metabolic pathway of glycogen

Question 1

glycogenesis

Answer 1

synthesis of glycogen from glucose

Question 2

glycogenolysis

Answer 2

breakdown of glycogen to form glucose

Question 3

gluconeogenesis

Answer 3

synthesis of glucose from metabolic precursors ie lactate/amino acids/glycerol

Question 4

what is glycogen

Answer 4

the main storage of glucose in liver and muscle cells
*liver glycogen s broken down between meals and released to maintain blood glucose levels - muscle is more for physical activity

Question 5

what are the sources of blood glucose

Answer 5

> glycogenolysis fluctuates dependent upon meal times

>gluconeogenesis is the primary source of glucose overnight when hepatic glycogen is depleted

Question 6

the difference between glycogen of glycogenin

Answer 6

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

Question 7

glycogen synthesis

Answer 7

> glucose becomes glucose-6-phosphate through the action of HEXOKINASE
6-phosphate then becomes glucose-1-phosphate via PHOSPHOGLUCOMUTASE
this then becomes UDP-glucose as it binds with UTP converted from UDP via ATP, it binds via the action go glycogen synthase
this then is converted into glycogen as another molecule of glucose is added and UTP is removed

Question 8

UDP glucose

Answer 8

“uridine diphosphate glucose”
>simple precursors are first converted to activated intermediates
>UDP can be thought of as an activated form of glucose - ATP and acetyl-CoA are activated forms of phosphate and acetate
>the phosphate ester linkage in a nucleotide sugar releases free energy on hydrolysis

Question 9

glycogen synthase

Answer 9

this synthesis glycogen from UDP-glucose
>adds one glucose molecule to glycogen at a time
>can only extend the chains of glycogen
>cannot introduce branches
>is a rate limiting enzyme of glycogenesis

** the branching enzyme - a transglycosylase - introduces alpha 1-6 glycosidic branches into glycogen

Question 10

glycogenolysis

Answer 10

catalysed by glycogen phosphorylase
>a rate limiting step of glycogenolysis
>one glucose molecule is cleaved off the ends of glycogen at a time
>glucose-1-phopshate is then converted to glucose-6-phosphate

> > in the liver 6-phosphate can be de-phosphorylated and the resulting glucose released into the blood stream
in skeletal muscle 6-phosphate cannot be dephosphorylated but instead is used to provide energy via glycolysis and the TCA cycle
debranching requires additional enzymes

Question 11

glycogen breakdown

Answer 11

glycogen becomes glucose-1-phosphate via the action of glycogen phosphorylase (this is the rate limiting step)
>1-phosphate becomes 6-phosphate via the action of phosphoglucomutase
>from this it can become glucose (in the liver) via glucose-6-phosphatase or undergoes glycolysis

Question 12

gluconeogenesis

Answer 12

> it is the synthesis of glucose within the body from precursor substrates
during prolonged starvation new glucose has to be synthesised
precursors include: lactate, amino acids, glycerol
energy comes from oxidation of fatty acids released from adipose tissue
location = in the liver mainly and small amounts in the kidney

*is not the reverse of glycolysis due to the need to overcome energetically unfavourable steps catalysed by a unique set of enzymes

Question 13

glycolysis

Answer 13

there are three essentially irreversible reactions:
hexokinase
phosphofructokinase
pyruvate kinase
>several special reactions are required to bypass the irreversible reactions

Question 14

gluconeogenesis 2

Answer 14

> requires four unique liver enzymes
proceeds via the synthesis of oxaloacetate in mitochondria
-the TCA cycle intermediate which accepts acetyl groups
-important for accepting acetyl groups from fat breakdown
energy consuming

Question 15

stoichiometry of gluconeogenesis

Answer 15

2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H+ + 6 H2O
»»»»»
glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+

energetically expensive
>ATP hydrolysis drives an unfavourable reaction

Question 16

the Cori cycle

Answer 16

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

Question 17

amino acids

Answer 17

derived from muscle protein under proteolysis

ie citric acid cycle

Question 18

reciprocal regulation of glycolysis and gluconeogenesis

Answer 18

regulation via hormones : glucagon and insulin

> high AMP or ADP means low energy
High ATP means high energy
fructose 2,6 - biphosphate is high in fed state and low in starved state
citrate, alanine, acetyl-CoA is high when intermediated or building blocks are abundant

Question 19

glycogen storage disease

Answer 19

groups of diseases with increased glycogen deposits in liver or muscle or both
>there are at least 10 different types (each one due to a defect in a different enzyme)