Chapter 16: Glycogen Metabolism and Gluconegenesis

Question 1

difference between glucose and glycogen

Answer 1

Glucose is a single sugar unit or monosaccharide. Glycogen is a multi-sugar unit or polysaccharide

Question 2

function of glycogen and starch?

Answer 2

Store glucose for metabolic use

Glycogen broken down so it can enter glycolysis

Question 3

In animals, a constant supply of glucose is essential for tissues such as?

Answer 3

the brain and red blood cells which depend almost entirely on glucose as an energy source

Question 4

The mobilization of glucose from glycogen stores, primarily in where?, provides a constant supply of how much glucose to all tissues.

Answer 4

Liver
(~5 mM in blood)

Question 5

When glucose is plentiful, such as immediately after a meal, glycogen synthesis accelerates. Yet the liver’s capacity to store glycogen is sufficient to supply the brain with glucose for only about half a day. Under fasting conditions, most of the body’s glucose needs are met by what?

Answer 5

gluconeogenesis (literally, new glucose synthesis) from noncarbohydrate precursors such as amino acids.

Question 6

structure of glycogen? its branched at how many residues

Answer 6

α(1→4)-linked D-glucose with α(1→6)-linked branches every 8–14 (10) residues, highly branched

Question 7

why is it alpha

Answer 7

hydroxyl groups on the bottom

Question 8

How and where are glucose units mobilized,

What allows rapid mobilization of large amounts of glucose

Answer 8

Glucose units are mobilized by their sequential removal from the nonreducing ends of glycogen (the ends lacking a C1-OH group).

remove glucose from non reducing ends

allows rapid mobilization of large amounts of glucose

Question 9

difference between non reducing and reducing end?

Answer 9

reducing end - aldehyde/acetal can be relatively easily oxidized

nonreducing end- not an aldehyde

Question 10

what is glycogenolysis?

Answer 10

the breakdown of glycogen

Question 11

List the three enzymes involved in glycogen degradation and describe the type of reactions they catalyze.

Answer 11

1.Glycogen phosphorylase (or simply phosphorylase) catalyzes glycogen phosphorolysis (bond cleavage by the substitution of a phosphate group) to yield glucose-1-phosphate (G1P)
Leaves a limit branch
2. Glycogen debranching enzyme removes glycogen’s branches, thereby making additional glucose residues accessible to glycogen phosphorylase.

3. Phosphoglucomutase converts G1P to G6P, which has several metabolic fates (

Glucose mobilization in the liver involves a series of conversions from glycogen to glucose-1-phosphate to glucose-6-phosphate and finally to glucose.

Question 12

difference between glycogen phosphorylase a and b

Answer 12

glycogen phosphorylase a at Ser14 is more active
glycogen phosphorylase b is less active it is dephosphrylated

Question 13

Glycogen Debranching Enzyme function?
What does the The α(1 → 6) bond/ branch left behind convert to?
is it slow or faster than glycogen phosphorylase

Answer 13

acts as an 𝛂(1 → 4) transglycosylase/Glucosyltransferase by transfer of an α(1→4)-linked trisaccharide from a limit branch of glycogen to a nonreducing end.

forms a new α(1 → 4) linkage with three more units available for further phosphorolysis.

branch left behind is hydrolyzed and forms glucose instead of G1P

takes glucoses and break them off of branch and add to another chain to form chain long enough for glycogen phosphorylase to continue

debranching much slower than glycogen phopsphorylase reaction

Question 14

Phosphoglucomutase Function

Answer 14

Interconverts Glucose-1-Phosphate and Glucose-6-Phosphate

A phosphoryl group is transferred from the active phosphoenzyme to G1P, forming glucose-1,6-bisphosphate (G1,6P), which then rephosphorylates the enzyme to yield G6P

Question 15

difference between Phosphoglucomutase and phosphoglycerate mutase?

Answer 15

the phosphoryl group in phosphoglucomutase is covalently bound to a Ser hydroxyl group rather than to a His imidazole nitrogen.

Question 16

The fates of G6P.

Answer 16

synthesize glycogen, pentose pathway, or glycolysis

also in liver where it can be converted to glucose for export to tissues via blood

Question 17

why must glycogen synthesis and breakdown occur by separate pathways.

Answer 17

glycogen breakdown is exergonic and the synthesis of glycogen from G1P under physiological conditions is therefore thermodynamically unfavorable without free energy input.

Question 18

• List the three enzymes involved in glycogen synthesis

Answer 18

UDP–glucose pyrophosphorylase, glycogen synthase, and glycogen branching enzyme.

Question 19

UDP–Glucose Pyrophosphorylase function

Answer 19

glycogen biosynthesis requires an exergonic step. This is accomplished, by combining G1P with uridine triphosphate (UTP) in a reaction catalyzed by UDP–glucose pyrophosphorylase.
The product of this reaction, uridine diphosphate glucose (UDP–glucose or UDPG).

