biochem lecture 15 review
What is the mechanism of glycogen cleavage by a phosphorylase and what is the product of this reaction? What must happen to the reaction product before it can feed into glycolysis?
Phosphorylase a attacks the non-reducing end of the glycogen molecule, releasing the alpha-1,4 linked glucose units as glucose-1-phosphate. The transferase enzyme and alpha-1,6 glycosidic enzyme covert the alpha-1,6 branches into linear alpha-1,4 glucose units. Glucose-1-phosphate is converted to glucose-6-phosphate by the enzyme phosphoglucomutase. Glucose-6-phosphate then enters the glycolysis pathway.
What does it mean that glycogen breakdown proceeds from the non-reducing end of the molecule? Why are at least three enzymes needed for glycogen breakdown?
Phosphorylase a attacks the non-reducing end of the glycogen molecule, releasing the alpha-1,4 linked glucose units as glucose-1-phosphate. This phosphorylase a enzyme cannot attack the glucose units near the alpha-1,6 branch points. Instead, additional enzymes are required, the transferase enzyme and alpha-1,6 glycosidic enzyme convert the alpha-1,6 branches into linear alpha-1,4 glucose units.
What is a protein kinase, and how do such kinases phosphorylate other proteins? Which R-groups are subject to phosphorylation by protein kinases? How can phosphorylation activate glycogen phosphorylase and inactivate glycogen synthase?
Protein kinases are enzymes that modify proteins by phosphorylating them.
What is the pentose pathway? What is the initial substrate for the pathway? Of what significance are the two major metabolic products of the pathway—NADPH and ribulose-5-P/ribose-5-P? How are NADPH and ribose-5-P used in human metabolism?
The pentose pathway is an alternate pathway to glycolysis that produces NADPH, which is the reducing power for anabolic biosynthetic pathways. This pathway generates pentose sugars and some of its reactions are integrated with glycolysis and gluconeogenesis. All of its reactions take place in the cytosol of the cell. NADPH is the reducing power utilized in anabolic reactions. When ribulose-5-phosphate is produced, further reactions are needed to convert excess ribulose-5-phosphate into usable intermediates, such as G3P and fructose-6-phosphate.
What is the chemical structure of cyclic-AMP? What does it mean that cyclic-AMP is a second messenger and how does it carry out that function? How is cyclic-AMP inactivated?
Adenylate cyclase converts ATP to cAMP. Second messengers are intracellular signaling molecules that are synthesized or degraded in response to the action of an extracellular hormone. The conversion of ATP to cAMP is essentially irreversible because it involves the breakdown of pyrophosphate, which is typically a very favorable reaction.
What would happen if glycogen synthesis and breakdown were to occur simultaneously? How does hormonal regulation by the epinephrine cascade prevent both of these processes from working simultaneously? What is the other name for epinephrine? How is epinephrine synthesized from tyrosine?
Adrenaline/ epinephrine is derived from the amino acid tyrosine. It stimulates a series of reactions that result in the activation of phosphorylase a, which degrades glycogen, and stimulates a series of reactions that inhibit glycogen synthase. The epinephrine cascade involves: - the binding of the hormone to activate an extracellular receptor protein - the activation of a G protein by interaction with an activated extracellular receptor - the activation of adenylate cyclase by interaction with a G protein - the conversion of ATP to cAMP by adenylate cyclase - the activation of protein kinase A by cAMP - the activation of phosphorylase kinase by a phosphorylase reaction catalyzed by a cAMP-sensitive kinase - the conversion of phosphorylase B to phosphorylase A by phosphorylase kinase - the cleavage of glycogen by phosphorylase a The dual activity of this cascade in activating glycogen hydrolysis and inhibiting glycogen synthesis prevents the occurrence of a futile cycle, during which energy would be wasted.
What two linkages join the glucose units of glycogen together? What do the numbers and alpha designator in these linkages signify? What is the net effect of branching in glycogen on the kinetics of glycogen breakdown?
Alpha-1,4 linkages and alpha-1,6 linkages join glucose units together. The alpha signifies that the oxygen within the linkage is located below the rings, and the numbers signify which carbons the bond is linked at. The many branches provide non-reducing ends where hydrogens cannot attach. These ends are subject to enzymatic hydrolysis. The net effect is that there is only one reducing end where glycogen can undergo mutarotation.
When glycogen is synthesized from glucose-6-P what three enzymes are involved? How does the formation of UDP-glucose energize glycogen synthesis? Why must glycogen synthesis involve different enzymes than glycogen breakdown?
Glucose-6-phosphate is converted back to glucose-1-phosphate. Glucose-1-phosphate reacts with UTP to form UDP glucose and release an inorganic pyrophosphate by the enzyme UDP-glucose-pyrophosphorylase. Glycogen synthase is then used to transfer the glucose unit from UDP glucose to the non-reducing end of glycogen. UDP is released as a result. The three enzymes involved are phosphoglucomutase, UDP-glucose-pyrophosphorylase, and glycogen synthase. The inorganic pyrophosphate released during the conversion of glucose-1-phosphate to UDP-glucose can be hydrolyzed to form two inorganic phosphates. This energy-releasing reaction helps drive the pathway toward product formation. Glycogen hydrolysis and synthesis involve different enzymes, which allows both processes to be energy releasing and to be subject to hormonal regulation so that both systems don't function simultaneously (which would result in a futile enzyme cycle that would waste energy and yield no net product).
How does the amount of energy stored in glycogen compare to the amount stored as triacylglycerols? What two reasons make glycogen a less efficient energy storage material than triacylglycerols? Why is glycogen such a critical factor in human survival?
Triglycerols store more caloric energy per gram (9kcal/g) than glycogen does (4kcal/g). Lipids are more energy dense than carbohydrates are. However, glycogen is a critical factor in human survival because the brain uses only glycogen except during starvation because it is a readily available source of energy in the body.
What type of reaction is catalyzed by the two enzymes that produce NADPH? If the pentose pathway did not exist, what alternate types of reactions might be used to produce NADPH?
Two oxidation reactions catalyze the two enzymes that produce NADPH. The conversion of glucose-6-phosphate to 6-phosphogluconolacetone by the enzyme glucose-6-phosphate dehydrogenase produces NADPH. The conversion of 6-phosphogluconate to ribulose-5-phosphate by the enzyme 6-phosphogluconate dehydrogenase also produces NADPH.