2. FATE OF PYRUVATE OR Pyruvate Metabolism

3. Learning Objectives
To enlist the possible reactions that the pyruvate may undergo
To illustrate, how pyruvate enters into the Kreb’s Cycle
To explain the mechanism involved in the conversion of pyruvate into acetyl CoA

4. FATE OF PYRUVATE Acetyl CoA (for further metabolism)
oxidative
decarboxylation
Acetyl CoA (for further metabolism)
+2H+
Lactate (anaerobic)
Pyruvate
+NH3
Alanine (amino acid synthesis)
+CO2
Oxaloacetate (Gluconeogenesis)
Ethanol + CO2
Alcoholic
fermentation

5. Anaerobic Metabolism of Pyruvate
Problem
During glycolysis, NADH is formed from NAD+
But without O2, NADH cannot be oxidized to NAD+
If no more NAD+ is available (All NAD+ converted to NADH)
Glycolysis will stop…

6. Anaerobic Metabolism of Pyruvate
Solution
Turn NADH back to NAD+ by making lactate (lactic acid)
(oxidized)
(reduced)
(oxidized )

7. Anaerobic Metabolism of Pyruvate
ATP yield
Two ATPs (net) are produced in the anaerobic breakdown of one glucose
The 2 NADHs are used to reduce 2 pyruvate to 2 lactate
Reaction is fast and doesn’t require oxygen

8. Pyruvate Metabolism - Anaerobic
Lactate
NADH+H+ NAD+
Lactate Dehydrogenase
Lactate can be transported by blood to liver and
used in gluconeogenesis

9. Cori Cycle

10. Pyruvate metabolism Conversion to alanine and export to blood
Keto acid Amino acid
(ALT)

11. Alanine Cycle

12. Pyruvate metabolism (under aerobic conditions)
Prepares pyruvate to enter into TCA cycle
Electron Transport Chain
TCA Cycle

13. Pyruvate metabolism (under aerobic conditions)
SITE : Mitochondrion
Pyruvate dehydrogenate(PDH) Complex Consists of:
2 Molecules of PDH
8 Molecules of Flavoprotein (with dihydrolipoyl dehydrogenase)
One Molecule of dihydrolipoyl trans-acetylase

14. Pyruvate metabolism (under aerobic conditions)
Coenzymes & Cofactors Required:
TPP, Lipoic acid, CoASH, FAD, NAD+ and Mg++
Pyruvate transporter:
For transport of pyruvate from cytoplasm into mitochondrion

15. Mechanism of conversion of pyruvate into acetyl CoA
TPP
TPP

16. Summary 2 Pyruvate 2 Acetyl CoA Energetics
2 NAD
PDH complex
2 NADH + H
2CO2
2 Acetyl CoA
Energetics
2NADH + H+  6 ATP a high energy thio-ester group in the form of acetyl CoA

17. Inhibitors / Clinical aspects:
1. Arsenite / Hg++ ions bind with SH group of lipoic acid and inhibit PDH complex
2. Dietary deficiency of thiamine & chronic alcoholics  thiamine deficiency  decreased PDH activity
3. Inherited deficiency of PDH
All these conditions   pyruvate   lactate

18. Regulation

20. Mechanism of conversion of pyruvate into acetyl CoA