Question 20

What is UDPG

Answer 20

an “activated” compound that can donate a glucosyl unit to the growing glycogen chain.

Question 21

Glycogen synthase cannot simply link together two glucose residues; it can only extend an already existing α(1 → 4)-linked glucan chain. How, then, is glycogen synthesis initiated

Answer 21

Glycogen synthase only extends existing chains.
Glycogenin
is glycosylated on a Tyr residue by tyrosine glycosyltransferase. Glycogenin can extend chain by up to seven residues, using UDPG.

Glycogenin Primes Glycogen Synthesis.

Question 22

Glycogen Synthase function?

Answer 22

Extends Glycogen Chains
Glycogen synthase adds glucosyl units to the nonreducing ends of a growing glycogen molecule that has been primed by glycogenin.
Glycogen is extended from a primer built on and by the protein glycogenin.

Question 23

Glycogen Branching Enzyme function for glycogen synthesis?

Answer 23

Glycogen Branching Enzyme Transfers Seven-Residue Glycogen Segments

A branch is created by transferring a 7-residue segment from the end of a chain to the C6-OH group of a glucose residue on the same or another glycogen chain

Glycogen synthase generates only α(1 → 4) linkages to yield α-amylose. Branching to form glycogen is accomplished by this enzyme

Question 24

difference between glycogen synthase a and glycogen synthase b

Answer 24

glycogen synthase a dephosphorylated
is more active

glycogen synthase b phosphorylated
is less active

Question 25

Why is glucose stored in form of glycogen?

Answer 25

To avoid “osmotic stress” (high osmotic pressure).

Osmotic pressure is a colligative property, i.e. it is dependent on the number of dissolved particles, not on their properties (such as size).

Concentration of glycogen in liver cell ≈ 10 nM Concentration of glucose contained in glycogen ≈ 0.4 M

Question 26

The opposing processes of glycogen breakdown and synthesis are reciprocally regulated by what 3 things?

Answer 26

The regulation of glycogen metabolism involves allosteric control as well as hormonal control by covalent modification of the pathway’s regulatory enzymes.
substrate cycling as well

Question 27

What two enzymes in glycogen synthesis and degradation are under allosteric control and covalent modification?

Answer 27

Glycogen Phosphorylase and Glycogen Synthase

Question 28

Why are glycogen synthesis and breakdown controlled?

Answer 28

to make Sure they don’t run simultaneously

Question 29

Glycogen metabolism is ultimately under the control of hormones such as ?

Answer 29

insulin, glucagon, and epinephrine.

Question 30

Both glycogen phosphorylase and glycogen synthase are under allosteric control by effectors that include?

Answer 30

ATP, G6P, and AMP.

Question 31

What is glycogen phosphorylase activated and inhibited by?

Answer 31

Muscle glycogen phosphorylase is activated by AMP and inhibited by ATP and G6P

Question 32

What is glycogen synthase activated and inhibited by?

Answer 32

Glycogen synthase, on the other hand, is activated by G6P.

Question 33

when there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), which is stimulated glycogen phosphorylase or glycogen synthase? How about when when [ATP] and [G6P] are high,

Answer 33

when there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), glycogen phosphorylase is stimulated and glycogen synthase is inhibited, which favors glycogen breakdown. Conversely, when [ATP] and [G6P] are high, glycogen synthesis is favored.

Question 34

The interconversion of the a and b forms of glycogen synthase and glycogen phosphorylase is accomplished through enzyme-catalyzed what?

Answer 34

phosphorylation and dephosphorylation a process that is under hormonal control.

Question 35

What are the effects of phosphorylation and dephosphorylation on glycogen phosphorylase and glycogen synthase? (covalent modification)

Answer 35

glycogen phosphorylase is activated by phosphorylation (b → a), whereas glycogen synthase is inactivated by phosphorylation (a → b). Conversely, dephosphorylation inactivates glycogen phosphorylase and activates glycogen synthase.

Question 36

The cascade that governs the enzymatic interconversion of glycogen phosphorylase involves what three enzymes

Answer 36

1. Phosphorylase kinase, which specifically phosphorylates Ser 14 of glycogen phosphorylase b.
2. Protein kinase A (PKA; Section 13-3C), which phosphorylates and thereby activates phosphorylase kinase. and, thus, stimulates glycogen breakdown)
3. Phosphoprotein phosphatase-1 (PP1; Section 13-2D), which dephosphorylates and thereby deactivates both glycogen phosphorylase a and phosphorylase kinase.

Question 37

What activates PKA

Answer 37

cAMP

Question 38

what activates phosphorylase kinase, therefore , glycogen phosphorylase

Answer 38

Ca 2+binding to calmodulin
and phosphorylation

Ca 2+ triggers muscle contractions, and, by activating glycogen phosphorylase, provides glucose to fuel these contractions

Question 39

Through dephosphorylation, PP1 reduces activity of ?

