lec 12: glycogen metabolsim

describe the structure of glycogen

• has multiple ends because of branching

• all sugars have alpha 1 → 4 linkages

• the branching adds alpha 1 → 6 linkages

• there is a protein core called glycogenin

what enzymes are involved in glycogen synthesis?

• phosphoglucomutase

• UDP-glucose phorphorylase

• glycogen synthase

• branching enzyme

what does phosphoglucomutase do?

convert G6P to G1P (and the reverse reaction)

reaction by UDP-glucose phorphorylase

• substrate

• enzyme

• product

• purpose

• substrate: G1P, UTP

• enzyme: UDP-glucose phosphorylase

• product: UDP-glucose, pyrophosphate which will then get hydrolyzed to two phosphates, the energy from this hydrolysis drives the entire reaction forward (makes the reaction favourable)

• purpose is to activate glucose

mechanism of UDP-glucose phorphorylase

1. an oxygen on the phosphate of glucose-1-P attacks the alpha phosphate’s phosphorous atom on UDP

2. get UDP-glucose which goes to next reaction and get pyrophosphate which hydrolyzes spontaneously

reaction by glycogen synthease

• substrate

• enzyme

• product

• regulated?

• substrate: UDP-glucose and the existing glycogen chain

• enzyme: glycogen synthease

• product: glycogen chain and UDP

• yes this reaction is regulated by covalent modification (eg. phosphorylation)

mechanism of glycogen synthase

• glucose of UDP-glucose will act as a nucleophile and attack the free end of the glycogen chain

• it joins the chain and UDP is kicked off

what are the enzymes involved in glycogen degradation

• glycogen phosphorylase

• debranching enzyme

• phosphoglucomutase

reaction by glycogen phosphorylase

• substrate

• cofactor

• product

• regulated?

• favourable?

• substrate: glycogen, Pi

• cofactor: PLP (pyridoxal phosphate)

• product: G1P, rest of glycogen chain

• most heavily regulated step in glycogen metabolism

• delta G is almost zero so it is favourable enough

mechansim by glycogen phosphorylase

1. PLP takes a H from phosphate to activate phosphate as a nucleophile

2. phosphate now attacks the anomeric carbon of the branch glucose and breaks the bond

3. glucose-1-phosphate is released

explain the role of debranching enzyme

• debrancing enzyme transfers most of the glucoses to another branch (yellow ones in the picture)

• this leaves one glucose (the pinkn one) on the branch so it is easily taken off/hydrolyzed

explain how glycogen phosphorylase is regulated

• the T form (tight/taught) is inactive and preferred if not phosphorylated

• R form (relaxed) is active and preferred when phosphorylated

• phosphorylase kinase and phosphoprotein phosphatase do covalent modifications to change the enzyme EQM

• allosteric regulation:

  • ATP and G6P inhibit the enzyme as they indicate higher energy levels so we dont need glycogen degradation

  • AMP activates the enzyme because it indicates energy levels are low

coordinated control of glycogen metabolism

• phosphorylation changes the conformation of the enzymes such that one is preffered over the other

• phosphorylase b is inactive when unphosphorylated

• because active form: phorphorylase a when it is phosphorylated

• synthase D is inactive when phosphorylated and active synthase a when dephosphorylated

• phosphorylated are done by kinase

• dephosphorylations are done by phosphatase