbon ?

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for, in principle,
the distinct side

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chains where R represents
some side chain that

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can be any one of,
as we'll see shortly,

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20 distinct identities.

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But, all the amino acids
share in common the property

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that they have this
overall structure.

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And, as you may recall from
our discussions of last week,

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at neutral pH, an amino
acid of this sort, whatever

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R is, wouldn't look
like this at all

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because the amine group would
attract an extra proton,

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causing it to become
positively charged.

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And, the carboxyl group
would release a proton,

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causing it to become
negatively charged.

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And, as you might
deduce from this,

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at very low pHn due to the
greatly increased concentration

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of protons, free
protons in the solution,

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the equilibrium would
be driven more in favor

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of reattaching a proton
to the carboxyl group

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just because there are so
many of these protons around.

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Conversely, at very high pH,
where the hydroxyl ions are

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in predominance, they obviously
tend to scavenge protons,

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reducing the level of protons
to very low levels in the water.

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And, under very
high pH conditions,

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this proton would be
released and pulled away

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by the hydroxyl ions causing
this amine group once again

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to return to its
negative charge state.

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Now, the fact of the matter
is that these amino acids

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exist in a very specific
three-dimensional

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configuration.

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And that's illustrated
much more nicely here

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than I could possibly draw on
the board, which in any case

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would be hopeless.

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And, you can see the
principle that once

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you have four distinct side
groups coming off of carbon,

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that there is, in principle, two
different ways to create them.

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And, this is sometimes
called chirality.

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Chiral, you see, is
the form right here.

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The hands are chiral.

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If I try, as much as
I will, to superimpose

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one hand on top of another.

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It doesn't work because they are
mirror images of one another,

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which are asymmetrical.

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And, as a consequence, we see
a similar kind of relationship

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occurring here where we see that
these two forms of amino acids

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could, in principle, exist.

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And, they are not
interchangeable

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unless one breaks one of
the bonds and reforms it.

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These two forms are
called the L and the D,

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and it turns out that the
L form is the one that's

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used by virtually all life
forms on the planet, i.e.

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there was an
arbitrary choice made

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sometime about 3 billion
years ago or more to use

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one of the three
dimensional configurations,

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and not to use the other.

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The other is found in
certain rare exceptions,

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but virtually all life forms
on this planet use the L form.

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That said, by the way, this
indicates some of the arbitrary

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decisions that were made early
during evolution because we

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could imagine on another planet
if life were to exist there

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and it were to depend
on amino acids,

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and that evolutionary system
might have chosen the D form.

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So, this is sort of
a luck of the draw.

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This is actually the
way things evolved here.

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And, what we begin to see, now,
is if we talk about proteins

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or if we wanted to be more
specific and use the more

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biochemical term ?polypeptide,?

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we see once again we have an
end-to-end joining system which

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is a bit different
from that which

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the monosaccharides employ to
create long chains of glycogen

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or of starch because here we
see once again a dehydration

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reaction where an amine
group and a carboxyl group

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are caused to shed their
hydroxyl and the proton,

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causing the formation
of a peptide bond.

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And here, we see this
important, very important

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biochemical entity, a
peptide bond consisting here

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of this carbonyl and
this nitrogen fused

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in this specific way.

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And, of course, if you recognize
this as being a peptide bond,

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then you can understand why
proteins are sometimes given

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the term ?polypeptide.?

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In some cases, if one has very
short stretches of amino acids

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linked end to end like this,
we talk about these being

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oligopeptides, where ?oligo?

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is the general term
used in biology

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to refer to a small
number of things

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rather than a large
number of things.

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And, once again, we have,
here, the possibility

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of extending this infinitely.

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There are no constraints,
in principle,

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on making this 500, 1,000,
even 2,000 amino acids long,

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where each one of these,
once again, is an amino acid,

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and where once again I'm being
very coy about the identities

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of R1 and R2, which, as I
will indicate very shortly,

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can be one of 20
distinct alternatives.

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Here, you see that
we are continuing

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this process of
peptide bond formation.

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And most importantly
here is the realization

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that there is a polarity
of elongation here.

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It doesn't move with equal
probability left or right,

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or right to left.

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We start at the amino end here.

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This is the amino end, and
this is the carboxyl end.

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The amino end and
the carboxyl end,

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and invariably, again
because of the way life

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has evolved on this
planet, the new amino acid

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is added on the carboxyl end.

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And so, when one often
talks about proteins,

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one refers to their N terminal,
and to their C terminal

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ends, these referring
obviously to the amino group

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at one end and a carboxyl
and at the other end

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so that polarity is always a
directed synthesis adding it

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on C-terminal end,
in other words

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to use a short-hand notation,
we think about proteins

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as going with this
polarity N toward C.

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Things are growing at the C
terminal end progressively.

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And, each time one can imagine
the addition of an amino acid

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on the end of it.

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So, again, it can be extended,
in principle, indefinitely.

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Keep in mind as well, something
that's implicit in everything

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I'm telling you but I won't
always mention it explicitly,

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and that is virtually
every biochemical reaction

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is reversible.

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And therefore, if one is
able to form a peptide bond,

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one is able to break it down by
biological means as well, i.e.

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by introducing a water molecule
back in and thereby using

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the process of hydrolysis,
which is the breakdown

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of a bond through the
introduction of a water

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molecule to destroy the
previously created bond.

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To use an MIT phrase, the
reversibility is intuitively

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obvious because if you
are able to make a, well,

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I don't know if it?s still used,
but it was used in the late

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Stone Age around here.

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Anyhow, any biochemical
action must be reversible

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because if, for example,
this polymerization were

201
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irreversible, then all
the protein that was ever

202
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synthesized on the surface of
the planet over the last 3 1/2

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billion years would
accumulate progressively.

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And obviously, that
doesn't happen.

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And therefore,
macromolecular synthesis,

206
00:11:04,550 --> 00:11:06,190
to the extent that
it proceeds forward,

207
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obviously must go the
other direction as well.

208
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And the resulting concentration
of a complete protein

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is known as its steady state.

210
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So we might make a
protein at one rate

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and break it down
at the same rate.

212
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And its steady-state
concentration

213
00:11:23,160 --> 00:11:26,030
represents the compromise
between these two, i.e.,

214
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the concentration
of such a protein

215
00:11:28,380 --> 00:11:31,459
that we might observe at
any one point in time.

216
00:11:31,459 --> 00:11:32,750
Indeed, the term ?steady-state?

217
00:11:32,750 --> 00:11:37,000
could be expanded to any process
in which there is a synthesis

218
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and there is a
breakdown of something.

219
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And the equilibrium
concentration

220
00:11:41,160 --> 00:11:45,190
which results is, once again,
called the steady-state

221
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of that molecule.

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Now, let's get down
to the nitty-gritty,

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which is obviously
something which

224
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we can't avoid for very long,
which is to say the R's, i.e.

225
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the side chains.

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Once again, here we see
an arbitrary artifact

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of very early evolution
in the biosphere

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because there are, in effect, 20
different side chains creating

229
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20 distinct amino
acids, which are

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used in proteins by all
organisms on this planet.

231
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Again, there are
rare exceptions,

232
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certain fungi and
certain bacteria

233
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are able to make
unusual amino acids.

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But these are the
basic building blocks

235
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of virtually all life
forms on the planet.

236
00:12:28,440 --> 00:12:30,440
99.99% of all the
protein that is created

237
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is synthesized through the
polymerization of these 20

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amino acids.

239
00:12:36,800 --> 00:12:40,540
And, by the way, one of
the amino acids, glycine,

240
00:12:40,540 --> 00:12:42,940
over here, you
see it right here,

241
00:12:42,940 --> 00:12:46,010
violates this rule of chirality.

242
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And, you will
recall before I said

243
00:12:47,990 --> 00:12:52,920
that because there are
four distinct amino acids,

244
00:12:52,920 --> 00:12:55,730
four distinct side chains
around a central carbon

245
00:12:55,730 --> 00:12:57,340
sometimes called
the alpha carbon,

246
00:12:57,340 --> 00:13:00,280
you always have a
handedness of amino acids.

247
00:13:00,280 --> 00:13:04,560
But this notion cannot
be respected in the case

248
00:13:04,560 --> 00:13:09,282
of glycine seen up here simply
because we don't have four

249
00:13:09,282 --> 00:13:11,740
distinct, here's the central
carbon where I'm pointing with

250
00:13:11,740 --> 00:13:15,881
the red, and here these two
hydrogens are equivalent to one

251
00:13:15,881 --> 00:13:16,380
another.

252
00:13:16,380 --> 00:13:17,680
They are not four
distinct chains.

253
00:13:17,680 --> 00:13:19,440
There's only three
distinct chains here.

254
00:13:19,440 --> 00:13:22,130
So glycine violates
this rule of chirality,

255
00:13:22,130 --> 00:13:24,530
of left- and right-handedness.

256
00:13:24,530 --> 00:13:27,010
And here, by the
way, the side chain,

257
00:13:27,010 --> 00:13:30,620
which in all of these cases
is depicted as extending off

258
00:13:30,620 --> 00:13:33,140
to the right of each
amino acid, the side chain

259
00:13:33,140 --> 00:13:38,040
is simply an H, simply a
proton, a hydrogen atom.

260
00:13:38,040 --> 00:13:41,870
In fact, what we see
about these amino acids

261
00:13:41,870 --> 00:13:44,280
is that the side
chains have quite

262
00:13:44,280 --> 00:13:46,900
distinct biochemical properties.

