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Whenever pathways are given with compartmental localization, it will usually be
important to know the impact of that localization.
Glucose (food carbohydrate, blood sugar)
phosphofructokinase
A little ATP
+
A little NADH
AMP
ATP
GP
shuttle
ADP
Pyruvate
If GP shuttle saturated:
Ox.
FADH2 NADH
Phos.
Pyruvate + NADH -> lactic acid.
acetyl CoA
citrate
OA
several
NADH
mitochondrion
Fatty acid synthesis
NADH
ADP
+
Isocitrate dehydrogenase
http://biochem.uthscsa.edu/hardies-bin/survey.pl
a) Coordination of glycolysis with fatty acid synthesis is relevant in all tissues.
b) Coordination of glycolysis with fatty acid synthesis is relevant in liver, but
not in muscle.
c) All kinds of tissues tend to produce lactic acid if overworked.
d) Liver won’t produce lactic acid. It will take up lactic acid and reconvert it to
glucose.
Note that the emphasis is on key molecules that connect or
interregulate pathways, and on regulatory enzymes.
So far, we’ve discussed cell autonomous regulation of glycolysis.
Cells also regulate their energy pathways according to overall glucose
availability.
High blood glucose leads to secretion of the hormone insulin.
Low blood glucose leads to secretion of the hormone glucagon.
Liver cells have a responsibility to support blood glucose levels by first
releasing glucose from their internal glycogen stores, and if necessary
synthesizing glucose from amino acids. They will shut down glycolysis
and rely on other energy sources for their own needs under these
conditions.
Liver cells also have a responsibility to convert excess glucose to fatty
acids. Under conditions of high blood glucose, they will override the
ATP inhibition to allow allow glucose to be converted to citrate, and
hence to fatty acids.
PFK-2 Regulates Levels of F-2,6bisP
Lack of F-2,6bisP essentially
shuts down
glycolysis in
liver, so as not to
form a futile
cycle with
gluconeogenesis
(overrides ATP inhibition)
Influence of blood sugar on glycolysis in liver.
High blood sugar;
Insulin
Low blood
sugar;
glucagon
Glucose (food carbohydrate, blood sugar)
phosphofructokinase
A little ATP
+
A little NADH
AMP
ATP
GP
shuttle
ADP
Pyruvate
If GP shuttle saturated:
Ox.
FADH2 NADH
Phos.
Pyruvate + NADH -> lactic acid.
acetyl CoA
citrate
OA
several
NADH
mitochondrion
Fatty acid synthesis
NADH
ADP
+
Isocitrate dehydrogenase
In gluconeogenic tissues (liver, kidney, intestines), glycolysis has to be
reciprocally regulated with gluconeogenesis to avoid futile cycling.
Most of the enzymes in gluconeogenesis and glycolysis are the same. Key
irreversible steps are bypassed by a different enzyme in gluconeogenesis.
gluconeogenesis
glycolysis
F-6-P
fructose
bisphosphatase
ATP
phosphofructokinase
F-1,6-P
ADP
F-2,6-P, AMP,insulin –
F-2,6-P, AMP, insulin +
ATP, citrate, glucagon +
ATP, citrate, glucagon -
The role of different resources in consolidating you knowledge:
Wikipedia is a great resource to rapidly update or remind yourself of some basic
information.
However, Wikipedia, class notes from other universities on the web, and the
primary literature can lead you into substantial complications that your instructor
chose to ignore. For example, there are five different versions of PFK2 with
different sensitivities to insulin and glucagon regulation, and expressed in
differrent tissues. The instructor in this course chose to only talk about reciprocal
regulation of glycolysis and gluconeogenesis in the liver.
Lecture slides reveal what the instructor chose to discuss and indicate a level of
detail. He probably went into greater detail than he expected you to be able to
reproduce on the exam. Looking at past exams will help clarify his expectations
of you.
If you missed a point in lecture, you will probably not be able to figure out what it
was by looking at the lecture slides. The lecture slides generally have just
pictures and not sentences. The course manual will usually cover the same
material, but with sentences. The course manual is not up to date with the
lectures in all cases.
Summary:
For each pathway:
What is if for and how is it regulated is of the highest priority.
Names of regulatory enzymes and molecules that regulate or coordinate the
pathway with other pathways are of the highest priority to know by name.
Subcellular localization and movement of molecules between compartments to
support the pathway is usually of relevance to know.
If the pathway is described as localized to a tissue, that would be important to
know. It should make sense with respect to your understanding of the role of
that tissue in support of global metabolism.
If hormonal regulation is specified, that is always important to know. It should
make sense with respect to what physiological state the hormone signifies.
How is glycolysis regulated?
a)
b)
c)
d)
e)
Which one of the following statements about glycolysis if FALSE?
a)
b)
c)
d)
e)