Anabolic Metabolism: Glycogenolysis, Glycogenesis, and Gluconeogenesis

Question 1

Outline how monosaccharides are generated from polysaccharide glycogen

Answer 1

multiple enzymes are necessary
Glycogen Phosphorylase - uses phosphate to remove and phosphorylate the terminal glucose monomer to glucose-1-P

alpha1,4-1,4 glucotransferase - removes 3 monomers from the brand and reattaches on main branch

alpha 1,6 glucosidase - cleaves the alpha 1,6 clycosidic bond to produce glucose-1-P

Question 2

Describe how the activity of glycogen synthase, and glycogen phosphorylase is controlled by glucose/glucose-6-P, AMP/ATP, and hormones (glucagon, epinephrine, and insulin) in a fed versus a fasted state.

Answer 2

Glycogen synthase and Glycogen phosphorylase have opposing actions

Regulation from allosteric and covalent modification

COVALENT
Insulin: lowers blood [glucose] - activates Glycogen synthase

Glucagon/Epinephrine - increase blood [glucose] - activate glycogen phosphorylase

ALLOSTERIC
Glycogen phosphorylase: activated by high AMP, low G-6-P

Glycogen Synthase: activated by high ATP, high G-6-P

Question 3

Outline the transport and enzymatic preparation of glucose to form UDP-glucose, the substrate for glycogen synthase.

Answer 3

Glucose -(hexokinase) G-6-P - (phosphoglucomutase)G-1-P - (UPD-glucose pyrophosphorylase) “activated UDP-glucose molecules - (Glycogen synthase) Glycogen

Amylo-(1,4-1,6)-tranglycoxylase - removes a chain of 11 or more glucose and creates a branch

Question 4

Compare the utilization of different monosaccharides for the synthesis of glycogen

Answer 4

Galactose - Galactose1P - Glucose 1-P
Mannose - Mannose6 - F6P - G6P
Fructose - F6P

Question 5

Distinguish b/w metabolites that can be sources for gluconeogenesis and those than cannot

Answer 5

Alanine + Lactate are able to be used in gluconeogenesis because they can be converted to pyruvate

Fatty Acids cant because they are turned into Acetyle CoA

Question 6

Describe how the role of pyruvate carboxylase differs in myocytes than in hepatocytes in response to [Acetyl CoA] during fasting.

Answer 6

Muscle - aerobic: pyruvate carboxylase produces alot of OAA from pyruvate that can react with acetyl CoA in B-oxidaation

Liver - fasting: producse OAA from pyruvate so that gluconeogenesis can make glucose for the muscle
fed: produces OAA fomr pyruvate so that acetyl CoA can be shuttled out to the cytosol for fatty acid synthesis

Question 7

Describe how hepatic gluconeogenesis resolves circulating [lactate] & [alanine] while balancing cellular [NAD+]/[NADH + H+] ratios.

Answer 7

Large amounts of NADH is produce by glycolysis in the muscles = alot of [lactate] and [alanine] is produced

Large amounts of NADH is consumed by gluconeogenesis = resolved by producing pyruvate from lactate

both are linked by shipping lactate from muscles to liver

Question 8

Explain why the pyruvate kinase reaction cannot be reversed in gluconeogenesis like all the other glycolytic reactions

Answer 8

PEP to Pyruvate has a huge delta G (energy released in form of ATP formation) so the reverse reaction is highly unlikely