263
00:13:46,900 --> 00:13:50,040
And that begins to
impress us with the notion

264
00:13:50,040 --> 00:13:53,250
that proteins and their
biochemical attributes

265
00:13:53,250 --> 00:13:57,100
can be dictated by the
identities of the amino acids

266
00:13:57,100 --> 00:13:59,220
that are used to construct them.

267
00:13:59,220 --> 00:14:01,830
We can talk about the
notion of nonpolar

268
00:14:01,830 --> 00:14:05,960
versus polar amino
acids, i.e., amino acids

269
00:14:05,960 --> 00:14:10,010
which have poor
affinity for water.

270
00:14:10,010 --> 00:14:14,990
They don't have a separation
of plus and minus charges.

271
00:14:14,990 --> 00:14:19,600
And as a consequence, they are
a little bit or quite a bit

272
00:14:19,600 --> 00:14:21,402
hydrophobic.

273
00:14:21,402 --> 00:14:23,610
Now, you will say, well,
how can they be hydrophobic,

274
00:14:23,610 --> 00:14:25,680
because here this
oxygen is charged,

275
00:14:25,680 --> 00:14:28,100
and here this amine
group is charged?

276
00:14:28,100 --> 00:14:30,560
That would make it
highly hydrophilic.

277
00:14:30,560 --> 00:14:32,390
But keep in mind,
when I'm talking

278
00:14:32,390 --> 00:14:35,180
about these amino acids,
I'm not talking about them

279
00:14:35,180 --> 00:14:37,460
when they are in a
single amino acid form.

280
00:14:37,460 --> 00:14:39,440
I'm talking about
their properties

281
00:14:39,440 --> 00:14:43,650
once they have been polymerized
into state like this.

282
00:14:43,650 --> 00:14:46,500
And, once they are polymerized
into state like this,

283
00:14:46,500 --> 00:14:51,580
the NH2 and CO charging,
that is, the charge here

284
00:14:51,580 --> 00:14:53,360
and the charge here
become irrelevant

285
00:14:53,360 --> 00:14:55,710
because this oxygen
and this amine group

286
00:14:55,710 --> 00:14:58,120
are both tied up
in covalent bonds.

287
00:14:58,120 --> 00:15:01,640
And, this acquisition of
a proton and this shedding

288
00:15:01,640 --> 00:15:04,670
of a proton over
here cannot occur,

289
00:15:04,670 --> 00:15:07,330
because both of
these atoms, O and N,

290
00:15:07,330 --> 00:15:09,640
are involved in covalent bonds.

291
00:15:09,640 --> 00:15:14,730
So therefore, when we talk about
nonpolar and polar amino acids,

292
00:15:14,730 --> 00:15:18,330
keep in mind we are focusing
on the biochemical properties

293
00:15:18,330 --> 00:15:21,990
of the side chain because
the central backbone

294
00:15:21,990 --> 00:15:24,930
of the polypeptide and
the central backbone

295
00:15:24,930 --> 00:15:26,581
is defined quite clearly here.

296
00:15:26,581 --> 00:15:28,080
Here's the central
backbone, and you

297
00:15:28,080 --> 00:15:33,380
see it has a quite repeating
structure, N, C, C, N, C, C, N,

298
00:15:33,380 --> 00:15:34,850
C, C, this is invariant.

299
00:15:37,360 --> 00:15:41,790
What changes, and what defines
the biochemical attributes

300
00:15:41,790 --> 00:15:45,410
of this oligopeptide,
or a polypeptide,

301
00:15:45,410 --> 00:15:47,560
are the identities of
these side chains, which

302
00:15:47,560 --> 00:15:50,070
again are plotted on
this particular graph.

303
00:15:50,070 --> 00:15:53,710
You have a different version
in your book off to the right.

304
00:15:53,710 --> 00:15:56,880
Here, you see, we have a proton,
a methyl group, a valine,

305
00:15:56,880 --> 00:16:01,360
a lucine, an isolucine,
and the differences

306
00:16:01,360 --> 00:16:08,270
between this suggests these
are all quite aliphatic, quite

307
00:16:08,270 --> 00:16:14,160
similar to the propane that
we talked about last time,

308
00:16:14,160 --> 00:16:15,210
or the hexane.

309
00:16:15,210 --> 00:16:18,440
That is to say, these are
quite hydrophobic side groups.

310
00:16:18,440 --> 00:16:22,730
And, as such, if there were a
polypeptide, we can imagine,

311
00:16:22,730 --> 00:16:24,870
and you put the
polypeptide in water,

312
00:16:24,870 --> 00:16:28,080
you can imagine that these
amino acids would not

313
00:16:28,080 --> 00:16:31,110
like to be directly confronting
the water because of the fact

314
00:16:31,110 --> 00:16:33,140
that they are hydrophobic.

315
00:16:33,140 --> 00:16:37,150
Methionine is also
a bit hydrophobic.

316
00:16:37,150 --> 00:16:41,130
I'm equivocating
there because the S

317
00:16:41,130 --> 00:16:44,590
has a slight degree
of hydrophilicity.

318
00:16:44,590 --> 00:16:46,690
It has a slight
degree of polarity,

319
00:16:46,690 --> 00:16:48,230
but not really that much.

320
00:16:48,230 --> 00:16:50,600
And, these aromatic
side chains here,

321
00:16:50,600 --> 00:16:52,810
because they have
these benzene rings,

322
00:16:52,810 --> 00:16:55,340
consequently are
called aromatic.

323
00:16:55,340 --> 00:16:58,520
These are quite
strongly hydrophobic.

324
00:16:58,520 --> 00:17:02,240
So, they really hate to
be in the intimate contact

325
00:17:02,240 --> 00:17:03,690
with water.

326
00:17:03,690 --> 00:17:06,530
Here, on the other hand, let's
look at these side chains

327
00:17:06,530 --> 00:17:13,530
because here we have
strongly polar molecules,

328
00:17:13,530 --> 00:17:14,970
side chains again.

329
00:17:14,970 --> 00:17:17,380
Keep in mind we are
focusing on the side chains.

330
00:17:17,380 --> 00:17:19,470
Here we see serine with
the hydroxyl group that

331
00:17:19,470 --> 00:17:22,280
can form hydrogen bonds with
the water, threonine, which

332
00:17:22,280 --> 00:17:25,460
has its own hydroxyl
group, asparagine,

333
00:17:25,460 --> 00:17:28,800
which has two atoms here,
this carbonyl and the NH2,

334
00:17:28,800 --> 00:17:33,220
both of which can form
hydrogen bonds with the water,

335
00:17:33,220 --> 00:17:35,520
as can glutamine.

336
00:17:35,520 --> 00:17:37,540
So, these are quite hydrophilic.

337
00:17:37,540 --> 00:17:41,340
They are not as fanatically
hydrophilic as these charge

338
00:17:41,340 --> 00:17:43,570
molecules where the
side chains are not

339
00:17:43,570 --> 00:17:46,210
just capable of
forming hydrogen bonds.

340
00:17:46,210 --> 00:17:48,580
In this lower group
here, the side chains

341
00:17:48,580 --> 00:17:50,750
are capable of
undergoing ionization.

342
00:17:50,750 --> 00:17:53,150
So they're actually
strongly charged.

343
00:17:53,150 --> 00:17:56,820
And here, we see here
the carboxyl group,

344
00:17:56,820 --> 00:17:59,390
and our aspartic acid
and glutamic acid

345
00:17:59,390 --> 00:18:01,410
has actually
discharged its proton,

346
00:18:01,410 --> 00:18:03,630
becoming negatively charged.

347
00:18:03,630 --> 00:18:05,950
These are acidic
amino acids, by virtue

348
00:18:05,950 --> 00:18:09,130
of the carboxyl group they
have, basic amino acids

349
00:18:09,130 --> 00:18:12,600
here: arginine,
lysine, and histidine,

350
00:18:12,600 --> 00:18:15,380
all acquire a
positively charged side

351
00:18:15,380 --> 00:18:18,110
chain by virtue
of these nitrogen

352
00:18:18,110 --> 00:18:21,100
here which have a strong
affinity for pulling away

353
00:18:21,100 --> 00:18:25,760
protons or abstracting protons
from the aqueous solvent.

354
00:18:25,760 --> 00:18:30,080
And so, we have a whole
gradient of hydrophilicity

355
00:18:30,080 --> 00:18:32,510
down to hydrophobicity.

356
00:18:32,510 --> 00:18:35,260
And here, we have
intermediate structures.

357
00:18:35,260 --> 00:18:38,990
We also have some very
special idiosyncratic kinds

358
00:18:38,990 --> 00:18:40,310
of amino acids.

359
00:18:40,310 --> 00:18:43,610
Here is tyrosine, and tyrosine
is little bit schizophrenic

360
00:18:43,610 --> 00:18:44,230
again.

361
00:18:44,230 --> 00:18:47,340
It has this highly hydrophobic
aromatic group here,

362
00:18:47,340 --> 00:18:50,090
the benzene ring, which
hates to be in water,

363
00:18:50,090 --> 00:18:53,130
and the hydroxyl group which
actually is a friend of water.

364
00:18:53,130 --> 00:18:54,680
So, here, we have
something where

365
00:18:54,680 --> 00:18:57,710
its role is quite equivocal.

366
00:18:57,710 --> 00:19:01,090
Here, we have cystine,
as indicated here,

367
00:19:01,090 --> 00:19:03,190
and what's interesting
about the cystine group

368
00:19:03,190 --> 00:19:06,860
in this case is the SH
group, the side chain, the SH

369
00:19:06,860 --> 00:19:12,280
group, because this SH group
is able to form bonds with yet

370
00:19:12,280 --> 00:19:15,130
other SH groups
from other cystines.

