Glucose metabolism (lecture 28)

Question 1

what are the main storage molecules

Answer 1

starch in plants

glycogen in animals

Question 2

what is glycogen?

Answer 2

highly branched homopolysaccharide

Question 3

structure of glycogen

Answer 3

glucose in chains is joined by alpha-1,4-glycosidic bonds
branch points every 10 residues
branch points created by alpha-1,6-glycosidic bonds

Question 4

what are the 4 key steps in the glycogenesis?

Answer 4

diversion
activation
polymerisation
branching

Question 5

what is glycogenesis?

Answer 5

creation of glycogen

Question 6

what happens in diversion in glycogenesis?

Answer 6

phosphate is moved from C6 to C1
glucose-6-phosphate to glucose-1-phosphate

phosphoglucomutase used

Question 7

what happens in activation in glycogenesis?

Answer 7

glucose-1-phosphate to UDP-glucose

2 phosphates removed from UTP
UMP then joins to glucose-1-phosphate
UDP-glucose pyrophosphorylase used

Question 8

what happens in polymerisation in glycogenesis?

Answer 8

UDP-glucose to glycogen
glycogen synthase used

sugar molecules added to the non reducing end

Question 9

what happens in branching in glycogenesis?

Answer 9

only molecule has 10 residues new branches can be made
large branching enzyme needed
= amylo-(1,4–>1,6)-transglycolase

going from a 1,4 to a 1,6 linkage

Question 10

how does amylo-(1,4–>1,6)-transglycolase work?

Answer 10

breaks existing molecules between 6th and 7th link

moves the 6 glucose molecules across and adds them between the 8th and 9th glucose residues on the previous chain

glycogen synthase can then add more glucose molecules to non-reducing end

Question 11

what does glycogen synthase require in order to work?

Answer 11

glycogenin

Question 12

what is glycogenin?

Answer 12

initiator molecule of glycogen formation
acts as a primer / co-factor

when in close proximity glycogen formation occurs
the further away they are the slower the reaction pathway is

Question 13

what is glycogenolysis?

Answer 13

breakdown of glycogen

Question 14

4 stages in glycogenolysis?

Answer 14

erosion of chain ends
debranching
recovery
release

Question 15

how are chain ends eroded in glycogenolysis?

Answer 15

by glycogen phosphorylase
vitamin B6 donates phosphate group

sugar chain fits in the active site and chops off 1 glucose at a time
but it can only go so far
stops at the 4th glucose-1-phosphate

Question 16

how does debranching occur in glycogenolysis?

Answer 16

uses a debranching enzyme which has 2 active sites

1st = alpha-(1-->4)-transglycosylase 
2nd = alpha-(1-->6)-glucosidase

Question 17

what does alpha-(1–>4)-transglycosylase do?

Answer 17

1st debrancher enzyme

transfers glycogen from C1 to C4
makes glycogen molecule longer
now have 1 glucose molecule that needs to be removed
• if nit removed, enzyme cannot function properly

Question 18

what does alpha-(1,6)-glucosidase do?

Answer 18

2nd debrancher enzyme

breaks alpha-1,6-glycosidic link releasing free glucose

glycogen phosphorylase can now fit again and can continue to breakdown glycogen

Question 19

what happens in recovery in glycogenolysis?

Answer 19

glycogen-1-phosphate cannot be used to make new glycogen
cannot be used to make ATP or new glucose

phosphoglucomutase repositions phosphate group to C6
glucose-1-phosphate to glucose-6-phosphate

Question 20

what happens in release in glycogenolysis?

Answer 20

in muscle, glucose-6-phosphate is mobilised and used for glycolysis within the muscle

in liver, glucose-6-phosphate is converted back to glucose and is released into the bloodstream to be respired by other tissues

Question 21

what does insulin do?

Answer 21

promotes glycogenesis

formation of glycogen

Question 22

what does glucagon do?

Answer 22

promotes glycogenolysis

breakdown of glycogen

Question 23

symptoms of glycogen storage diseases (GSD) ?

Answer 23

muscle cramp 
muscle weakness 
tiredness 
hypoglycaemia 
hepatomegaly - enlargement of the liver

Question 24

what is type 0?

Answer 24

liver glycogen synthase deficiency

glucose-1-phosphate ≠ glycogen

results in hyperglycaemia

Question 25

what is type 1?

Answer 25

glucose-6-phosphate deficiency
Von Gurke’s disease

glucose-6-phosphate ≠ glucose

results in hypoglycaemia & hepatomegaly

Question 26

what is type 3?

Answer 26

alpha-1,6-glucosidase deficiency
Coris disease

second active site of the debrancher enzyme
glycolysis blocked at the branches

results in hypoglycaemia & hepatomegaly

Question 27

what is type 4?

Answer 27

amylo-(1,4–>1,6)-glucosidase deficiency
Andersens disease

brancher enzyme
long glycogen chain formed with no branches
water insoluble
glucose release is insufficiently fast

results in hypoglycaemia & hepatomegaly

Question 28

what is type 5?

Answer 28

muscle phosphorylase deficiency
McArdles disease

releases terminal sugars
muscle requirements not met during exercise