Transcript module 2
Glycolysis
Is it a good strategy to draw this out until you can produce it by memory?
NO
It is true that repeatedly testing recall is a way to assure that you have
successfully memorized a thing. Most students do that by internal
verbalization rather than actually drawing it out.
BUT
1) Unless the information is linked to other things, you won’t have any long
term memory of it.
2) Unless the specifics on that slide are linked to some learning objective that
you have, you’d be memorizing the wrong information.
The first thing you want to know about any metabolic pathway is:
What’s it for?
Glucose (food carbohydrate, blood sugar)
A little ATP
A little NADH
Pyruvate
If O2:
TCA cycle
Pyruvate -> CO2 + a lot of NADH
Ox. Phos.
NADH -> a lot of ATP.
If can’t use O2:
Pyruvate + NADH -> lactic acid.
Now you tell me a physiologic situation where the information
summarized on the previous slide is explanatory.
Go to http://biochem.uthscsa.edu/hardies-bin/survey.pl
When you’ve found something from the first presentation of today
that this slide explains, check “True” for (a) and click “submit”.
Then always know how the pathway is regulated, and be sure it
makes sense to you with respect to what the pathway is for.
Glucose (food carbohydrate, blood sugar)
inhibited if the cell has enough
ATP
phosphofructokinase
A little ATP
A little NADH
Pyruvate
If O2:
TCA cycle
Pyruvate -> CO2 + a lot of NADH
Ox. Phos.
NADH -> a lot of ATP.
If no O2:
Pyruvate + NADH -> lactic acid.
Since biochemists put a lot of emphasis on regulation, one should:
1) know the name of the regulated enzyme(s).
2) know the specifics of the regulation.
phosphofructokinase
stimulated by ADP, AMP
inhibited by ATP, citrate
At the moment we are considering the regulation of glycolysis in all cells
for the primary purpose of keeping up the ATP levels (also called the
“energy charge”).
Inhibition by ATP and/or stimulation by AMP and ADP obviously makes
sense with respect to that use of the pathway.
How about citrate?
If it’s not obvious, that would require looking up the role of citrate in
energy metabolism to consolidate your understanding of the control
of glycolysis.
Now you do some research using the internet of the course manual and tell me
which of the following statements about citrate might be reasonable
explanations about why it would inhibit phosphofructokinase.
a) Citrate is a high energy storage molecule, so excess ATP is converted to
citrate.
b) Citrate is an intermediate in breaking down pyruvate and sits before an
enzyme inhibited by high energy charge. So citrate builds up when ATP is
plentiful.
c) Since citrate can shuttle between the mitochondrion and the cytoplasm, it
can regulate glycolysis (in the cytoplasm) to keep pace with ATP production
(in the mitochondrion).
d) Under some circumstances glycolysis is driven not to make ATP but to
convert excess glucose to fat. Citrate is an intermediate between glycolysis
and fatty acid synthesis that can feed back to regulate glycolysis to match
the rate of fatty acid synthesis.
Go to http://biochem.uthscsa.edu/hardies-bin/survey.pl and give your opinion
as to whether each of the above statements is true or false.
Summary:
Every time you encounter how an enzyme is regulated, look through
all the other resources available to you to make sense of it.
Every time there is information about what subcellular compartment a
pathway occurs in, put that on your list of things to know.
A review of past test questions from the chapter on glycolysis reveals a
disportionate number of questions about the glycerol phosphate shuttle,
which is described in the course manual as so:
Why do you think that
the professor is so
interested in the
glycerol phosphate
shuttle?
a) This is the only way to make glycerol-3-P, which is needed for fatty acid
synthesis.
b) This is the only way to make FADH2, which is a necessary co-factor for some
enzymes.
c) This allows NADH made by glycolysis to be reconverted to NAD+, allowing
glycolysis to continue without having to divert the pyruvate to lactic acid. The
mitochondrial FADH2 is used to make more ATP.
d) At maximum muscular exertion, this pathway becomes limiting, glycolysis
makes a little excess ATP at the cost of having to make lactic acid, and the
lactic acid inhibits muscle function bringing the activity to an end.
Summary:
A review of past exam questions can reveal what issues are
considered important by a given professor, and what level of detail
that professor may expect of you.
He will not repeat the same questions from year to year, however. So,
simply memorizing the answers to last year’s exam will probably not
be helpful.