371
00:19:15,130 --> 00:19:18,250
So, let's just look at the
cystine here for a moment.

372
00:19:18,250 --> 00:19:21,230
You see there's a CH2,
and then there's an SH.

373
00:19:21,230 --> 00:19:23,860
So, let's imagine, I'm not going
to draw all the atoms here,

374
00:19:23,860 --> 00:19:25,870
but let's imagine here
we have the CH2 group.

375
00:19:25,870 --> 00:19:29,270
I'm not drawing the
backbone, SH, over here.

376
00:19:29,270 --> 00:19:31,280
And, we can imagine
another protein chain,

377
00:19:31,280 --> 00:19:33,820
another polypeptide
chain down here.

378
00:19:33,820 --> 00:19:37,390
Again, I'm not
drawing the backbone,

379
00:19:37,390 --> 00:19:40,550
but I'm drawing
another SH like this.

380
00:19:40,550 --> 00:19:43,290
And, the fact is, under
the conditions of oxidation

381
00:19:43,290 --> 00:19:46,990
and reduction that operate
at least in the extracellular

382
00:19:46,990 --> 00:19:50,870
space, one can oxidize
this, these two,

383
00:19:50,870 --> 00:19:52,730
resulting in the
formation of what

384
00:19:52,730 --> 00:19:55,350
is known as a disulfide bond.

385
00:19:59,820 --> 00:20:02,280
So, here, we have now
for the first notion

386
00:20:02,280 --> 00:20:07,060
the idea that the polypeptide
chains can be covalently linked

387
00:20:07,060 --> 00:20:11,790
to one another through these
cross-links, as indicated here.

388
00:20:11,790 --> 00:20:14,130
Conversely, if you
add a reducing agent

389
00:20:14,130 --> 00:20:16,600
that will add
protons back to this,

390
00:20:16,600 --> 00:20:20,050
and reduce the oxidation
state of the sulfurs,

391
00:20:20,050 --> 00:20:25,400
once again causing the
disulfide bond to fall apart.

392
00:20:25,400 --> 00:20:27,880
Now, in principle,
these disulfide bonds

393
00:20:27,880 --> 00:20:31,070
could be used to link
two proteins together.

394
00:20:31,070 --> 00:20:33,230
But, more often than
not, if you look

395
00:20:33,230 --> 00:20:36,760
at the structure of
a single protein,

396
00:20:36,760 --> 00:20:38,900
here's the structure
of a single protein.

397
00:20:38,900 --> 00:20:44,750
And often, there are
intramolecular bonds,

398
00:20:44,750 --> 00:20:49,020
disulfide bonds, i.e.,
bonds from one domain

399
00:20:49,020 --> 00:20:51,410
of the protein to another,
from one part of the protein

400
00:20:51,410 --> 00:20:52,170
to the other.

401
00:20:52,170 --> 00:20:53,710
I'll draw them in right here.

402
00:20:53,710 --> 00:20:55,610
Here might be a disulfide bond.

403
00:20:55,610 --> 00:20:58,130
Here might be a disulfide
bond, and I could go on and on.

404
00:20:58,130 --> 00:21:00,100
There might be
another one over here.

405
00:21:00,100 --> 00:21:02,860
Why do we have these
disulfide bonds?

406
00:21:02,860 --> 00:21:05,410
Because as we will
indicate very shortly,

407
00:21:05,410 --> 00:21:07,710
the three-dimensional
structure of a protein

408
00:21:07,710 --> 00:21:11,070
is very specifically determined.

409
00:21:11,070 --> 00:21:12,680
A protein can only
function when it

410
00:21:12,680 --> 00:21:14,640
assumes a certain
three-dimensional

411
00:21:14,640 --> 00:21:18,990
configuration, when it assumes
a certain three-dimensional,

412
00:21:18,990 --> 00:21:25,090
stereochemical configuration.

413
00:21:25,090 --> 00:21:27,250
When we talk about
stereochemistry,

414
00:21:27,250 --> 00:21:29,790
we are talking about the
three-dimensional structures

415
00:21:29,790 --> 00:21:32,040
of molecules, small and large.

416
00:21:32,040 --> 00:21:34,970
And, here, we begin to
touch on a theme of how

417
00:21:34,970 --> 00:21:39,470
these complex polypeptide chains
are able to create proteins

418
00:21:39,470 --> 00:21:42,340
that have very specific,
often very rigid,

419
00:21:42,340 --> 00:21:44,950
structures in
three-dimensional space.

420
00:21:44,950 --> 00:21:47,530
Part of this structural
rigidity is maintained

421
00:21:47,530 --> 00:21:52,760
by these covalent
disulfide bonds, which

422
00:21:52,760 --> 00:21:55,930
tightly link neighboring
regions, or even not

423
00:21:55,930 --> 00:22:00,640
so neighboring regions, of
a single polypeptide chain,

424
00:22:00,640 --> 00:22:03,290
these intramolecular links.

425
00:22:03,290 --> 00:22:06,310
This doesn't preclude there
being intermolecular links

426
00:22:06,310 --> 00:22:08,360
between two
polypeptide chains that

427
00:22:08,360 --> 00:22:12,760
are mediated as well
by the disulfide bonds.

428
00:22:12,760 --> 00:22:15,190
Here's another very
peculiar amino acid

429
00:22:15,190 --> 00:22:19,550
because what you see here
is at the side chain, which

430
00:22:19,550 --> 00:22:24,110
is CH2, CH2, CH2, CH2
is hydrogen bonded here

431
00:22:24,110 --> 00:22:26,260
to the amine group.

432
00:22:26,260 --> 00:22:29,790
It's not swinging
out in free space.

433
00:22:29,790 --> 00:22:31,280
I misspoke.

434
00:22:31,280 --> 00:22:35,020
What we see here is CH2,
CH2 is covalent bonded

435
00:22:35,020 --> 00:22:36,170
to the amine group.

436
00:22:36,170 --> 00:22:38,150
You pick that up, right?

437
00:22:38,150 --> 00:22:40,760
I was just testing you.

438
00:22:40,760 --> 00:22:41,410
Sure I was.

439
00:22:41,410 --> 00:22:44,040
OK, so here we see
a five-membered ring

440
00:22:44,040 --> 00:22:45,520
that's created.

441
00:22:45,520 --> 00:22:48,260
So here, this thing is not
swinging out in free space.

442
00:22:48,260 --> 00:22:51,900
It creates a five-membered ring
where the end of the side chain

443
00:22:51,900 --> 00:22:54,830
is actually covalently
linked to the amino group.

444
00:22:54,830 --> 00:22:57,920
And, that also has implications
for the structure of proteins

445
00:22:57,920 --> 00:23:00,580
because this particular
amino acid, whenever

446
00:23:00,580 --> 00:23:03,500
it occurs within a
polypeptide chain,

447
00:23:03,500 --> 00:23:06,760
doesn't have the flexibility of
assuming certain configurations

448
00:23:06,760 --> 00:23:10,630
that the other ones have
whose four side chains are not

449
00:23:10,630 --> 00:23:12,490
so encumbered.

450
00:23:12,490 --> 00:23:14,150
None of them has
total flexibility,

451
00:23:14,150 --> 00:23:16,380
but this one is
far more encumbered

452
00:23:16,380 --> 00:23:19,160
in the kinds of
three-dimensional structures

453
00:23:19,160 --> 00:23:21,520
that it can assume.

454
00:23:21,520 --> 00:23:26,050
And, with that in mind,
we begin to ask questions

455
00:23:26,050 --> 00:23:29,510
about how polypeptide
chains assume

456
00:23:29,510 --> 00:23:31,500
three-dimensional structure.

457
00:23:31,500 --> 00:23:36,570
If we talk about a polypeptide
chain, in our minds,

458
00:23:36,570 --> 00:23:41,285
hopefully, there's
only 28 combinations.

459
00:23:44,400 --> 00:23:46,410
Oh, am I good or what?

460
00:23:46,410 --> 00:23:50,340
Anyhow, all right,
so, look here.

461
00:23:50,340 --> 00:23:55,170
And here, you see, this is
a typical polypeptide chain.

462
00:23:55,170 --> 00:23:57,570
Here, we have a
three letter code.

463
00:23:57,570 --> 00:23:59,990
In truth, there is
a single letter code

464
00:23:59,990 --> 00:24:02,480
which was introduced
around 1965.

465
00:24:02,480 --> 00:24:07,090
So, each of the 20 amino acids
has its own single letter code.

466
00:24:07,090 --> 00:24:13,020
And, to make a frank and
depressing admission, 35 years,

467
00:24:13,020 --> 00:24:15,430
40 years after the
single amino acid letter

468
00:24:15,430 --> 00:24:18,845
code was instituted, I
still haven't learned it.

469
00:24:18,845 --> 00:24:20,720
But, we could learn
these three letter codes,

470
00:24:20,720 --> 00:24:23,760
which fortunately
are present here.

471
00:24:23,760 --> 00:24:25,820
In the single letter
code L is lucine,

472
00:24:25,820 --> 00:24:31,580
and A is alanine,
see, they know it.

473
00:24:31,580 --> 00:24:33,130
This is another
example of not being

474
00:24:33,130 --> 00:24:35,860
able to teach old
dogs new tricks.

475
00:24:35,860 --> 00:24:39,710
Anyhow, so here we
see the way, one way

476
00:24:39,710 --> 00:24:44,060
by which one might depict
an amino acid chain,

477
00:24:44,060 --> 00:24:45,250
a polypeptide chain.

