Question

35) The overall reaction of glyceraldehyde 3-phosphate dehydrogenase (GAP glyceraldehyde 3-phosphate + NAD+ + P = 1,3-bisphosphoglycerate + NADH GAPDH couples together two reactions with favorable (AG'°-50 kj/mol) and unfavorable (AG' +50 kJ/mol) Gibbs free energies, respectively. a) (6 pts) Write the balanced chemical equations for the two separate reactions. b) (6 pts) Draw the structure of the thiohemiacetal intermediate and show the mechanism for generating the acyl thioester intermediate. 36) (4 pts) Under anaerobic conditions, lactic acid fermentation regenerates NAD by reducing pyruvate. Draw the hydride transfer mechanism to form lactate.

Answer 1

Multiple question as per guideline only first will be answered:

35). Reaction of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

Glyceraldehyde 3-phosphate + NAD⁺ + Pi  $\rightleftharpoons$  1,3-Bisphosphoglycerate + NADH + H⁺

a)

GADPH couples one favourable reaction with unfavourable one. Aldehyde group of glyceraldehyde 3-phosphate is oxidized, not to a free carboxyl group but to a carboxylic
acid anhydride with phosphoric acid, this anhydride has a very high standard free energy of hydrolysis. Free energy of oxidation of the aldehyde group of glyceraldehyde 3-phosphate is conserved by formation of the acyl phosphate group at C-1 of 1,3-bisphosphoglycerate.

i). Fructose 1,6-bisphosphate   $\rightleftharpoons$ Glyceraldehyde 3-phosphate + Dihydroxyacetone phosphate

  $\Delta$G'⁰ = +ve

ii)1,3-Bisphosphoglycerate + ADP  $\rightleftharpoons$​​​​​​​ 3-Phosphoglycerate + ATP     $\Delta$G'⁰​​​​​​​ = -ve

b) Aldehyde group of glyceraldehyde 3-phosphate reacts with the -SH group of Cys residue producing a thiohemiacetal, which is reduces NAD+ to give acyl thio-ester.

Qi, CHOPO ICHOPO 20 1 CH₂ OPO20 OPOZO -H a duopo 20 & c сири Kig AQOH d=0 Che =0 l on HOW DHAP) aldolall CHOPO, 20 SAL-3-0 Chon oso -50kJ/mol wo 0,40039 +ADP (40P020 Ga, Poz CHOH +ADP mest + ATP u-o e 06:04 (40P02 CHLOH Mot Bao -50kJ/mol b) Thisheriacetal intemediate CHOPO 20 태매 H-c-oo s-cys intermediate Generation of the este azyl сц, оро, NADH CHOP GRO NADT CHOH -NH CHOM 2=0 seys is scus (Aly thioester)