Answer 39

glycogen phosphorylase and phosphorylase kinase by

Question 40

2 enzymes that regulate glycogen synthase

Answer 40

by PKA and other kinases phosphorylate and thereby inactivate glycogen synthase

Question 41

phosphorylase kinase (which activates glycogen phosphorylase and, thus, stimulates glycogen breakdown) does what to glycogen synthase?

Answer 41

phosphorylates and thereby inactivates glycogen synthase

Question 42

To a large extent, the rates of the phosphorylation and dephosphorylation of these enzymes control glycogen synthesis and breakdown. The two processes are linked by

Answer 42

PKA and phosphorylase kinase, which, through phosphorylation, activate glycogen phosphorylase as they inactivate glycogen synthase.

They are also linked by PP1, which in liver is inhibited by phosphorylase a and therefore unable to activate (dephosphorylate) glycogen synthase unless it first inactivates (also by dephosphorylation) phosphorylase a.

Question 43

Glycogen Metabolism Is Subject to Hormonal Control. Name some of the hormones

Answer 43

Glycogen metabolism is ultimately under the control of hormones such as insulin, glucagon, and epinephrine/adrenaline.

Question 44

What is Gluconeogenesis and where does It occur?

Answer 44

necessary when glucose and glycogen supplies are depleted

• occurs in liver (and kidney)

When dietary sources of glucose are not available and when the liver has exhausted its supply of glycogen, glucose is synthesized from noncarbohydrate precursors (lactate, pyruvate, and amino acids.) by gluconeogenesis.

pyruvate is converted to glucose.

Question 45

The 4 noncarbohydrate precursors that can be converted to glucose include?

Answer 45

the glycolysis products lactate and pyruvate, citric acid cycle intermediates, and the carbon skeletons of most amino acids.

Question 46

What must all the noncarbohydrate precursors convert to very first thing in the reaction? (a citric cycle intermediate)

Answer 46

First, however, all these substances must be converted to the four-carbon compound oxaloacetate (at left), which itself is a citric acid cycle intermediate

Question 47

How is gluconeogenesis related to glycolysis

Answer 47

Gluconeogenesis is mostly the reverse of glycolysis with the pyruvate kinase reaction bypassed by the pyruvate carboxylase and phosphoenolpyruvate carboxykinase reactions, and the phosphofructokinase and hexokinase reactions bypassed by phosphatase reactions.

and

Glycolysis and gluconeogenesis are reciprocally regulated by allosteric effects, phosphorylation, and changes in enzyme synthesis rates.

Pyruvate carboxylase and PEP carboxykinase (PEPCK) bypass pyruvate kinase, fructose-1,6-bisphosphatase (FBPase) bypasses phosphofructokinase, and glucose-6-phosphatase bypasses hexokinase.

Question 48

How is pyruvate converterted to Phosphoenolpyruvate?

Answer 48

by first converting the pyruvate to oxaloacetate.
1. Pyruvate carboxylase catalyzes the ATP-driven formation of oxaloacetate from pyruvate and HCO 3 − .

2. PEP carboxykinase (PEPCK) converts oxaloacetate to PEP in a reaction that uses GTP as a phosphoryl-group donor.

Pyruvate Carboxylase Has a Biotin Prosthetic Group

Question 49

What is the problem that occurs when trying to synthesize oxaloacetate?

Answer 49

Glycolysis and gluconeogenesis occur in cytosol, oxaloacetate is produced in mitochondrion.

No transporter for oxaloacetate across the inner mitochondrial membrane exists.

Gluconeogenesis Requires Metabolite Transport between Mitochondria and Cytosol.

Question 50

How is Gluconeogenesis regulated

Answer 50

Gluconeogenesis is regulated by changes in enzyme synthesis and by allosteric effectors, including fructose-2,6-bisphosphate (F2,6P), which inhibits FBPase and activates phosphofructokinase (PFK) and whose synthesis depends on the phosphorylation state of the bifunctional enzyme phosphofructokinase-2/fructose bisphosphatase-2 (PFK-2/FBPase-2).

Question 51

Long-term regulation also occurs via changes in the amounts of certain enzymes. Transcription rates can be affected by hormones.

Question 52

Other Carbohydrate Biosynthetic Pathways

Answer 52

O and N-linked oligosaccharides

Question 53

Formation of glycosidic bond requires?

Answer 53

nucleotide sugars/energy:

Question 54

How are O-Linked oligosaccharides synthesized?

Answer 54

O-Linked oligosaccharides are synthesized by the sequential addition of sugars to a protein.

Question 55

How are N-Linked oligosaccharides synthesized?

Answer 55

• N-Linked oligosaccharides are assembled on a dolichol carrier and then transferred to a protein.
• attached to Asn