Fates of pyruvate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Learning outcomes
At the end of this lecture you should be able to:
• List the fates of pyruvate
• Describe the conversion of pyruvate to lactate
• List the glucogenic amino acids that can metabolize to form pyruvate
• Discuss the transamination of pyruvate to alanine
• Explain how the pyruvate malate cycle links glycolysis with fatty acid
metabolism
• Recognize that the conversion of pyruvate to acetyl CoA is an
irreversible process
Dr Fatahiya Kashif Carbohydrate metabolism
 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Glucose

Glucose 6P

Fructose 1,6 bisP

PEP

Pyruvate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Glucose
Glycine
Serine
Threonine
Pyruvate Oxaloacetate
Cysteine
Alanine

Acetyl CoA Malate

Ethanol

Lactate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

NADH/NAD+ ratio

Pyruvate to lactate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate to lactate
↑NADH/NAD+ ratio
Pyruvate

NADH
NADH

LACTATE DEHYDROGENASE
LACTATE DEHYDROGENASE

NAD⁺
NAD⁺

Lactate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Source of gluconeogenesis

Glucogenic amino acids

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Glucogenic amino acids

Glycine
Serine
Threonine Pyruvate
Cysteine
Alanine

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

H
H2N
O C COOH
R
ααamino
keto acid
acid
Dr Fatahiya Kashif Carbohydrate metabolism
 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Transamination

NH3

Alanine Pyruvate
PLP

NH3

ALANINE AMINOTRANSFERASE
ALANINE AMINOTRANSFERASE

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

NH2 NH2
Alanine
Pyruvate Pyruvate
Alanine
PLP
ALANINE AMINOTRANSFERASE
ALANINE AMINOTRANSFERASE

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate, malate,
oxaloacetate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate Oxaloacetate

Malate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Oxaloacetate
2H
MALATE DEHYDROGENASE
MALATE DEHYDROGENASE
NADH / NAD+

Malate

MALIC ENZYME
MALIC ENZYME
NADPH / NADP+
CO2

Pyruvate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate carboxylase
ATP BIOTIN

PYRUVATE CARBOXYLASE
PYRUVATE CARBOXYLASE

Pyruvate Oxaloacetate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

A link between glycolysis and fatty acid synthesis

Pyruvate malate cycle

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate-malate
Cytosol cycle Mitosol
Glucose acetyl CoA

NAD⁺ +
NADH + H⁺

Oxaloacetate

Intermembrane space
Malate Oxaloacetate
Malate dehydrogenase Cirate synthase
Malate dehydrogenase Cirate synthase

NADP⁺ Citrate Citrate

Citrate lyase
Citrate
ATPlyase

NADPH
acetyl CoA
Malic enzyme
Malic enzyme

FA synthesis

Pyruvate Pyruvate

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate to acetyl CoA

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Pyruvate

PYRUVATE DEHYDROGENASE COMPLEX

PYRUVATE DEHYDROGENASE COMPLEX
NADH / NAD+

FADH2 / FAD
CO2
TPP

LIPOIC ACID

CoA

Acetyl CoA

Dr Fatahiya Kashif Carbohydrate metabolism

 Glucogenic amino
Fates Lactate Transamination Pyruvate malate cycle Acetyl CoA
acids

Summary
• The different fate of pyruvate depends upon the metabolic needs of the body.
Enzymes, coenzymes and the energy status.
• In the absence of oxygen, lactate is the end product
• In extreme starvation/ or catabolic states the muscle protein is broken down into
amino acids, some of them are glucogenic and may end up in gluconeogenesis
• Transamination is a reversible interconversion of amino acids and keto acids
• Glycolysis is linked to fatty acid metabolism thru pyruvate malate cycle, which
also recycles NAD+ for glycolysis and NADPH for fatty acid synthesis
• When oxygen is abundant, pyruvate enters the mitochondria where it is
irreversibly converted to acetyl CoA which may enter the citric acid cycle or fat
metabolism

Dr Fatahiya Kashif Carbohydrate metabolism