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

2. 1899-1986 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"

5. The core of the complex consists of 60 copies of E 2. At the periphery of the complex are:  30 copies of E 1 (itself a tetramer with subunits  2  2 )  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

6. 3.+ CoA-SHCoA-S - C –CH 3 O Acetyl CoA E 2 + O S – C –CH 3 SH E2E2 E2E2 4. E2E2 SH + E2E2 S S + FAD E 3 - FADH 2 E 3 - 5. FADH 2 E 3 - + NAD FAD E 3 - NADH + H + + Pyruvate dehydrogenase H 3 C-C-COO- O + TPPTPP-CH OH CH 3 + CO 2 E 1 1. + H+H+ 2. TPP-CH OH CH 3 + O S – C –CH 3 SH E2E2 E2E2 S S + H +

7. Regulation of PDH:  AcCoA (competes with CoA for E2), NADH (competes with NAD for E3) 1. Inhibited by AcCoA and NADH E2 is associated with PDH kinase and PDH phosphatase which act on E1  Phosphorylation controled by NADH/NAD, AcCoA/CoA and ATP/ADP. Increasing these ratios promotes phosphorylation and hence decreases activity. THEREFORE: Phosphorylation of E1 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. 2. Regulated by phosphorylation  phosphorylation of the E1 subunit inhibits  dephosphorylation activates.  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.

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

9. or GTP

10. H C COO- COO- C H 2 COO- C H HO C H 2 H C H C O COO- C H 2 H C H C O COO- SCoA C H 2 COO- H C C H COO- HO CH HC H COO- O C C H COO- C O CH 3 SCoA HO C COO- COO- C H 2 COO- C H 2 H C COO- COO- C H 2 COO- C H HO C H 2 H C H C O COO- C H 2 H C H C O COO- SCoA C H 2 COO- H C C H COO- HO CH HC H COO- O C C H COO- HO C COO- COO- C H 2 COO- C H 2 H C COO- COO- C H 2 COO- C H HO C H 2 H C H C O COO- C H 2 H C H C O COO- SCoA C H 2 COO- H C C H COO- HO CH HC H COO- O C C H COO- HO C COO- COO- C H 2 COO- C H 2 Make a couple of copies of this for class

11. C O O- + CO 2 Biotin