Chapter 25 Flashcards
Glycogen synthesis requires _______
a) UDP-glucose
b) UTP-glucose
c) Phosphoenolypyruvate
d) Glyceraldehyde-3-phosphate
a) UDP-glucose
UDP-glucose is the activated form of _______, and acts as the substrate for enzyme ______
a) glucose; enolase
b) glucose; glycogen synthase
c) glycogen; protein kinase A
d) glycogen; glycogen synthase
b) glucose; glycogen synthase
A common enzyme in glycogen synthesis and degradation is ________
a) hexokinase
b) triosephosphate isomerase
c) phosphoglucomutase
d) phosphoglycerate kinase
c) phosphoglucomutase
UDP-glucose is synthesized by ____________, with the substrates (reactants) being ________ and ________, and the products being _________ and _________
UDP-glucose pyrophosphorlyase; UTP and glucose 1-phosphate; UDP-glucose and pyrophosphate
Glycogen Synthase & Glycogenin
Glycogen synthase = key regulatory enzyme in glycogen synthesis
- It transfers a glucose moiety from UDP-glucose to the C4 terminal residue of a glycogen chain to form an alpha 1,4-glycosidic bond
Glycogen synthase requires an oligosaccharide of glucose residues as the primer: glycogenin (glucose oligosaccharide)
- Glycogenin = dimer of 2-identical subunits
- Each subunit generates an oligosaccharide, w/ alpha 1,4-glycosidic bonds, of 10-20 glucose residues long ~ glycogen synthase then extends this primer
Glycogenin remains attached to glycogen via a tyrosine residue
Explain how the branching enzyme works
- Branching enzyme is required to form alpha 1-6 glycosidic bonds since glycogen synthase can only form alpha-1,4-glycosidic bonds
- Branching enzyme generates branches by cleaving an alpha-1,4-glycosidic bond and transferring a block of approx. 7-glucose residues, and synthesizing an alpha-1,6-linkage
- The chain that was broken must have at least 11 glucose residues
- The branch will form via new α-1,6-linkage that’s 4 residues inward from end of chain
- Glycogen synthase enzyme can then continue to extend a branched polymer
Glycogen synthase is usually ______ when in phosphorylated B form (T-state) and usually ______ when in unphosphorylated A form (R-State)
a) inactive; active
b) active; inactive
a) inactive; active
_____ molecules of ATP are required to incorporate dietary glucose into glycogen
a) 3
b) 4
c) 2
d) 2.5
c) 2
Complete oxidation of glucose derived from glycogen generates a ____ amount of ATP
a) high
b) low
a) high (31 ATP)
Explain how glycogen breakdown and synthesis are reciprocally regulated
Glycogen synthase (glycogen synthesis) is inhibited by the same glucagon (fasting) and epinephrine (exercise) signaling pathways that stimulate glycogen breakdown
Phosphorylation of glycogen synthase by PKA to form glycogen synthase B inhibits glycogen synthesis
Glycogen synthase kinase also phosphorylates and inhibits glycogen synthase
Explain the process of turning on Glycogen Synthesis
Removal of glucagon/epinephrine signal =
- Inactivation of PKA
- Activation of protein phosphatase 1 (PP1)
Protein phosphatase 1 (PP1) reverses the regulatory effects on glycogen synthase
- PP1 shifts glycogen metabolism from degradation mode to synthesis mode
- PP1 stimulates glycogen synthesis by removing the phosphoryl groups from glycogen synthase B and converting it into the more active A form (glycogen synthase A)
- PP1 also removes phosphoryl groups from phosphorylase kinase and phosphorylase A, thus inhibiting (stopping) glycogen degradation
Regulation of Protein Phosphatase 1: Epinephrine/Glucagon
Protein phosphatase 1 (PP1) consists of a catalytic subunit and a family of regulatory subunits
A key regulatory subunit is G subunit: GL in the liver or GM in the muscle
- In muscle, phosphorylation of GM results in the release of the catalytic subunit of PP1 and a decrease in the enzymes activity
Almost all tissues contain small proteins that when phosphorylated inhibit the catalytic subunit of PP1
Regulation of Protein Phosphatase 1: Insulin
- Insulin results in phosphorylation and inactivation of glycogen synthase kinase
- PP-1 can then dephosphorylate glycogen synthase generating the active a form
- Insulin also causes translocation of glucose transporters (GLUT4) to cell surface to increase glucose uptake
- Glucose is phosphorylated to glucose 6-phosphate, which can activate glycogen synthase even in the b form
Glucose metabolism in liver regulates blood glucose concentration: steps
- Glycogen degradation in liver is inhibited (stopped) and glycogen synthesis is stimulated by high blood glucose levels
- Conversion of glycogen phosphorylase A from R-state to T-state by binding of glucose = activation of PP1, which is associated w/ phosphorylase
- PP1 converts glycogen metabolism from a degradation mode to a synthesis mode
- The lag between the decrease in degradation and increase in synthesis is accounted for by fact that initially there’s about 10-phosphorylase A molecules per molecule of phosphatase, thus most of phosphorylase A is converted into B before any phosphatase is released