478
00:24:45,250 --> 00:24:49,490
And keep in mind, this
can go on indefinitely.

479
00:24:49,490 --> 00:24:52,140
As we begin to wrestle with
the three-dimensional structure

480
00:24:52,140 --> 00:24:54,700
of the chain, we begin
to realize the following,

481
00:24:54,700 --> 00:24:58,700
and that is that after the
chain is initially synthesized,

482
00:24:58,700 --> 00:25:00,720
it's initially chaotic.

483
00:25:00,720 --> 00:25:03,330
And, as it extends,
it increasingly

484
00:25:03,330 --> 00:25:09,110
begins to assume a very specific
three-dimensional molecular

485
00:25:09,110 --> 00:25:11,440
configuration which is
indicated down here.

486
00:25:11,440 --> 00:25:14,910
So, the chaos that
operates initially

487
00:25:14,910 --> 00:25:19,570
will eventually result in a
native configuration over here,

488
00:25:19,570 --> 00:25:22,610
which in many respects
often represents the lowest

489
00:25:22,610 --> 00:25:24,810
free energy state.

490
00:25:24,810 --> 00:25:28,250
Since for the last 40 years,
people have been trying

491
00:25:28,250 --> 00:25:31,100
to figure out, if you knew the
amino acid sequence of this

492
00:25:31,100 --> 00:25:35,270
primary polypeptide here, if
you knew its primary structure,

493
00:25:35,270 --> 00:25:37,320
and when I say,
?primary structure,?

494
00:25:37,320 --> 00:25:39,965
what I mean is the sequence
of the amino acids.

495
00:25:39,965 --> 00:25:42,340
So, if you knew the primary
structure of the amino acids,

496
00:25:42,340 --> 00:25:45,840
you should, in principle, be
able to develop a computer

497
00:25:45,840 --> 00:25:48,310
algorithm that would predict
the three-dimensional

498
00:25:48,310 --> 00:25:51,530
configuration, which is shown
here in a very schematic way,

499
00:25:51,530 --> 00:25:54,930
and which we will discuss in
much greater detail shortly.

500
00:25:54,930 --> 00:25:57,580
And, the fact is, after
40 years of trying,

501
00:25:57,580 --> 00:26:00,480
one still is unable
to do that, i.e.,

502
00:26:00,480 --> 00:26:04,210
if I were to give the
primary amino acid

503
00:26:04,210 --> 00:26:07,330
sequence of the
polypeptide to the smartest

504
00:26:07,330 --> 00:26:10,550
biochemists in the world, and
there are some very smart ones,

505
00:26:10,550 --> 00:26:12,560
he or she could
still not tell me

506
00:26:12,560 --> 00:26:14,110
what the three-dimensional
structure

507
00:26:14,110 --> 00:26:18,261
of this protein with
total certainty would be.

508
00:26:18,261 --> 00:26:18,760
Why?

509
00:26:18,760 --> 00:26:21,320
Because there's an
almost infinite number

510
00:26:21,320 --> 00:26:24,550
of intramolecular
interactions that greatly

511
00:26:24,550 --> 00:26:29,760
complicate how the protein
assumes the structure.

512
00:26:29,760 --> 00:26:32,530
Moreover, if we talk about
this as the native state

513
00:26:32,530 --> 00:26:35,870
of the protein, we can imagine
that there?s ways of disrupting

514
00:26:35,870 --> 00:26:38,840
that because much of this
native state is created

515
00:26:38,840 --> 00:26:42,360
by intramolecular
hydrogen bonds.

516
00:26:42,360 --> 00:26:44,700
Remember, the hydrogen
bonds are relatively weak,

517
00:26:44,700 --> 00:26:49,070
and if we heat up
the temperature,

518
00:26:49,070 --> 00:26:51,120
then we can break
hydrogen bonds.

519
00:26:51,120 --> 00:26:55,650
And therefore, every time
we fry an egg, for example,

520
00:26:55,650 --> 00:26:58,300
if we want to get down
to Earth, we denature.

521
00:26:58,300 --> 00:27:02,000
We break up the native
three-dimensional structure

522
00:27:02,000 --> 00:27:05,360
of the albumin molecules that
constitute the egg white.

523
00:27:05,360 --> 00:27:07,640
And so, when everything
turns white, what we've done

524
00:27:07,640 --> 00:27:10,880
is to take a native molecule
like this, heated it

525
00:27:10,880 --> 00:27:13,700
up to temperatures
where the intramolecular

526
00:27:13,700 --> 00:27:16,130
bonds no longer stabilize.

527
00:27:16,130 --> 00:27:17,670
Notably, hydrogen
bonds no longer

528
00:27:17,670 --> 00:27:20,130
stabilize this
three-dimensional configuration,

529
00:27:20,130 --> 00:27:23,480
and we put it into a
denatured state, which

530
00:27:23,480 --> 00:27:26,450
might be all the way up here.

531
00:27:26,450 --> 00:27:30,960
And, therefore, this acquisition
of a native configuration,

532
00:27:30,960 --> 00:27:35,350
or a native state, native
representing the natural state,

533
00:27:35,350 --> 00:27:38,830
is also reversible
in many molecules

534
00:27:38,830 --> 00:27:40,710
simply by heating them up.

535
00:27:40,710 --> 00:27:42,750
There are to be sure yet
other molecules which

536
00:27:42,750 --> 00:27:45,290
are different from the egg
white from the albumin in egg

537
00:27:45,290 --> 00:27:47,310
white where if you
cool them back down,

538
00:27:47,310 --> 00:27:50,960
they will spontaneously
reassume their native structure.

539
00:27:50,960 --> 00:27:54,360
Many proteins, most,
will not do so.

540
00:27:54,360 --> 00:27:57,450
Well, again, let's go back to
this issue of the acquisition

541
00:27:57,450 --> 00:27:59,720
of complex,
three-dimensional structure.

542
00:27:59,720 --> 00:28:04,590
And here, we begin to see
how some of this structure

543
00:28:04,590 --> 00:28:08,650
is acquired and stabilized
through these intramolecular

544
00:28:08,650 --> 00:28:09,810
hydrogen bonds.

545
00:28:09,810 --> 00:28:12,650
And there are many opportunities
for these intramolecular

546
00:28:12,650 --> 00:28:15,740
hydrogen bonds because here we
see one polypeptide chain here,

547
00:28:15,740 --> 00:28:17,200
here we see another.

548
00:28:17,200 --> 00:28:20,780
And, we see that the NH2
group right here, I'm sorry,

549
00:28:20,780 --> 00:28:24,440
the nitrogen group here
with the proton side chain,

550
00:28:24,440 --> 00:28:28,740
and the carbonyl group here with
the oxygen are not encumbered.

551
00:28:28,740 --> 00:28:31,860
They are, in principle,
available to form hydrogen

552
00:28:31,860 --> 00:28:35,900
bonds with a polypeptide
chain somewhere else.

553
00:28:35,900 --> 00:28:37,770
Now, this other
polypeptide chain

554
00:28:37,770 --> 00:28:39,790
could once again be
from another protein,

555
00:28:39,790 --> 00:28:41,450
from another polypeptide.

556
00:28:41,450 --> 00:28:44,300
But more often than
not, we are once again

557
00:28:44,300 --> 00:28:49,090
dealing with
intramolecular cross-links.

558
00:28:49,090 --> 00:28:51,330
But in this case, the
intramolecular cross-links

559
00:28:51,330 --> 00:28:54,060
are not disulfide bonds
which are covalent,

560
00:28:54,060 --> 00:28:58,080
and hard and stable as a rock in
the absence of reducing agents.

561
00:28:58,080 --> 00:29:01,090
Here, we're talking about much
weaker bonds, hydrogen bonds

562
00:29:01,090 --> 00:29:07,080
which also act between
different loops of the protein

563
00:29:07,080 --> 00:29:09,880
and serve, once
again, to stabilize

564
00:29:09,880 --> 00:29:12,510
the three-dimensional
structure, the native state

565
00:29:12,510 --> 00:29:14,180
of the protein.

566
00:29:14,180 --> 00:29:16,880
And, you can see how these
opportunities for forming

567
00:29:16,880 --> 00:29:18,900
multiple hydrogen
bonds can create

568
00:29:18,900 --> 00:29:22,840
an enormous degree of stability.

569
00:29:22,840 --> 00:29:25,730
And, here are some
examples of what we now

570
00:29:25,730 --> 00:29:29,450
call the secondary
structure of the protein.

571
00:29:29,450 --> 00:29:32,510
Just a second ago, or several
minutes ago to be honest,

572
00:29:32,510 --> 00:29:35,590
and I'm always honest
with you, class,

573
00:29:35,590 --> 00:29:39,000
the primary structure is
the amino acid sequence.

574
00:29:39,000 --> 00:29:41,080
The secondary
structure represents

575
00:29:41,080 --> 00:29:42,760
configurations like this.

576
00:29:42,760 --> 00:29:46,120
Here is an alpha helix.

577
00:29:46,120 --> 00:29:49,370
Here is a beta pleated sheet.

578
00:29:49,370 --> 00:29:51,250
And, what we see here
in this alpha helix

579
00:29:51,250 --> 00:29:55,000
is we have a helical structure
where the amine group down

580
00:29:55,000 --> 00:29:58,630
here, the NH group, hydrogen
bonds with a residue that is,

581
00:29:58,630 --> 00:30:00,900
I think, three and a
half residues upstream,

582
00:30:00,900 --> 00:30:04,680
one, two, there's an
amine down there, so,

583
00:30:04,680 --> 00:30:07,420
with the carbonyl group that's
three and a half residues

584
00:30:07,420 --> 00:30:08,920
upstream of it.

