pyruvates fate via lactate DH: RXN 11

Question 1

LDH

Answer 1

at eq, can go eithe way.
tetrameric with several isoforms

properties vary w tissue.
Heart do it better in reverse: this is an anaerobic process, do not want. WHy go backwards? Cori cycle = send lactate back to liver to convert to glucose to send to muscles to use
Heart uses lactate to make pyruvate and send it through aerobic oxidation.

Question 1

How is NADH involved in rxn 11

Answer 1

NADH’s pro-R hydride adds to the re-face of pyruvate at C2, and will get a concurrent proton transfer from His to the previous C=O which is now an alkoxide and will become OH. (body needs a proton source for acid workup step, this is what His provides)

NADH becomes NAD+ to be used by GAPDH

Question 2

His proton transfer

Answer 2

His proton transfer (GAC) is aided by the destabilizing repulsive interactions occurring between the positive charges of His and Arg being close together.

The proton transfer removes this destabilizing interaction

Question 3

Two Arg functions

Answer 3

Arg 109 - involved in the destabilizing interaction
Arg 109 and 117 involved in salt bridges (ES + H bonds) which orient pyruvate correctly to remove respulsive interactions

Question 4

four catalytic types

Answer 4

Orientation
GABC
ES
proximity

Question 5

Hydride and proton sources

Answer 5

proton - histidine
hydride - nadh