Glycogen Metabolism

Question 1

glycogenesis

Answer 1

synthesis of glycogen from glucose

Question 2

glycogenolysis

Answer 2

breakdown of glycogen to form glucose via phosphorolysis

levels fluctuates, dependent upon meal times

Question 3

gluconeogenesis

Answer 3

de novo synthesis of glucose from metabolic precursors (lactate, amino acids, glycerol)
primary source of glucose overnight when hepatic glycogen depleted

Question 4

what is glyocgen

Answer 4

main storage form of glucose in liver and muscle cells

Question 5

liver glycogen

Answer 5

main site of glycogen storage

broken down between meals and released to maintain blood glucose levels for red blood cells and the brain

Question 6

muscle glycogen

Answer 6

not available for maintenance of blood glucose levels

provides energy via glycolysis and the TCA (Krebb’s cycle) during bursts of physical activity

Question 7

structure of glycogen

Answer 7

polysaccharide (polymer) - multiple molecules of glucose linked together via alpha 1-4 glycosidic links
branches are introduced by alpha 1-6 glycosidic links

Question 8

priming glycogen

Answer 8

glucose residues can only be added to a existing glycogen chain
a glycogen primer containing at least 4 glucose residents is required
the primer is covalently attached to a protein called glycogenin

Question 9

glycogen synthesis

Answer 9

PP
glucose converted to glucose-6-phosphate via hexokinase
glucose-6-phosphate converte to glucose-1-phosphate via phosphoglucomutase (specific to liver)
glucose-1-phosphate converted to UDP-glucose via UDP-glucose pyrophosphorylase
UDP-glucose converted to glycogen via glycogen synthase

ATP hydrolyses UDP to UTP to supply energy and form UDP-glucose

Question 10

describe UDP-glucose

Answer 10

simple precursors are first converted to activated intermediates
UDP-glucose is an activated form of glucose
phosphate ester linkage in nucleotide sugar releases free energy on hydrolysis

Question 11

describe glycogen-synthase

Answer 11

synthesis glycogen from UDP-glucose
adds one glucose molecule to glycogen at a time - can only extend chains (not being new ones or introduce branches)
rate limiting enzyme of glycogenesis

Question 12

how is a alpha 1-6 glycosidic branch introduced to glyocgen

Answer 12

via a branching enzyme - transglycosylase

every 10 glucose residues

Question 13

what catalyses glycogenoylsis

Answer 13

glycogen phosphorylase;
rate limiting step
one glucose molecule cleaved off the ends of glycogen at a time
glucose-1-phosphate converted to glucose-6-phosphate

de-branching will require additional enzymes

Question 14

glycogenolysis in the liver

Answer 14

glucose-6-phosphate can be de-phosphorylated and the resulting glucose (3 molecules) released into the bloodstream

Question 15

glycogenolysis in skeletal muscle

Answer 15

glucose-6-phosphate cannot de de-phosphorylated

instead it is used to provide energy via glycolysis and the TCA cycle

Question 16

steps of glycogenolysis

Answer 16

glycogen converted to glucose-1-phosphate via glycogen phosphorylase
glucose-1-phosphate converted to glucose-6-phosphate via phosphoglucomutase
glucose-6-phosphate used for glycolysis or converted to glucose to be transported around the blood via GLUT2 transporter (liver only)

Question 17

precursors of gluconeogenesis

Answer 17

lactate - synthesised by skeletal muscle under anaerobic conditions
amino acids - derived from muscle protein by proteolysis
glycerol - derived from triglycerides by lipolysis in adipose tissue

Question 18

energy for gluconeogenesis

Answer 18

from oxidation of fatty acids released from adipose tissue

Question 19

location of gluconeogenesis

Answer 19

mainly in liver

small amounts in kidney

Question 20

steps of gluconeogenesis

Answer 20

requires 4 unique liver enzymes
proceeds via the synthesis of oxaloacetate in mitochondria;
TCA cycle intermediate which accepts acetyl groups
important for accepting acetyl groups from fat breakdown
energy consuming - ATP hydrolysis drives unfavourable reaction;
4ATP + 2GTP –> 4ADP + 2GDP (*PP)

Question 21

describe the Cori cycle

Answer 21

lactate as a precursor of gluconeogenesis - formed in twitch muscle under conditions of heavy exercise
blood transports lactate to liver
liver converts lactate back to glucose
glucose released into bloodstream
shifts metabolic burden from muscle to other organs

Question 22

reciprocal regulation of glycolysis and gluconeogenesis

Answer 22

hormonal regulation (both pathways) - glucagon, insulin

adrenaline and cortisol influence glycogenolysis

high AMP or ADP - low energy
high ATP - high energy
fructose 2,6 biphosphate - high in fed state, low in starved state
citrate, alanine, acetyl-CoA - high when intermediates or building blocks abundant

Question 23

glycogen storage disease

Answer 23

group of diseases with increased glycogen deposits in liver or muscle or both
10 different types - each one due to defect/mutation in different enzyme