Download Glycolysis 4

FATE OF PYRUVATE
OR
Pyruvate Metabolism
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
FATE OF PYRUVATE
oxidative
decarboxylation
Acetyl CoA (for further metabolism)
Pyruvate
+2H+
Lactate (anaerobic)
+NH3
Alanine (amino acid synthesis)
+CO2
Oxaloacetate (Gluconeogenesis)
Alcoholic
fermentation
Ethanol + CO2
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…
Anaerobic Metabolism of Pyruvate

Solution
 Turn NADH back to NAD+ by making lactate (lactic acid)
(reduced)
NADH + H+
(oxidized )
NAD+
COO–
C
O
CH3
Pyruvate
(oxidized)
COO–
Lactate dehydrogenase
HC
OH
CH3
Lactate
(reduced)
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
Pyruvate Metabolism - Anaerobic
Lactate Dehydrogenase
Pyruvate
Lactate
NADH+H+
NAD+
• Lactate can be transported by blood to liver and
used in gluconeogenesis
Cori Cycle
Pyruvate metabolism

Conversion to alanine and export to blood
Glutamate
-Ketoglutarate
COO–
C
COO–
O
CH3
HC
Alanine amino transferase
(AAT)
(ALT)
NH3+
CH3
Pyruvate
Alanine
Keto acid
Amino acid
Alanine Cycle
Pyruvate metabolism
(under aerobic conditions)

Prepares pyruvate to enter into TCA cycle
Electron
Transport
Chain
TCA Cycle
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
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
Mechanism of conversion of pyruvate into acetyl CoA
TPP
TPP
2 Pyruvate
Summary
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
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
Regulation
Mechanism of conversion of pyruvate
into acetyl CoA