GLUCONEOGENESIS

Gluconeogenesis

the synthesis of glucose from noncarbohydrate molecules

Noncarbohydrate:lactate, pyruvate, glycerol, and certain α-keto acids (molecules derived from amino acids).

Where occur in ?

primarily in the liver. In certain situations (i.e., metabolic acidosis or

starvation) the kidney can make new glucose. Very little in brain or muscle

The pathway

The reaction sequence in gluconeogenesis is largely the reverse of glycolysis.

three glycolytic reactions (the reactions catalyzed by hexokinase, PFK-1, and pyruvate kinase) are irreversible.

In gluconeogenesis, alternate reactions catalyzed by different enzymes are used to bypass these obstacles.

1. Synthesis of PEP( in mitochondrial matrix)

2. Conversion of fructose-l,6-bisphosphate to fructose-6-phosphate.

(in cytosol)

3. Formation of glucose from glucose-6-phosphate. (in smooth endoplasmic reticulum)

Glucose-6-phosphatase, found only in liver and kidney, catalyzes the irreversible hydrolysis of glucoses-phosphate to form glucose and Pi. Glucose is subsequently released in to the blood.

Precursors for Gluconeogenesis

pyruvate Lactate Glycogenic amino acid Glycerol Citric acid cycle intermediates

pyruvate

lactate dehydrogenase(LDH)

NADH + H+ NAD+

lactate

Lactate

Glycerol

Glycerol 3-phosphate can be oxidized in reactions catalyzed by either of two dehydrogenases; both reactions yield reduced coenzymes.

The liver contains both dehydrogenases, so both reactions can occur there.

Energy used Two pyruvate molecules are required to

synthesize one molecule of glucose.

Energy is required at the following steps.

Pyruvate carboxylase 1ATP(×2)=2ATP

PEP carboxykinase 1GTP(×2)=2ATP

Phospholglycerate kinase 1ATP(×2)=2ATP

ATP ADP

Phospholglycerate kinase

total=2+2+2=6ATP

Transport of oxaloacetata

Exit the mitochondrion

malic acid

malic acid Oxaloacetate

Oxaloacetate

Pyruvate

Pyruvate

Oxaloacetate

pyruvate carboxylase

ATP + CO2

ADP + Pi

malic acid

NADH + H+

NAD+

malic acidOxaloacetate

PEP

Phosphoenol pyruvate carboxkinase

GTP

GDP + CO2

Mt

Cytosol

malate dehydrogenase

Reciprocal regulation of glycolysis and gluconeogenesis Substrate cycle (Futile cycle)

A pair of opposing, metabolically irreversible reactions that catalyzes a cycle between two pathway intermediates. Substrate cycles provide sensitive regulatory sites.

The Cori cycle

An interorgan metabolic loop that recycles

carbon and transports energy from the liver to

the peripheral tissues. Glucose is released from

the liver and metabolized to produce ATP in

other tissues. The resulting lactate is then

returned to the liver for conversion back to

glucose by gluconeogenesis.

The Cori cycle

The significance of gluconeogenesis

1.To keep blood sugar level stable Gluconeogenesis meets the demands of the body for glucosewhen carbohydrate is not available in sufficient amount from the diet. More than 25% of glucose is supplied by gluconeogenesis.

2.To replenish liver glycogen

3.To regulate acid-base balance