Biochem - Quiz 9

glycogen

a highly branched homopolymer of glucose, found in all tissues

where are most glycogen stores found?

liver and muscle

function of liver in terms of glycogen?

breaks down glycogen and releases glucose to the blood to provide energy for the brain and RBCs

two types of linkages in glycogen

alpha-1,4 and alpha-1,6

non-reducing end

the end from which glucose units are removed during degradation of glycogen.

how often do alpha-1,6 linkages occur?

every 12 glucose molecules (branch point)

what are the four enzymes involved in glycogen breakdown?

glycogen phosphorylase, phosphoglucomutase, transferase, a-1,6-glucosidase

glycogen phosphorylase

enzyme that cleaves glucose from the non-reducing end of a glycogen branch by adding a phosphate. catalyzes a phosphorolysis reaction that yields glucose 1-phosphate

phosphoglucomutase

converts glucose-1-phosphate to glucose-6-phosphate

what can glycogen phosphorylase cleave?

only a-1,4 glycosidic bonds, cannot cleave at branch points!

transferase

shifts a small oligosaccharide near the branch point to a nearby chain, making the glucose moieties accessible to phosphorylase

a-1,6-glucosidase

de-branching enzyme, cleaves the a-1,6 bond at the branch point, releasing a free glucose

a-1,6-glucosidase catalyzes what type of reaction?

hydration reaction

phosphoglucomutase rxn has what intermediate?

glucose 1,6-bisphosphate

glucose 6-phosphatase

generates free glucose from glucose 6-phosphate in liver

where is glucose 6-phosphatase found?

membrane of the ER, lumen side. found only in liver

liver phosphorylase

produces glucose for use by other tissues

key regulatory enzyme for glycogen degradation?

glycogen phosphorylase

what forms does phosphorylase exist in?

less active b form and more active a form

what is different in a form than b form?

serine residue 14 is phosphorylated in a form

what state is favored in the b form?

T state

what state is favored in the a form?

R state

in the T state, what do the alpha helices do?

block the active site, preference for R form

key role of the liver?

maintain adequate blood glucose levels

default state of liver phosphorylase?

a form in the R state

what is a negative regulator of liver phosphorylase?

glucose (facilitates transition from R to T state)

liver phosphorylase and muscle phosphorylase are

isozymes

default state of muscle phosphorylase

b form in the T state

when energy is needed in the muscle, AMP rises and

the phosphorylase binds AMP, stabilizes the R state

The T state of the phosphorylase is stabilized by

ATP and glucose 6-phosphate

type I muscle fibers

slow twitch fibers, rely primarily on cellular respiration as a means of generating ATP

type IIb muscle fibers

fast twitch fibers, rely primarily on lactic acid fermentation for ATP generation

type IIa muscle fibers

biochemical characteristics intermediate to the other fiber types

which fibers are rich in glycogen phosphorylase?

type IIb (more need for glucose)

metabolic type: type I

oxidative

metabolic type: type IIa

oxidative/glycolytic

metabolic type: type IIb

glycolytic

phosphorylation is stimulated by what hormones?

glucagon and epinephrine

phosphorylase kinase

the enzyme responsible for the conversion of glycogen
phosphorylation from the unphosphorylated b state to the a state

what is phosphorylase kinase activated by?

phosphorylation and calcium ions

what is phosphorylase kinase phosphorylated by?

protein kinase A

calmodulin

the delta subunit of phosphorylase (calcium sensor)

when is phosphorylase kinase maximally active?

when phosphorylated and bound to calcium

what signals the need for glycogen breakdown?

epinephrine and glucagon

what transmits the signal for the initiation of glycogen breakdown?

G proteins

what do glucagon (liver) and epinephrine (muscle) do?

initiate G-protein cascade, result in cAMP production

In liver, Ca2+ release is stimulated by

epinephrine binding to the a-adrenergic receptor, activates the G-protein, instigates phosphoinositide cascade

glycogen breakdown must be?

rapidly turned off when necessary

what renders G proteins inactive?

inherent GTPase activity

phosphodiesterase

converts cAMP to AMP (does not stimulate protein kinase A)

protein phosphatase 1

removes phosphorylase groups from phosphorylase kinase and glycogen phosphorylase (inactivates the enzymes)

glycogen synthesis

when there is lots of glucose (fed state)

