QUIZ 9

quiz nine flashcards mcb 2000

Glycogen

A highly branched homopolymer of glucose present in all tissues.

The largest stores of glycogen are in the?

Liver and muscle

The liver breaks down _____ and releases _____ to the blood to provide energy for the _____ and the ___ _____ _____.

1) glycogen
2)Glucose
3) brain
4) red blood cells

Muscle glycogen stores are mobilized to provide?

Energy for muscle contraction.

what is the Glycogen structure?

the residues at the nonreducing ends are shown in red and the residue that starts a branch is shown in green. The rest of the glycogen molecule is represented by R.

List and describe the steps of glycogen breakdown and identify the enzymes required.

1.Glycogen phosphorylase
2.Phosphoglucomutase.
3.Transferase
4.α-1,6-glucosidase

Glycogen phosphorylase degrades glycogen from the

nonreducing ends of the glycogen molecule

The phosphorylase catalyzes a

phosphorolysis reaction that yields glucose 1-phosphate.

Glucose 1-phosphate is converted into glucose 6-phosphate by

phosphoglucomutase

A Debranching Enzyme Also Is Needed for?

the Breakdown of Glycogen

Glycogen phosphorylase cannot cleave near branch points

can only cleave α-1,4-glycosidic bonds.thereby making the glucose moieties accessible to the phosphorylase

A debranching enzyme (α-1,6-glucosidase) then cleaves the α-1,6 bond at the branch point, releasing

a free glucose.

Phosphoglucomutase forms

glucose 6-phosphate from glucose 1-phosphate with the use of a glucose 1,6-bisphosphate intermediate

Glucose 6-phosphatase generates

•free glucose from glucose 6-phosphate in liver.

where is Glucose 6-phosphatase

-Found in membrane of the ER, lumen side

The free glucose is released into the blood for use by other tissues such as

the brain and red blood cells.

_____________ is absent in most other tissues

Glucose 6-phosphatase

What enzymes are required for the liver to release glucose into the blood when an organism is asleep and fasting?

Phosphorylase, transferase, glucosidase, phosphoglucomutase, and glucose 6-phosphatase

The Phosphorylase Dimer

Phosphorylase a is phosphorylated on serine 14 of each subunit. This modification favors the structure of the more active R state. One subunit is shown in white, with helices and loops important for regulation shown in blue and red. The other subunit is shown in yellow, with the regulatory structures shown in orange and green. Phosphorylase b is not phosphorylated and exists predominantly in the T state. Notice that the catalytic sites are partly occluded in the T state. [Drawn from 1GPA.pdb and 1NOJ.pdb.]

Phosphorylase Is Regulated by

Allosteric Interactions and Reversible Phosphorylation

Liver Phosphorylase Produces

Glucose for Use by Other Tissues

The key regulatory enzyme for glycogen degradation is

glycogen phosphorylase

Phosphorylase exists in two forms

•a less active b form and a more active a form.

The a form differs from the b form in that

a serine residue is phosphorylated.

Both the a form and b form display _____

RóT equilibrium

In the b form the ________ is favored whereas in the a form, the _______ is favored

1) T state
2) R-state

Phosphorylase Regulation

Both phosphorylase b and phosphorylase a exist in equilibrium between an active R state and a less active T state. Phosphorylase b is usually inactive because the equilibrium favors the T state. Phosphorylase a is usually active because the equilibrium favors the R state. In the T state, the active site is partly blocked by a regulatory structure. The active site is unobstructed in the R state. Regulatory structures are shown in blue and green.

Liver Phosphorylase Produces

Glucose for Use by Other Tissues

A key role of the liver is to?

maintain adequate blood levels of glucose.

As a result, the default state of liver phosphorylase is the

a form in the R state.

In essence, liver phosphorylase is prepared to generate?

blood glucose unless signaled otherwise

Glucose is a negative regulator of

liver phosphorylase

Glucose facilitates the transitionfrom ______

the R state to the T state

______ _____ and ______ ______ are isozymes

Liver phosphorylase and muscle phosphorylase

Allosteric Regulation of Muscle Phosphorylase

Binding of glucose to phosphorylase a shifts equilibrium to T state, inactivating the enzyme. Glycogen is not mobilized when glucose is already abundant.

Muscle Phosphorylase Is Regulated by

the Intracellular Energy Charge

In muscle, the default form of the phosphorylase is the

b form in the T state.

When energy is needed, as signaled by an increase in the concentration of AMP, the phosphorylase binds?

AMP, which stabilizes the R state.

The T state of the phosphorylase is stabilized by __ and ___

ATP and glucose 6-phosphate.

phosphorylase b is predominate, and is inactive in

muscle cells

Allosteric Regulation of Liver Phosphorylase

The binding of glucose to phosphorylase a shifts the equilibrium to the T state and inactivates the enzyme. Thus, glycogen is not mobilized when glucose is already abundant. Regulatory structures are shown in blue and green.

Compare the allosteric regulation of phosphorylase in the liver and in muscle and explain the significance of the difference.

In muscle, the b form of phosphorylase is activated by AMP. In the liver, the aform is inhibited by glucose. The difference corresponds to the difference in the metabolic role of glycogen in each tissue. Muscle uses glycogen as a fuel for contraction, whereas the liver uses glycogen to maintain proper blood glucose concentration

Muscle is composed of several fiber types

-Type I, or slow-twitch fibers, rely primarily on cellular respiration as a means of generating ATP.
-Type IIb (type IIx), or fast-twitch fibers, rely primarily on lactic acid fermentation for ATP generation.
-Type IIa fibers have biochemical characteristics intermediate between the other fiber types

Type IIb fibers are rich in

glycogen phosphorylase

Phosphorylase exists in two forms

a less active b form and a more active a form

The a form differs from the b form in that a ______

a serine residue 14 is phosphorylated.

