Glucose metabolism (lecture 28) Flashcards
what are the main storage molecules
starch in plants
glycogen in animals
what is glycogen?
highly branched homopolysaccharide
structure of glycogen
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
what are the 4 key steps in the glycogenesis?
diversion
activation
polymerisation
branching
what is glycogenesis?
creation of glycogen
what happens in diversion in glycogenesis?
phosphate is moved from C6 to C1
glucose-6-phosphate to glucose-1-phosphate
phosphoglucomutase used
what happens in activation in glycogenesis?
glucose-1-phosphate to UDP-glucose
2 phosphates removed from UTP
UMP then joins to glucose-1-phosphate
UDP-glucose pyrophosphorylase used
what happens in polymerisation in glycogenesis?
UDP-glucose to glycogen
glycogen synthase used
sugar molecules added to the non reducing end
what happens in branching in glycogenesis?
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
how does amylo-(1,4–>1,6)-transglycolase work?
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
what does glycogen synthase require in order to work?
glycogenin
what is glycogenin?
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
what is glycogenolysis?
breakdown of glycogen
4 stages in glycogenolysis?
erosion of chain ends
debranching
recovery
release
how are chain ends eroded in glycogenolysis?
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
how does debranching occur in glycogenolysis?
uses a debranching enzyme which has 2 active sites
1st = alpha-(1-->4)-transglycosylase 2nd = alpha-(1-->6)-glucosidase
what does alpha-(1–>4)-transglycosylase do?
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
what does alpha-(1,6)-glucosidase do?
2nd debrancher enzyme
breaks alpha-1,6-glycosidic link releasing free glucose
glycogen phosphorylase can now fit again and can continue to breakdown glycogen
what happens in recovery in glycogenolysis?
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
what happens in release in glycogenolysis?
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
what does insulin do?
promotes glycogenesis
formation of glycogen
what does glucagon do?
promotes glycogenolysis
breakdown of glycogen
symptoms of glycogen storage diseases (GSD) ?
muscle cramp muscle weakness tiredness hypoglycaemia hepatomegaly - enlargement of the liver
what is type 0?
liver glycogen synthase deficiency
glucose-1-phosphate ≠ glycogen
results in hyperglycaemia
what is type 1?
glucose-6-phosphate deficiency
Von Gurke’s disease
glucose-6-phosphate ≠ glucose
results in hypoglycaemia & hepatomegaly
what is type 3?
alpha-1,6-glucosidase deficiency
Coris disease
second active site of the debrancher enzyme
glycolysis blocked at the branches
results in hypoglycaemia & hepatomegaly
what is type 4?
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
what is type 5?
muscle phosphorylase deficiency
McArdles disease
releases terminal sugars
muscle requirements not met during exercise
