Biochemistry Lecture No. 16: Carbohydrate Metabolism
Tuesday October 16 , 2012
Overview Of Carbohydrate Metabolism:
-Carbohydrate metabolism encompasses 4 key bodily actions: Glycogen synthesis and breakdown,
glycolysis and fermentation, gluconeogenesis, and the pentose phosphate pathway.
Carbohydrate Storage As Glycogen:
-In the process of carbohydrate storage as glycogen, glycogen synthase catalyzes the conversion of
glucose-1-phosphate to glycogen using UTP (ATP equivalent) as an energy source, while glycogen
phosphorylase catalyzes the breakdown of glycogen to glucose-1-phosphate by way of phosphorylation
(P). As coupled UTP hydrolysis is required to convert glucose-1-phosphate into glycogen, it is unlikely
that glycogen synthase will convert glycogen into glucose-1-phosphate.
-An equilibrium between glucose-6-phosphate and glucose-1-phosphate is also established (they are
energetically neutral to each other). There is no equilibrium between glycogen and glucose-1-phosphate
because two different enzymes are utilized in catalysis.
Allosteric Regulation In Skeletal Muscle:
-In skeletal muscle cells, glucose-6-phosphate allosterically activates glycogen synthase, while AMP
activates glycogen phosphorylase. ATP and glucose-6-phosphate are both inhibitors of glycogen
Allosteric Regulation In Liver:
-The liver has isozymes, enabling it to respond to regulation in a slightly different manner than the
muscles do (neither ATP nor AMP regulate/inhibit glycogen phosphorylase activity in the liver). Glucose
is an allosteric inhibitor of glycogen phosphorylase (high blood sugar), while glucose-6-phosphate
allosterically activates glycogen synthase (same as in the muscles).
Control By Phosphorylation In Liver & Muscle:
-Insulin leads to the dephosphorylation of both enzymes in the liver and muscles (activates glycogen
synthase and deactivates glycogen phosphorylase). Glucagon leads to phosphorylation in the liver only
because the muscles are insensitive to glucagon, while the liver attempts to keep blood glucose levels
constant. Epinephrine leads to phosphorylation in the liver and muscles (activates glycogen
phosphorylase and deactivates glycogen synthase).
-Let it be noted also that the preferred energy source of the brain is glucose, which is why the liver
releases glucose to stimulate brain comprehension in times of stress (use of epinephrine). Net Reaction & ΔG Values For Glycolysis:
-The whole point of glycolysis is to make ATP and any monosaccharide can be incorporated and
converted in this pathway. The pyruvate from glycolysis would then be oxidized in the mitochondria, the
ATP is stored for useable energy, and the NADH head off to the electron transport chain in the
mitochondria. Steps 1, 3 and 10 (irreversible reactions) are targets for control of flux through glycolysis.
Control Of Flux Through Glycolysis:
-Citrate inhibits the pathway at step 3 by inactivating phosphofructokinase. Insulin also regulates
glycolysis among other things as high insulin level increases the amount of fructose-2, 6-bisphosphate,
which activates phosphofructokinase and allows the glycolysis pathway to proceed. High ATP
concentration is also recognized as inhibiting glycolysis at step 3, while high concentrations of AMP, ADP
or Piactivate glycolysis at step 3.
Strategies For Fermentation:
-Fermentation is a process that regenerates NAD (in order to convert glucose to pyruvate) and allows
ATP synthesis via gly