585
00:30:08,920 --> 00:30:12,230
This one, once again, reaches
three and a half residues

586
00:30:12,230 --> 00:30:13,020
upstream.

587
00:30:13,020 --> 00:30:16,150
Not all the hydrogen bonds
are shown in the background.

588
00:30:16,150 --> 00:30:18,520
Only the ones on our
side of the helix

589
00:30:18,520 --> 00:30:20,410
are shown, on the front
side of the helix.

590
00:30:20,410 --> 00:30:23,360
But, you can imagine that
this can perpetuate itself.

591
00:30:23,360 --> 00:30:25,390
And, each of these
carbonyl's may

592
00:30:25,390 --> 00:30:29,080
associate with a proton,
an NH group that's

593
00:30:29,080 --> 00:30:32,280
either above or below
that particular residue.

594
00:30:32,280 --> 00:30:35,540
And this, in turn, can
create a helical structure.

595
00:30:35,540 --> 00:30:38,670
By the way, proline
doesn't fit well.

596
00:30:38,670 --> 00:30:41,750
If you add a proline
in here, proline

597
00:30:41,750 --> 00:30:45,411
is known in the trade
as a helix breaker.

598
00:30:45,411 --> 00:30:45,910
Why?

599
00:30:45,910 --> 00:30:49,860
Because it cannot twist itself
around to form an alpha helix.

600
00:30:49,860 --> 00:30:51,970
And so, if the
primary amino acid

601
00:30:51,970 --> 00:30:54,800
were to dictate that a proline
would be inserted right

602
00:30:54,800 --> 00:30:57,210
here, for example,
then this helix

603
00:30:57,210 --> 00:31:00,070
might exist down
below and above,

604
00:31:00,070 --> 00:31:02,680
but it would not be continuous
because the presence

605
00:31:02,680 --> 00:31:06,020
of a proline is highly
disruptive of the formation

606
00:31:06,020 --> 00:31:09,254
of an alpha helix.

607
00:31:09,254 --> 00:31:10,670
This means that,
in principle, you

608
00:31:10,670 --> 00:31:13,410
can make some predictions
about the localized

609
00:31:13,410 --> 00:31:16,190
structure of a polypeptide
by knowing whether or not

610
00:31:16,190 --> 00:31:18,130
proline is present, for example.

611
00:31:18,130 --> 00:31:19,960
But that still doesn't
give you the power

612
00:31:19,960 --> 00:31:22,720
to predict the entire
three-dimensional structure

613
00:31:22,720 --> 00:31:25,620
of the finished protein itself.

614
00:31:25,620 --> 00:31:29,060
Now, let's agree that this
is the secondary structure

615
00:31:29,060 --> 00:31:32,080
of the protein, i.e., the
various domains which often

616
00:31:32,080 --> 00:31:35,740
form alpha helices within a
certain segment of the protein

617
00:31:35,740 --> 00:31:37,890
or a certain segment
of the protein

618
00:31:37,890 --> 00:31:39,700
will form beta pleated sheets.

619
00:31:39,700 --> 00:31:42,120
And there are several
other less common kinds

620
00:31:42,120 --> 00:31:44,890
of secondary structure.

621
00:31:44,890 --> 00:31:48,260
And here, we deal with
tertiary structure.

622
00:31:48,260 --> 00:31:50,220
Now we are getting
really interesting.

623
00:31:50,220 --> 00:31:51,740
Or, maybe you don't like it.

624
00:31:51,740 --> 00:31:54,120
But some people say
it's really interesting

625
00:31:54,120 --> 00:31:57,610
because here are the tertiary
structures of some arbitrarily

626
00:31:57,610 --> 00:31:59,930
chosen proteins.

627
00:31:59,930 --> 00:32:04,140
Here, the tertiary structure
of this particular protein,

628
00:32:04,140 --> 00:32:08,880
and the identities of these
are not given in our textbook.

629
00:32:08,880 --> 00:32:10,766
And, I'm sure if we
spent two or three weeks,

630
00:32:10,766 --> 00:32:12,140
we could find out
what they were.

631
00:32:12,140 --> 00:32:15,920
But anyhow, here is a protein,
a three-dimensional structure

632
00:32:15,920 --> 00:32:20,960
of a protein which is composed
of four alpha helices which

633
00:32:20,960 --> 00:32:22,510
go up.

634
00:32:22,510 --> 00:32:26,410
Another alpha helix, alpha
helix, alpha helix, alpha

635
00:32:26,410 --> 00:32:28,630
helix, they are depicted
here, fortunately,

636
00:32:28,630 --> 00:32:30,580
in four different colors.

637
00:32:30,580 --> 00:32:33,280
And so, we see that what we
talk about tertiary structure,

638
00:32:33,280 --> 00:32:36,980
we're talking about how the
alpha helices are disposed

639
00:32:36,980 --> 00:32:39,070
with respect to one another.

640
00:32:39,070 --> 00:32:41,070
The primary structure of
the amino acid sequence

641
00:32:41,070 --> 00:32:42,410
is not shown here.

642
00:32:42,410 --> 00:32:45,240
The secondary structure
represents these individual

643
00:32:45,240 --> 00:32:48,970
alpha helices, and the tertiary
structure represents how these

644
00:32:48,970 --> 00:32:51,710
alpha helices are arranged
vis-?-vis one another.

645
00:32:51,710 --> 00:32:55,430
Here is a protein which is
structured much differently.

646
00:32:58,420 --> 00:33:02,310
It's formed of many
beta pleated sheets.

647
00:33:02,310 --> 00:33:05,310
We saw that in the last
figure, in the last overhead.

648
00:33:05,310 --> 00:33:08,300
You see it as a quite different
overall three-dimensional

649
00:33:08,300 --> 00:33:09,790
structure.

650
00:33:09,790 --> 00:33:12,210
This could be the beginning
of an alpha helix down here,

651
00:33:12,210 --> 00:33:14,560
although that's quite equivocal.

652
00:33:14,560 --> 00:33:16,200
And here, we see
yet another point.

653
00:33:16,200 --> 00:33:19,230
And that is, as we said
before, the tertiary structure

654
00:33:19,230 --> 00:33:23,620
independent of these alpha
helices and beta pleated sheets

655
00:33:23,620 --> 00:33:28,420
may be stabilized by these
covalent inter-strand

656
00:33:28,420 --> 00:33:31,650
cross-links formed
by the cystines.

657
00:33:31,650 --> 00:33:33,800
And in the end, if we
put all that together,

658
00:33:33,800 --> 00:33:36,360
then we come to the realization
that the three-dimensional

659
00:33:36,360 --> 00:33:40,100
structure of a protein as
determined by the art of x-ray

660
00:33:40,100 --> 00:33:47,190
-- There we go.

661
00:33:47,190 --> 00:33:49,940
I'm not actually dyslexic.

662
00:33:49,940 --> 00:33:52,250
I actually have a cousin
who I won't mention

663
00:33:52,250 --> 00:33:54,650
whose son was so dyslexic
that when he came to stairways

664
00:33:54,650 --> 00:33:56,910
he didn't know whether to
put his foot up or down.

665
00:33:56,910 --> 00:33:58,010
Now that's difficulty.

666
00:33:58,010 --> 00:34:00,660
This is not so bad.

667
00:34:00,660 --> 00:34:03,970
OK, anyhow, because I solved
it within less than two minutes

668
00:34:03,970 --> 00:34:05,614
time, all right,
so here we see this

669
00:34:05,614 --> 00:34:07,780
is what the three-dimensional
structure of a protein

670
00:34:07,780 --> 00:34:08,690
looks like.

671
00:34:08,690 --> 00:34:10,610
This is called a
space-filling model

672
00:34:10,610 --> 00:34:12,969
because here, one
draws in, as determined

673
00:34:12,969 --> 00:34:15,050
by x-ray crystallography
what the,

674
00:34:15,050 --> 00:34:16,670
if we could see
what a protein looks

675
00:34:16,670 --> 00:34:18,409
like, what it actually
must look like,

676
00:34:18,409 --> 00:34:22,760
where each of the atoms
including these side chains

677
00:34:22,760 --> 00:34:24,270
is actually depicted.

678
00:34:24,270 --> 00:34:28,832
Before, when we used these far
more schematic descriptions

679
00:34:28,832 --> 00:34:31,290
like here, we were just talking
about the overall structure

680
00:34:31,290 --> 00:34:31,956
of the backbone.

681
00:34:31,956 --> 00:34:35,739
We weren't really indicating
where the side chains were,

682
00:34:35,739 --> 00:34:37,616
and what space
they would fill up.

683
00:34:37,616 --> 00:34:39,199
And, if we give them
the chance, if we

684
00:34:39,199 --> 00:34:42,190
put in all of the other
atoms, the side chains,

685
00:34:42,190 --> 00:34:45,670
and we create a
space-filling model where

686
00:34:45,670 --> 00:34:48,320
the actual atoms
are shown, this is

687
00:34:48,320 --> 00:34:50,290
what the protein
would look like.

688
00:34:50,290 --> 00:34:53,300
And the fact of the matter is
that all virtually proteins

689
00:34:53,300 --> 00:34:55,710
have very specific structures.

690
00:34:55,710 --> 00:34:58,670
It's not as if they can shift
from one structure to another.

