Glycogen Metabolism Flashcards
glycogen contains which 2 kinds of bonds?
(a-1,4) linkages and (a-1,6) linkages
which end does glycogen degradation and synthesis occur?
non reducing ends
what does glycogen phosphorylase do?
cleaves (a-1,4) linkages until it reaches the 4th from the branch point
(directly phosphorylates the glucose to make G1P)
what does debranching enzyme transferase do?
transfers a block of 3 units to the nonreducing end of the chain
what does debranching enzyme (a-1,6) glucosidase do?
cleaves the last remaining (a-1,6) linked glucose
what does phosphoglucomutase do?
interconverts between glucose-1-P (G1P) and glucose-6-P (G6P)
what is PLP (pyridoxal-5-phosphate)?
a derivate of vitamin B6 and cofactor for glycogen phosphorylase
what is the mechanism of PLP?
the phosphate of PLP is involved in acid/base catalysis and covalently binds to a lysine residue in glycogen phosphorylase
what is 1,5-gluconolactone?
competitive inhibitor of glycogen phosphorylase (mimics its structure)
what helps phosphoglucomutase interconvert between G1P and G6P?
a phosphorylated serine helps in phosphate exchange
what are the 3 key steps of glycogenesis?
- activation of glucose
- formation of an a-1,4 bond
- formation of an a-1,6 bond
what is the UDP-glucose-pyrophosphorylase equation?
G1P + UTP = UDP-glucose + PPi
where does G1P come from?
phosphoglucomutase
what other modifications are used to “activate” metabolites?
- acetyl CoA ~ acetate
- ATP ~ Pi
what is the glycogen synthase equation?
UDP-glucose + glycogen(n) —> glycogen(n+1) + UDP
what does glycogen synthase do?
- makes linear glucose chains
- forms a-1,4 glyosidic bonds at non-reducing ends
- resulting in linear enlargement of an existing glycogen molecule
what is glycogenin?
- primer for glycogen synthase
- autocatalytic tyrosine glycosyl transferase
- the enzyme is the substrate
what does branching enzyme do?
- cleaves a a-1,4 bond to yield a 7-unit chain
- forms an a-1,6 bond between 7-unit chain and another glycosyl unit
what does glycogenesis require and how much?
- energy
- enzymatically rephosphorylating UDP costs an ATP (1 G6P in glycogen = 1 ATP)
fasting stimulates which type of pathways?
glucagon stimulates catabolic pathways, and often inhibits anabolic pathways
eating stimulates which type of pathways?
insulin drives glucose into cells and stimulates anabolic pathways, and often inhibits catabolic pathways
what are the steps to breakdown glycogen?
- glucagon activates a GPCR
- that stimulates adenylate cyclase to make cAMP
- that activates PKA (protein kinase A)
- results in a phosphorylation cascade ultimately phosphorylating and activating glycogen phosphorylase
how is glycogen synthesized?
high glucose/insulin promotes…
- dephosphorylation and activation via PP1
- allosteric activation by upregulating G6P
what inhibits glycogen synthase?
PKA
true or false: phosphoglucomutase is unidirectional
false, it is bidirectional and sensitive to G6P levels
what causes upregulation of G6P and which process does it lead to?
fed state leads to upregulation of G6P causing glycogenesis
what causes downregulation of G6P and which process does it lead to?
fasted state leads to downregulation of G6P causing glycogenolysis
what is the last step of glycogenolysis?
phosphoglucomutase
describe type 1: Von Gierke’s disease
- Glucose-6-phosphotase deficiency
- leads to glycogen accumulation in the liver and kidneys
what is the role of glycogen in the liver?
dephosphorylation -> glucose -> export
what is the role of glycogen in skeletal muscle?
- glycolysis -> pyruvate -> ATP
OR - PPP -> NADPH, R5P
this is because skeletal muscle is usually recruited during exercise, where we need energy fast