Phosphorylation is stimulated by the hormones

glucagon and epinephrine (adrenaline).

Phosphorylation alters the active site such that

α helices that partially block the active site in the b form are removed.

phosphorylase kinase

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

Phosphorylase kinase itself is activated by both

phosphorylation and Ca2+ binding

Phosphorylase kinase is phosphorylated by

protein kinase A

calmodulin

The δ (delta) subunit of phosphorylase

Phosphorylase kinase is maximally active when

phosphorylated and bound to calcium

G Proteins Transmit the Signal for

the Initiation of Glycogen Breakdown

Glucagon (in liver) and epinephrine (in muscle) initiate

G-protein cascades that result in the production of cAMP.

Calcium, released in muscle to stimulate contraction, initiates

the activation of phosphorylase kinase.

In liver, Ca2+ release is stimulated by

•epinephrine binding to the α-adrenergic receptor, which activates a G-protein, instigating the phosphoinositidecascade.

Cyclic AMP activates

protein kinase A

Phosphorylase kinase converts

glycogen phosphorylase b to the a form, activating glycogen degradation.

Hormonal Control of Glycogen Breakdown

The left side of the illustration shows the hormonal response to fasting. Glucagon stimulates glycogen breakdown in the liver when blood glucose is low. The right side of the illustration shows the hormonal response to exercise. Epinephrine enhances glycogen breakdown in muscle and the liver to provide fuel for muscle contraction.

regulatory cascade for glycogen breakdown

Glycogen degradation is stimulated by hormone binding to 7TM receptors. Hormone binding initiates a G-protein-dependent signal-transduction pathway that results in the phosphorylation and activation of glycogen phosphorylase.

Glycogen degradation is turned off by

several mechanisms

The inherent GTPase activity of the G protein renders

proteins inactive

Phosphodiesterase converts

cAMP into AMP, which does not stimulate protein kinase A.

Protein phosphatase 1 removes

phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, thereby inactivating the enzymes.

The onset of fatigue coincides with __________________

the depletion of glycogen reserves.

Depletion as a Result of Exercise

A) Glycogen content of the vastus lateralis decreases as a function of time at 80% effort. (B) The French cyclist Tony Gallopin slumps in exhaustion after winning a stage in the 2014 edition of the Tour de France. [(A) After J. Bergströmand E. Hultman, A study of the glycogen metabolism during exercise in man

25.1 Glycogen Is ___ and _____by Different Pathways

Synthesized
Degraded

Glycogen degradation yields

glucose 1-phosphate.

UDP-glucose is the _____that is used to____ the ___

monomer
extend
glycogen chain in synthesis.

UDP-glucose is an

activated form of glucose.

what is the glucose donor in glycogen synthesis?

Uridine diphosphate glucose (UDP-glucose)

UDP-glucose is synthesized by

UDP-glucose pyrophosphorylase.

UDP-glucose pyrophosphorylase reaction is _____under cellular conditions

irreversible

The reaction is subsequently rendered irreversible by the

hydrolysis of pyrophosphate

Glycogen synthase

the key regulatory enzyme in glycogen synthesis

Glycogen synthase transfers a glucose moiety from

UDP-glucose to the C-4 terminal residue of a glycogen chain

what does the transfer of a glucose moiety to the c-4 terminal residue form?

α-1,4-glycosidic bond

Glycogen synthase requires an

oligosaccharide of glucose residues as a primer.

glycogenin

synthesizes a primer and is a dimer of two identical subunits

Each subunit of glycogenin generates an

oligosaccharide of glucose residues 10–20 glucosyl units long.

Glycogen synthase then ____ this primer

extends

Glycogen synthase can only synthesize

α-1,4-linkages.

A branching enzyme generates branches by

cleaving an α-1,4-linkage and taking a block of approximately seven glucoses and synthesizing an α-1,6-linkage.

Glycogen synthase can then extend the

branched polymer.

Glycogen synthase is usually inactive when in the

phosphorylated b form

Glycogen synthase isis usually active when in the

unphosphorylated a form

key regulatory process for glycogen synthase

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

phosphorylation has ______ effects on glycogen synthase than on glycogen phosphorylase

oposite

Why is the fact that phosphorylation has opposite effects on glycogen synthesis and breakdown advantageous?

Prevents both processes from occurring simultaneously. Prevents wasteful energy expenditure.

Glycogen Is an Efficient Storage Form of

Glucose

Only ____ molecules of ATP are required to incorporate dietary glucose into glycogen

two

The complete oxidation of glucose derived from glycogen yields

31 molecules of ATP.

Coordinate Control of Glycogen Metabolism

Glycogen metabolism is regulated, in part, by hormone-triggered cyclic AMP cascades. The sequence of reactions leading to the activation of protein kinase A ultimately activates glycogen degradation. At the same time, protein kinase A, along with glycogen synthase kinase, inactivates glycogen synthase, shutting down glycogen synthesis.

Protein phosphatase 1 (PP1) shifts glycogen metabolism from

the degradation mode to the synthesis mode

PP1 removes phosphoryl groups from glycogen synthase b, converting it into

the more active a form

PP1 also removes phosphoryl groups from

phosphorylase kinase and phosphorylase a, inhibiting glycogen degradation.

Regulation of Glycogen Synthesis by Protein Phosphatase 1

PP1 stimulates glycogen synthesis while inhibiting glycogen breakdown.

Protein phosphatase 1 consists of

a catalytic subunit (PP1) and one of a family of regulatory subunits

A key regulatory subunit is

the G subunit (GL in liver and GM in muscle) that binds glycogen and the catalytic subunit of PP1, localizing the enzyme with its substrates