691
00:34:58,670 --> 00:35:01,140
Once they leave their
normal native structure

692
00:35:01,140 --> 00:35:07,910
they will lose their ability to
do what their normal jobs are.

693
00:35:07,910 --> 00:35:10,980
And, this particular
overhead happens

694
00:35:10,980 --> 00:35:12,660
to bring in yet another
theme that we're

695
00:35:12,660 --> 00:35:14,720
going to focus on
increasingly, which

696
00:35:14,720 --> 00:35:17,440
is, what do proteins
do in cells?

697
00:35:17,440 --> 00:35:19,160
I'm glad I asked that question.

698
00:35:19,160 --> 00:35:23,320
One of the things they do is
they act as catalysts, i.e. ,

699
00:35:23,320 --> 00:35:25,290
as enzymes.

700
00:35:25,290 --> 00:35:27,860
The fact is, as we
will discuss later,

701
00:35:27,860 --> 00:35:30,690
virtually all
biochemical reactions

702
00:35:30,690 --> 00:35:35,530
require an enzyme catalyst in
order to propel them forward.

703
00:35:35,530 --> 00:35:38,590
That is to say, if there's a
biochemical reaction to occur,

704
00:35:38,590 --> 00:35:41,860
almost always it will
not occur spontaneously

705
00:35:41,860 --> 00:35:44,360
the same way that a
hydroxyl ion and a hydrogen

706
00:35:44,360 --> 00:35:46,890
will join together
spontaneously in water.

707
00:35:46,890 --> 00:35:50,930
Almost all biochemical
reactions require the mediation

708
00:35:50,930 --> 00:35:56,550
of an enzyme which is a
biological catalyst in order

709
00:35:56,550 --> 00:35:58,510
to encourage this to happen.

710
00:35:58,510 --> 00:36:05,860
And, almost all catalysts
in our cells are proteins.

711
00:36:05,860 --> 00:36:11,820
So, if you have 4,326 distinct
biochemical reactions occurring

712
00:36:11,820 --> 00:36:14,110
in the cell, that means
that there's probably

713
00:36:14,110 --> 00:36:16,830
almost as many distinct
enzymes, each one of which

714
00:36:16,830 --> 00:36:19,800
is assigned to
mediate one or another

715
00:36:19,800 --> 00:36:22,790
of those distinct
biochemical reactions.

716
00:36:22,790 --> 00:36:24,400
And here, we see
the fact that this

717
00:36:24,400 --> 00:36:28,510
is an enzyme which happens
to be called hexokinase.

718
00:36:28,510 --> 00:36:31,160
Recall that the -ase
suffix at the end

719
00:36:31,160 --> 00:36:34,270
dictates that this is
already an enzyme rather

720
00:36:34,270 --> 00:36:35,850
than a carbohydrate.

721
00:36:35,850 --> 00:36:41,200
And, this attaches, in fact, a
phosphate group onto glucose.

722
00:36:41,200 --> 00:36:43,800
And, what happens is
that the glucose, which

723
00:36:43,800 --> 00:36:47,090
is the substrate, which is
acted upon by the catalyst,

724
00:36:47,090 --> 00:36:51,330
is pulled into this site
in the protein which

725
00:36:51,330 --> 00:36:56,570
is highly specialized to
mediate the enzymatic reaction.

726
00:36:56,570 --> 00:36:59,270
Almost all the business
of this complex enzyme

727
00:36:59,270 --> 00:37:01,930
is carried out right here.

728
00:37:01,930 --> 00:37:04,210
And somehow, a lot of
the other amino acids

729
00:37:04,210 --> 00:37:06,900
that are located at a distance
are doing other things

730
00:37:06,900 --> 00:37:09,670
like regulating the
activity of the enzyme.

731
00:37:09,670 --> 00:37:11,700
But the actual business
end of the enzyme

732
00:37:11,700 --> 00:37:16,720
is present in what is called a
catalytic cleft, an active site

733
00:37:16,720 --> 00:37:19,360
of this enzyme in which the
substrates are pulled in

734
00:37:19,360 --> 00:37:22,360
and are manipulated
and changed chemically

735
00:37:22,360 --> 00:37:26,470
by the actions of this
particular enzyme.

736
00:37:26,470 --> 00:37:31,180
Now, in saying that virtually
all catalysts, but not all, are

737
00:37:31,180 --> 00:37:35,050
proteins, I also mean
to say that proteins

738
00:37:35,050 --> 00:37:37,810
have a second major
function in the body.

739
00:37:37,810 --> 00:37:41,010
The first major function is to
act as enzymes in catalysts.

740
00:37:41,010 --> 00:37:45,450
The second major function is to
create biochemical structures,

741
00:37:45,450 --> 00:37:49,560
i.e., structures of different
cytoskeleton proteins such as I

742
00:37:49,560 --> 00:37:53,580
showed you two lectures ago.

743
00:37:53,580 --> 00:37:55,990
And so, we are going to come
repeatedly to the situations

744
00:37:55,990 --> 00:37:59,160
where complex structural
entities in the cell

745
00:37:59,160 --> 00:38:02,650
are composed of different
structural proteins.

746
00:38:02,650 --> 00:38:04,590
Again, this is just
a prelude to talking

747
00:38:04,590 --> 00:38:07,530
about these in greater details,
these two major functions

748
00:38:07,530 --> 00:38:09,900
of enzymatic catalysis
on the one hand,

749
00:38:09,900 --> 00:38:13,280
and creating structure
on the other hand.

750
00:38:13,280 --> 00:38:17,550
And so now, we get to really
four hierarchical levels

751
00:38:17,550 --> 00:38:20,590
of protein structure.

752
00:38:20,590 --> 00:38:25,980
The primary structure is
the amino acid sequence.

753
00:38:25,980 --> 00:38:29,140
And, if we dwell for second
on this amino acid sequence,

754
00:38:29,140 --> 00:38:32,270
let's realize that any
single amino acid can

755
00:38:32,270 --> 00:38:34,340
follow any other amino acid.

756
00:38:34,340 --> 00:38:36,870
So, what that means
is that if glycine

757
00:38:36,870 --> 00:38:39,360
is the first amino acid,
as it happens to be here,

758
00:38:39,360 --> 00:38:42,290
serine is only one of
20 different possible

759
00:38:42,290 --> 00:38:44,300
second amino acids.

760
00:38:44,300 --> 00:38:50,910
Aspartic acid is only one of
20 different third amino acids

761
00:38:50,910 --> 00:38:52,870
as the third residue.

762
00:38:52,870 --> 00:38:54,700
We often call these
different residues:

763
00:38:54,700 --> 00:38:57,170
the first residue, second
residue, third residue,

764
00:38:57,170 --> 00:38:59,460
fourth residue, and
fourth, and so forth.

765
00:38:59,460 --> 00:39:01,410
And, keep in mind,
if we think about

766
00:39:01,410 --> 00:39:04,050
the combinatorial
implications of that,

767
00:39:04,050 --> 00:39:07,070
the first amino acid residue
can have 20 different ones.

768
00:39:07,070 --> 00:39:09,260
The second can have 20
different identities.

769
00:39:09,260 --> 00:39:11,060
The third can have 20
different identities.

770
00:39:11,060 --> 00:39:15,590
That means if we
make a tripeptide

771
00:39:15,590 --> 00:39:18,600
- a tripeptide has
three amino acids in it.

772
00:39:18,600 --> 00:39:21,980
That means we can make
400 dipeptides, 400

773
00:39:21,980 --> 00:39:26,100
distinct dipeptides,
and we can make

774
00:39:26,100 --> 00:39:29,880
8,000 distinct tripeptides.

775
00:39:29,880 --> 00:39:34,620
Now, if you imagine that
the average amino acid,

776
00:39:34,620 --> 00:39:36,890
the average protein
in the cell is,

777
00:39:36,890 --> 00:39:39,970
let's say, 150 amino
acid residues long,

778
00:39:39,970 --> 00:39:45,660
that means that in
principle, one could make 20

779
00:39:45,660 --> 00:39:51,960
to the 150th power distinct
amino acid sequences because

780
00:39:51,960 --> 00:39:53,580
of these absence
of any constraints

781
00:39:53,580 --> 00:39:56,820
of which amino acid will
follow which other amino acids.

782
00:39:56,820 --> 00:40:01,820
In other words, if the
average polypeptide

783
00:40:01,820 --> 00:40:03,770
has this many residues,
this is the number

784
00:40:03,770 --> 00:40:07,260
of distinct 150 amino
acid residue long proteins

785
00:40:07,260 --> 00:40:10,131
that one could, in
principle, synthesize.

786
00:40:10,131 --> 00:40:11,630
I'm not saying all
of them have ever

787
00:40:11,630 --> 00:40:14,390
been synthesized since
the formation of life

788
00:40:14,390 --> 00:40:15,400
on this planet.

789
00:40:15,400 --> 00:40:21,260
Indeed, since some amino
acid chains are 4, 5, 600,

790
00:40:21,260 --> 00:40:24,970
even 2,000 amino
acid residues long,

791
00:40:24,970 --> 00:40:27,450
I think the one that is
affecting muscular dystrophy

792
00:40:27,450 --> 00:40:29,490
is more than 2,000 amino acids.

793
00:40:29,490 --> 00:40:30,000
Dystrophin.

794
00:40:30,000 --> 00:40:31,230
Does anybody know here?

795
00:40:31,230 --> 00:40:32,250
It's big.

796
00:40:32,250 --> 00:40:35,360
Anyhow, imagine the
number of possibilities.