UDP-glucose

activated form of glucose. monomer that is used to extend the glycogen chain in synthesis

what is UDP-glucose synthesized from?

glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase

UDP-glucose pyrophosphorylase reaction is irreversible by the?

hydrolysis of pyrophosphate

key regulatory enzyme in glycogen synthesis

glycogen synthase

glycogen synthase

transfers a glucose moiety from UDP-glucose to the C-4 terminal residue of a glycogen chain to form an a-1,4-glycosidic bond

what does glycogen synthase require?

an oligosaccharide of glucose residues as primer

glycogenin

core protein of glycogen, synthesizes the primer (dimer of two identical subunits)

each subunit of glycogenin generates

an oligosaccharide of glucose residues 10-20 glucosyl units long

glycogen synthase can only synthesize what linkages?

a-1,4 linkages

what does the branching enzyme do?

generates branches by cleaving an a-1,4 linkages and taking a block of approximately seven glucoses and synthesizing an a-1,6 linkage

glycogen synthase inactive in the

phosphorylated b form

glycogen synthase active in the

unphosphorylated a form

key regulatory process for glycogen synthase is?

conversion of b form in T state to R state of b form by binding of glucose 6-phosphate

how many molecules of ATP are required to incorporate dietary glucose into glycogen?

2

the complete oxidation of glucose derived from glycogen yields how many ATP?

31

how is glycogen synthesis inhibited?

by the same glucagon and epi signaling pathways that stimulate glycogen breakdown

phosphorylation of glycogen synthase by protein kinase A to form glycogen synthase b _______

inhibits glycogen synthesis

glycogen synthase kinase

phosphorylates and inhibits glycogen synthase

PP1

enzyme that activates glycogen synthase (removes phosphorylase groups from b, makes it a)

what does PP1 consist of?

a catalytic subunit and of a family of regulatory subunits

key regulatory subunit of PP1

G subunit

G subunit

binds glycogen and the catalytic subunit of PP1, localizing the enzyme with its substrates

how does insulin stimulate glycogen synthesis?

by inactivating glycogen synthase kinase, also increases the number of glucose transporters (GLUT4) in PM

NADPH

key product of pentose phosphate pathway, source of biosynthetic reducing power

what are ribose sugars used for?

replication of DNA and transcription

pentose phosphate pathway

a metabolic process that produces NADPH and ribose 5-phosphate for nucleotide synthesis

first phase of PPP

oxidative generation of NADPH

second phase of PPP

nonoxidative interconversion of a variety of sugars

glucose 6-phosphate dehydrogenase

the rate-limiting enzyme in the pentose phosphate pathway. converts glucose 6-phosphate into 6-phosphoglucono-delta-lactone, coverts NADP+ to NADPH

lactonase

converts 6-phosphoglucono-delta-lactone to 6-phosphogluconate

6-phosphogluconate dehydrogenase

converts 6-phosphogluconate to ribulose-5-phosphate

what is the product of the oxidative phase of PPP?

ribulose-5-phosphate

phosphopentose isomerase

ribulose-5-phosphate to ribose-5-phosphate

how is PPP linked to glycolysis?

by transketolase and transaldolase

how many carbons does transketolase move?

2 carbons

how many carbons does transaldolase move?

3 carbons

first reaction of non-oxidative pathway?

C5 and C5 acted upon by transketolase to make C3 and C7

second reaction of non-oxidative pathway?

C3 and C7 acted upon by transaldolase to make C6 and C4

third reaction of non-oxidative pathway?

C4 and C5 acted upon by transketolase to make C6 and C3

net result of non oxidative phase reactions

3 C5 --> 2 C6 + C3 (three pentoses into two hexoses and one triose)

what are the first two C5 molecules known as?

xylulose 5-phosphate and ribose 5-phosphate

phosphopentose epimerase

ribulose-5-phosphate to xylulose-5-phosphate

two fates of ribulose-5-phosphate

become ribose 5-phosphate or xylulose 5-phosphate

what is GAP?

glycolytic intermediate, fed into glycolysis

the rate of the oxidative phase in PPP is controlled by the concentration of?

NADP+

how many modes can the PPP operate in?

4

glutathione

reducing agent that can help reverse radical formation before damage is done to the cell

what is required to maintain adequate levels of reduced glutathione?

NADPH generated by PPP