12 - Glycogen Metabolism

Question 1

what is glycogenesis?

Answer 1

synthesis of glycogen from glucose

Question 2

what is glycogenolysis?

Answer 2

breakdown of glycogen to form glucose

Question 3

what is gluconeogenesis?

Answer 3

de novo (new) synthesis of glucose from metabolic precursors (lactate, amino acids, glycerol)

Question 4

what is glycogen purpose?

Answer 4

main storage of glucose in liver & muscle

Question 5

what process if the primary source of glucose overnight?

Answer 5

gluconeogenesis = when hepatic glycogen is depleted

Question 6

what is the most efficient way to store glycogen?

Answer 6

if it is branched - by alpha 1-6 glycosidic links

Question 7

what does glycogen consist of?

Answer 7

glycogen = polymer consisting of glucose molecules (joined by alpha 1-4 glycosidic link)

• branches are introduced by alpha 1-6 glycosidic link

Question 8

what is required for glucose residues to be added to existing glycogen chain?

Answer 8

= they need to be primed

A glycogen ‘primer’ is required = This primer is a short chain of glucose residues, typically containing at least four glucose molecules

primer = covalently attached to a protein called glycogenin

Question 9

describe glycogen synthesis?

Answer 9

1. hexokinase catalyses glucose -> glucose-6-phosphate (step from glycolysis)
2. phosphoglucomutase catalyses glucose-6-phosphate -> glucose-1-phosphate
3. UDP-glucose pyrophosphorylase catalyses glucose-1-phosphate to UDP-glucose
4. glycogen synthase catalyses UDP glucose to [glucose]n+1 which is prime substrate that then makes glycogen

Question 10

what enzyme catalyses re-assignement of glucose molecule from 6th position to 1st position and why does it do this?

Answer 10

phosphoglucomutase

• by re-assigning glucose molecule to 1st position within glycogen chain it’s no longer readily available for glycolysis (break down of glucose for energy) = glycogen acts as storage from of glucose

Question 11

what provides necessary energy for conversion in glycogenesis?

Answer 11

exchange for ATP, UDP can be exchanged for ATP during process of making UDP glucose, this provides the necessary energy for this conversion

= phosphate ester linkage in a nucleotide sugar releases free energy on hydrolysis

Question 12

what is the primer in glycogen synthesis?

Answer 12

addition of glucose molecules requires a primer which is short chain of glucose residues (UDP), involves converting UDP→UTP, which serves as the prime substrate for the synthesis of the glycogen polymer

Question 13

what are activated forms of
a) glucose
b) phosphate
c) acetate

Answer 13

a) UDP
b) ATP
c) acetyl-CoA

Question 14

what is rate limiting enzyme of glycogenesis?

Answer 14

glycogen synthase - catalyses the transfer of a glucose molecule from UDP-glucose to the growing glycogen chain

Question 15

what is process of glycogenolysis?

Answer 15

1. glycogen phosphorylase catalyses glycogen -> glucose-1-phosphate
2. phosphoglucomutase catalyes glucose-1-phosphate to glucose-6-phosphate
3. glucose 6 phosphotase catalyses reaction to glucose

Question 16

why does glucose-6-phosphatase need to remove phosphate in 6th position in glycogenolysis?

Answer 16

phosphoglucomutase = shifts to 6th position so glucose 6 phosphatase removes phosphate in 6th position to make glucose that can be transported out cell. from blood to liver via GLUT2 transporter

• glucose with phosphate in 6th position is one in a form of glucose that is primed and ready to enter glycolysis = breakdown of glucose to make energy (metabolism)
• glucose-6-phosphate will want to branch and make glycogen and that’s not what you’re wanting to do here

Question 17

what is the rate limiting step of glycogenolysis?

Answer 17

glycogen -> glucose-1-phosphate catalysed by glycogen phosphorylase
(as 1 glucose molecule cleaved off end of glycogen at a time)

Question 18

what happens to glucose-6-phosphate
a) in liver?
b) in skeletal muscle?

Answer 18

a) glucose 6-phosphate can be de-phosphorylated and the resulting glucose released into the blood stream

b) glucose 6-phosphate CANNOT be de-phosphorylated but instead is used to provide energy via glycolysis and the TCA cycle

Question 19

what are examples of precursors that make glucose in gluconeogenesis and where do these precursors come from?

Answer 19

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 20

where does energy for gluconeogenesis come from?

Answer 20

from oxidation of fatty acids released from adipose tissue

Question 21

where does gluconeogenesis occur?

Answer 21

mainly in the liver, small amounts in the kidneys

Question 22

what is general idea of process of gluceogenesis?

Answer 22

it’s basically the formation of glucose from amino acids, lactate and glycerol etc when in starvation

• it proceeds via the synthesis of oxaloacetate in mitochondria which is TCA cycle intermediate = there are actually lots of amino acid precursors that are involved in TCA cycle making it the coordination centre for drawing carbon and then repurposing it (for energy)

Question 23

what are the 4 unique liver enzymes that involved in gluconeogenesis?

Answer 23

1. pyruvate carboxylase
2. PEP carboxykinase (phosphoenolpyruvate)
3. fructose-1,6-bisphosphatase
4. glucose-6-phosphatase

= Gluconeogenesis is NOT the reverse of glycolysis due to the need to overcome energetically unfavourable steps, catalysed by a unique set of enzymes - these are the unique enzymes that allow reaction to occur

Question 24

what do the 4 unique enzymes of gluconeogenesis catalyse? (what steps)

Answer 24

1. pyruvate carboxylase = catalyses pyruvate →oxaloacetate
2. PEP carboxykinase (phosphoenolpyruvate) = catalyses oxaloacetate →phosphoenolpyruvate (PEP)
3. fructose-1,6-bisphosphatase = catalyses hydrolysis of fructose-1,6-bisphosphate →fructose-6-phosphate
4. glucose-6-phosphatase = catalyses glucose-6-phosphate →glucose

Question 25

is fructose-2,6-biphosphate high or low in
a) fed state?
b) starved state?

Answer 25

a) high
b) low

Question 26

what does high AMP and ADP mean?

Answer 26

high energy