797
00:40:35,360 --> 00:40:38,350
So, combinatorially,
life can make almost

798
00:40:38,350 --> 00:40:42,850
whatever types of amino acids
it would like by dictating

799
00:40:42,850 --> 00:40:44,580
the sequence of amino acids.

800
00:40:44,580 --> 00:40:48,390
Now, let's just go
and look here again.

801
00:40:48,390 --> 00:40:50,070
There is a secondary structure.

802
00:40:50,070 --> 00:40:51,950
The tertiary
structure is the way

803
00:40:51,950 --> 00:40:54,620
in which the different
alpha helices here

804
00:40:54,620 --> 00:40:57,450
or beta pleated sheets are
disposed three-dimensionally

805
00:40:57,450 --> 00:40:59,290
with respect to one another.

806
00:40:59,290 --> 00:41:02,490
And, the quaternary
structure represents

807
00:41:02,490 --> 00:41:07,570
how different polypeptides are
associated one with the other.

808
00:41:07,570 --> 00:41:11,330
So, for example,
hemoglobin is a tetramer.

809
00:41:11,330 --> 00:41:13,980
Hemoglobin doesn't exist
as a monomeric protein.

810
00:41:13,980 --> 00:41:15,760
Its solution exists
as a tetramer.

811
00:41:15,760 --> 00:41:18,400
And there's two kinds
of globin chains.

812
00:41:18,400 --> 00:41:21,620
There is an alpha
kind and a beta kind.

813
00:41:21,620 --> 00:41:24,170
And, if we look in a very rough
and schematic way at the way

814
00:41:24,170 --> 00:41:26,750
that a hemoglobin
tetramer is arranged,

815
00:41:26,750 --> 00:41:30,460
there are two alpha polypeptide
chains and two beta polypeptide

816
00:41:30,460 --> 00:41:31,440
chains.

817
00:41:31,440 --> 00:41:33,979
They are not covalently
attached to one another.

818
00:41:33,979 --> 00:41:36,270
They are associated with one
another via hydrogen bonds

819
00:41:36,270 --> 00:41:38,310
and hydrophobic interactions.

820
00:41:38,310 --> 00:41:40,960
And, this is the actual
native configuration

821
00:41:40,960 --> 00:41:44,210
of globin to alpha
and to beta chains.

822
00:41:44,210 --> 00:41:46,750
It doesn't exist as a single
amino acid in solution.

823
00:41:46,750 --> 00:41:48,260
It exists as a tetramer.

824
00:41:48,260 --> 00:41:50,620
And, indeed, most, or
I shouldn't say most,

825
00:41:50,620 --> 00:41:55,300
but very many proteins exist
in these configurations

826
00:41:55,300 --> 00:41:59,280
where the tertiary
structure represents

827
00:41:59,280 --> 00:42:01,950
four different
amino acid chains.

828
00:42:01,950 --> 00:42:05,010
And each of these has
an N and C terminal.

829
00:42:05,010 --> 00:42:06,960
Each of these is
chemically distinct.

830
00:42:06,960 --> 00:42:09,890
These four could probably be
taken apart from one another

831
00:42:09,890 --> 00:42:12,050
simply by raising
the temperature.

832
00:42:12,050 --> 00:42:13,710
And, they associate like this.

833
00:42:13,710 --> 00:42:15,902
And, in the absence
of this association,

834
00:42:15,902 --> 00:42:18,360
if you just had one of these
alphas, or one of these betas,

835
00:42:18,360 --> 00:42:20,170
it wouldn't function
well at all.

836
00:42:20,170 --> 00:42:23,570
In fact, it might be
totally dysfunctional.

837
00:42:23,570 --> 00:42:26,350
One other thing that
may be implicit to you,

838
00:42:26,350 --> 00:42:29,180
but I haven't said, but that
is very important to realize

839
00:42:29,180 --> 00:42:31,947
is the following:
Let's imagine that this

840
00:42:31,947 --> 00:42:34,030
is the three-dimensional
structure of the protein,

841
00:42:34,030 --> 00:42:36,160
as it may well be.

842
00:42:36,160 --> 00:42:39,880
Let's now think about
hydrophobic and hydrophilic

843
00:42:39,880 --> 00:42:41,660
amino acids.

844
00:42:41,660 --> 00:42:44,720
The hydrophobic amino acids
hate to be present water.

845
00:42:44,720 --> 00:42:48,940
And therefore, they are, we can
imagine this case correctly,

846
00:42:48,940 --> 00:42:53,480
tucked away inside the
interstices of the protein

847
00:42:53,480 --> 00:42:56,030
far way from the surface.

848
00:42:56,030 --> 00:42:58,270
They don't have any
contact with water.

849
00:42:58,270 --> 00:43:01,940
Conversely, the highly charged
hydrophilic amino acids

850
00:43:01,940 --> 00:43:05,230
are actually sticking
out at the surface.

851
00:43:05,230 --> 00:43:08,210
And this begins to yield
yet another insight

852
00:43:08,210 --> 00:43:11,680
into how the three-dimensional
stereochemistry of proteins

853
00:43:11,680 --> 00:43:15,390
is maintained and dictated
because the hydrophobic amino

854
00:43:15,390 --> 00:43:17,780
acids, through
hydrophobic interactions,

855
00:43:17,780 --> 00:43:20,900
stabilize the inner core
of the protein that is well

856
00:43:20,900 --> 00:43:23,760
shielded from the
aqueous solvent.

857
00:43:23,760 --> 00:43:26,080
The hydrophilic amino
acids are on the outside.

858
00:43:26,080 --> 00:43:29,490
They like to be in intimate
contact with the water.

859
00:43:29,490 --> 00:43:31,740
So, we already now have
talked about a number

860
00:43:31,740 --> 00:43:35,240
of distinct different
interactions that

861
00:43:35,240 --> 00:43:37,870
are responsible for creating
the three-dimensional

862
00:43:37,870 --> 00:43:40,280
stereochemistry of the protein.

863
00:43:40,280 --> 00:43:43,760
First of all, there are
the disulfide bonds,

864
00:43:43,760 --> 00:43:47,220
which create chain-to-chain
covalent interactions.

865
00:43:47,220 --> 00:43:51,630
They are the hydrogen bonds
in which different chains

866
00:43:51,630 --> 00:43:53,200
can interact one another.

867
00:43:53,200 --> 00:43:56,370
And there are these hydrophobic
and hydrophilic interactions.

868
00:43:56,370 --> 00:43:59,200
And, there are some relatively
inconsequential van der Waals

869
00:43:59,200 --> 00:44:00,702
interactions, which
are really not

870
00:44:00,702 --> 00:44:02,410
worth discussing
although some people get

871
00:44:02,410 --> 00:44:03,620
really excited about them.

872
00:44:03,620 --> 00:44:05,960
But we won't.

873
00:44:05,960 --> 00:44:10,120
So, here we now begin to see
that we have really interesting

874
00:44:10,120 --> 00:44:13,060
polypeptides unlike the
boring polypeptides that

875
00:44:13,060 --> 00:44:20,350
are ultimately the way one
must judge carbohydrates.

876
00:44:20,350 --> 00:44:22,290
Some people think
carbohydrate chemistry

877
00:44:22,290 --> 00:44:23,730
is really interesting.

878
00:44:23,730 --> 00:44:26,100
But it really isn't
that interesting

879
00:44:26,100 --> 00:44:29,870
because you just have the
same monomer in a hundred,

880
00:44:29,870 --> 00:44:31,370
or 500 stretches.

881
00:44:31,370 --> 00:44:33,230
Here, a protein is
much more interesting

882
00:44:33,230 --> 00:44:35,770
because of this
enormous variability

883
00:44:35,770 --> 00:44:39,570
in amino acid sequence,
and the consequent ability

884
00:44:39,570 --> 00:44:45,660
to create all kinds of chemical
reactivities and structures

885
00:44:45,660 --> 00:44:48,910
because of these 20
different amino acids.

886
00:44:48,910 --> 00:44:51,140
If we were to imagine
life on another planet,

887
00:44:51,140 --> 00:44:53,060
and we imagine that
there were, let's say,

888
00:44:53,060 --> 00:44:57,060
amino acid-like molecules
that were part of life,

889
00:44:57,060 --> 00:45:00,150
maybe that other life wouldn't
have exactly the same 20

890
00:45:00,150 --> 00:45:02,170
amino acids as we do.

891
00:45:02,170 --> 00:45:06,430
It almost certainly would be
a water base the way we are.

892
00:45:06,430 --> 00:45:10,100
But, it would also
rely on hydrogen bonds

893
00:45:10,100 --> 00:45:14,570
and hydrophilicity, and
hydrophobicity interactions

894
00:45:14,570 --> 00:45:17,740
in order to dictate the
three-dimensional structure.

895
00:45:17,740 --> 00:45:19,890
In the absence of
this very specific

896
00:45:19,890 --> 00:45:22,320
three-dimensional
structure I will tell you

897
00:45:22,320 --> 00:45:24,819
that this enzyme
could not function.

898
00:45:24,819 --> 00:45:26,360
And, if you were to
take this enzyme,

899
00:45:26,360 --> 00:45:29,540
if it were typical enzyme and
you were to heat it up briefly,

900
00:45:29,540 --> 00:45:33,400
even often slightly above
normal body temperature,

901
00:45:33,400 --> 00:45:36,040
it might denature,
i.e., it might

902
00:45:36,040 --> 00:45:40,860
lose its three-dimensional
structure irreversibly.

