Coenzyme A Pantothenate 2 mercaptoethylamine ADP Acyl carrier

Coenzyme A Pantothenate 2 -mercaptoethylamine ADP Acyl carrier protein ser - protein

Fritz Lipmann Noble prize for Chemistry 1953 (shared with Sir Hans Krebs) "for his discovery of co-enzyme A and its importance for intermediary metabolism" 1899 -1986

Pyruvate dehydrogenase The core of the complex consists of 60 copies of E 2. At the periphery of the complex are: w 30 copies of E 1 (itself a tetramer with subunits a 2 b 2) w 12 copies of E 3 (a homodimer), plus 12 copies of an E 3 binding protein that links E 3 to E 2.

Pyruvate dehydrogenase OH O 1. H 3 C-C-COO- + H+ + E 1 TPP-CH O + TPP-CH S S E 2 CH 3 S – C –CH 3 SH E 2 O 3. S – C –CH 3 SH E 2 CO 2 CH 3 OH 2. + + Co. A-SH E 2 + H+ O Co. A-S - C –CH 3 + E 2 Acetyl Co. A 4. 5. E 2 SH SH E 3 - FADH 2 + + E 3 -FAD NAD E 2 S S E 3 - FAD + + E 3 - FADH 2 NADH + H+ SH SH

Regulation of PDH: 1. Inhibited by Ac. Co. A and NADH ¯ Ac. Co. A (competes with Co. A for E 2), NADH (competes with NAD for E 3) 2. Regulated by phosphorylation E 2 is associated with PDH kinase and PDH phosphatase which act on E 1 · phosphorylation of the E 1 subunit inhibits · dephosphorylation activates. · Phosphorylation controled by NADH/NAD, Ac. Co. A/Co. A and ATP/ADP. Increasing these ratios promotes phosphorylation and hence decreases activity. THEREFORE: Phosphorylation of E 1 increases and activity of PDH decreases when energy charge is high. · Pyruvate inhibits PDH kinase in the presence of high [ADP] and therefore promotes dephosphorylation and increase in activity. · In muscle high [Ca 2+] activates phosphatase. At onset of exercise [Ca 2+], pyruvate and ADP increase resulting in increased PDH phosphatase (Ca) and decrease PDH kinase due to increased pyruvate + ADP, and decreased ATP/ADP ratio.

Sir Hans Krebs Noble Prize for Chemistry "for his discovery of the citric acid cycle" 1900 - 1981

or GTP

O HO COO- SCo. A C C COO- C CH COO- HC H O Make a couple of copies of this for class COO- CH 3 C H 2 HO H C COO- C H 2 COO- COOH C H 2 C C H H C COO- HO C COO- H COO- COOCOO- C H 2 COO- H C H 2 H C O C COO- H C O O COO- SCo. A HO C COO- C CH COO- HC H 2 HO H C COO- C H 2 COO- COOO HO H C COO- C CH COO- HC H HO H COO- C C H 2 COO- H C H H COOC H 2 COO- C H 2 C COOH COO- COOCOO- C H 2 COO- H C H 2 H C O SCo. A C C COOH COO- HO C COO- C HO C C H 2 C H COO- COOCOO- H COO- C C H 2 C H O COO- H C H 2 H C O SCo. A C C H O COO-

Biotin + CO 2 O C O-