903
00:45:40,860 --> 00:45:46,530
And, once it was denatured,
this process of denaturation,

904
00:45:46,530 --> 00:45:49,400
it might not be able to
spontaneously reassume

905
00:45:49,400 --> 00:45:51,850
that pre-existing
three-dimensional configuration

906
00:45:51,850 --> 00:45:54,690
and therefore would
forever be inactive.

907
00:45:54,690 --> 00:45:56,590
That means to say
very explicitly

908
00:45:56,590 --> 00:45:58,650
that even though
the amino acids that

909
00:45:58,650 --> 00:46:02,850
are creating that active
catalytic site remain there.

910
00:46:02,850 --> 00:46:06,810
Their highly specific
three-dimensional disposition

911
00:46:06,810 --> 00:46:10,360
is critical for the continued
actions of this enzyme.

912
00:46:10,360 --> 00:46:13,840
And, once their
three-dimensional dispositions

913
00:46:13,840 --> 00:46:16,770
are shifted around through
the process of interactions,

914
00:46:16,770 --> 00:46:20,450
then, we have trouble because
the enzyme can no longer

915
00:46:20,450 --> 00:46:22,240
do its assigned task.

916
00:46:22,240 --> 00:46:27,480
We are going to go now to an
even higher order of complexity

917
00:46:27,480 --> 00:46:28,890
in one sense.

918
00:46:28,890 --> 00:46:32,180
We are going to go to the
royalty of the macromolecules,

919
00:46:32,180 --> 00:46:34,320
which are the nucleic acids.

920
00:46:34,320 --> 00:46:36,490
Of course, protein chemists
would take great umbrage

921
00:46:36,490 --> 00:46:39,510
at the very notion
that there are

922
00:46:39,510 --> 00:46:41,540
things better than proteins.

923
00:46:41,540 --> 00:46:44,440
But, the fact of
the matter is, I

924
00:46:44,440 --> 00:46:46,180
can't show you that
overhead because it's

925
00:46:46,180 --> 00:46:49,290
from the other textbook
which is copyright,

926
00:46:49,290 --> 00:46:50,724
and we are being filmed.

927
00:46:50,724 --> 00:46:52,140
How many people
have had the backs

928
00:46:52,140 --> 00:46:55,230
of their heads immortalized
on these videos?

929
00:46:55,230 --> 00:47:00,040
Did you call home and ask
anybody to identify you?

930
00:47:00,040 --> 00:47:04,440
I don't know, but
soon each of us

931
00:47:04,440 --> 00:47:07,140
has the limelight for 15
minutes a lifetime, right?

932
00:47:07,140 --> 00:47:09,330
So, you'll have your 15 minutes.

933
00:47:09,330 --> 00:47:11,740
Here are some nucleic acids.

934
00:47:11,740 --> 00:47:15,140
And let's look at these
nucleic acids and the way

935
00:47:15,140 --> 00:47:16,507
they are put together.

936
00:47:16,507 --> 00:47:19,090
Keep in mind to anticipate what
we are going to say next time,

937
00:47:19,090 --> 00:47:21,600
once again, we want to
make end-to-end aggregates.

938
00:47:21,600 --> 00:47:25,150
We want to polymerize molecules.

939
00:47:25,150 --> 00:47:29,160
And in this case, we
want to do so once again

940
00:47:29,160 --> 00:47:31,807
through a dehydration reaction.

941
00:47:31,807 --> 00:47:33,890
And, moreover, just to
look at the building blocks

942
00:47:33,890 --> 00:47:37,432
of nucleic acids, we start again
in this case with two pentoses.

943
00:47:37,432 --> 00:47:38,890
Recall that they
have fuor carbons:

944
00:47:38,890 --> 00:47:42,530
one, two, three,
four, did I say four?

945
00:47:42,530 --> 00:47:45,500
You know I meant five.

946
00:47:45,500 --> 00:47:47,030
One, two, three, four, five.

947
00:47:47,030 --> 00:47:48,530
So, whenever I say
four from now on,

948
00:47:48,530 --> 00:47:54,740
I mean, or, whenever I say
four I may also mean four.

949
00:47:54,740 --> 00:47:57,540
OK, one, two, three, four five.

950
00:47:57,540 --> 00:48:01,570
And let's look at the two basic
kinds of pentose molecules

951
00:48:01,570 --> 00:48:05,510
that are present in nucleic
acid because they define

952
00:48:05,510 --> 00:48:09,580
the essential difference
between DNA and RNA.

953
00:48:09,580 --> 00:48:12,310
Here's a regular old
rather familiar kind

954
00:48:12,310 --> 00:48:14,930
of pentose with five carbons.

955
00:48:14,930 --> 00:48:17,300
And here's an unfamiliar
kind of pentose

956
00:48:17,300 --> 00:48:19,430
which we call deoxyribose.

957
00:48:19,430 --> 00:48:20,270
Why?

958
00:48:20,270 --> 00:48:21,830
Because if you look
really carefully,

959
00:48:21,830 --> 00:48:23,496
you'll see that the
hydroxyl group here,

960
00:48:23,496 --> 00:48:26,590
which should be present in
any self-respecting pentose is

961
00:48:26,590 --> 00:48:30,330
missing, and is replaced simply
by a hydrogen group, i.e.,

962
00:48:30,330 --> 00:48:35,360
it's lost its oxygen, whence
cometh the word, ?deoxyribose,?

963
00:48:35,360 --> 00:48:39,770
and ultimately clearly the word,
?deoxyribose nucleic acid.?

964
00:48:39,770 --> 00:48:42,720
And one of the attributes,
one of the virtues

965
00:48:42,720 --> 00:48:45,000
of carbohydrates, as
we discussed last time,

966
00:48:45,000 --> 00:48:47,730
were these numerous
hydroxyl groups,

967
00:48:47,730 --> 00:48:51,970
which represent opportunities
for all kinds of dehydration

968
00:48:51,970 --> 00:48:54,690
reactions which can
enable one to build

969
00:48:54,690 --> 00:48:56,920
much more complex molecules.

970
00:48:56,920 --> 00:49:00,110
And here, we see the
structure of, for example,

971
00:49:00,110 --> 00:49:04,450
a deoxyribonucleotide
whose detailed structure

972
00:49:04,450 --> 00:49:06,660
we'll get into next time.

973
00:49:06,660 --> 00:49:08,890
But just, let's look at
how these hydroxyl groups

974
00:49:08,890 --> 00:49:09,940
have been used.

975
00:49:09,940 --> 00:49:12,340
The hydroxyl group,
in this case in DNA,

976
00:49:12,340 --> 00:49:17,600
and by the way notice that
the structure I've shown here,

977
00:49:17,600 --> 00:49:19,960
there's a side
chain attached here,

978
00:49:19,960 --> 00:49:21,650
and a side chain attached here.

979
00:49:21,650 --> 00:49:23,900
And neither of those
depends on whether or not

980
00:49:23,900 --> 00:49:27,360
there is a hydrogen or
a hydroxyl right here.

981
00:49:27,360 --> 00:49:29,090
And look at what's
happened here.

982
00:49:29,090 --> 00:49:32,390
Here, we have this
hydroxyl over here

983
00:49:32,390 --> 00:49:35,070
to which a base has been
attached covalently,

984
00:49:35,070 --> 00:49:37,950
once again, by a
dehydration reaction.

985
00:49:37,950 --> 00:49:41,660
And here, we have a situation
where actually three phosphate

986
00:49:41,660 --> 00:49:44,050
groups have been attached
to the hydroxyl group

987
00:49:44,050 --> 00:49:46,320
in this direction.

988
00:49:46,320 --> 00:49:48,530
And, this represents the
basic building blocks

989
00:49:48,530 --> 00:49:50,084
of nucleic acids.

990
00:49:50,084 --> 00:49:52,500
Now, one of the things that's
going to be really important

991
00:49:52,500 --> 00:49:54,270
and that you're going to have
to memorize, I told you, you

992
00:49:54,270 --> 00:49:56,320
weren't going to have
to memorize anything.

993
00:49:56,320 --> 00:49:58,100
But you didn't
believe me, did you?

994
00:49:58,100 --> 00:49:58,841
Good.

995
00:49:58,841 --> 00:50:01,090
OK, one of the things you're
going to have to memorize

996
00:50:01,090 --> 00:50:03,500
is the numbering system here.

997
00:50:03,500 --> 00:50:07,110
This is number one,
two, three, four, five,

998
00:50:07,110 --> 00:50:09,840
or to be totally
frank, and you know

999
00:50:09,840 --> 00:50:13,880
I'm always that, one prime, two
prime, three prime, four prime,

1000
00:50:13,880 --> 00:50:15,314
five prime.

1001
00:50:15,314 --> 00:50:16,980
And that numbering
system, it turns out,

1002
00:50:16,980 --> 00:50:21,080
is going to be very important
for our subsequent discussions.

1003
00:50:21,080 --> 00:50:24,150
Notice here that, for
example, it's here

1004
00:50:24,150 --> 00:50:27,720
at the two prime position that
this deoxyribose is lacking

1005
00:50:27,720 --> 00:50:34,720
the oxygen that is
present normally in RNA.

1006
00:50:34,720 --> 00:50:38,650
And, with all this in mind,
we will wait in great suspense

1007
00:50:38,650 --> 00:50:41,280
until Wednesday when
we actually talk

1008
00:50:41,280 --> 00:50:45,700
about how this is exploited to
make highly complex polymers.

1009
00:50:45,700 --> 00:50:46,740
Have a good two days.

1010
00:50:46,740 --> 00:50:48,740
See you Wednesday at 10:00.