Gluconeogenesis

Definition : Non Carbohydrate Glucose Site : Liver (80%), Kidney 20%)

? Small IntestineWhy Glucose is very important!• Brain always requires glucose• In muscle as substrate for ATP production without oxygen• Erythrocyte use only glucose for energy production• Mammary gland lactoseGluconeogenesis : For lactate clearanceIn Ruminant propionic acid is substrate for gluconeogenesis

Lactic Acid Glucose The path : TCA Cycle and reversal of glycolysiswith four additional enzymes:

Pyruvate Carboxylase PEP Carboxykinase F 1,6 BPase G 6Pase

Glycerol GlucoseGlycerol from lipolysis ( break down of Triglyceride)taken up by the liver

Glycogenic amino acids glucose

PEP

CHCH

H2CS

CH

NHC

N

O

(CH2)4 C NH R

O

CO

-OC

C

CH3

O O

O

C

CH2

C

C

O

O O

OO

CHCH

H2CS

CH

NHC

HN

O

(CH2)4 C NH R

O

carboxybiotin

pyruvate

oxaloacetate

biotin

ATP

ADP

Pi

+

HCO3-

Mg++

PEP Carboxykinase

Human, cow and guinea pig, in the mitochondria

and in the cytoplasm In rats only in the mitochondrions In birds and marmots only in the

mitochondrionMalate and PEP in human exit from the

mitochondrionIn rats malate transported out of the

mitochondrion and converted to oxaloacetate

Gluconeogenesis and Glycolysis are reciprocally regulated

• Fructose 1,6-bisphosphatase is main regulatory step in gluconeogenesis.

• Corresponding step in glycolysis is 6-phosphofructo-1-kinase (PFK-1).

• These two enzymes are regulated in a reciprocal manner by several metabolites.

Fructose-6-phosphate

Fructose 1,6-bisphosphate

6-phosphofructo-1-kinase

Fructose 1,6-bisphosphatase

+ Citrate

- AMP

- F 2,6-BP

Citrate -

AMP +

F 2,6-BP +

Reciprocal control—prevents simultaneous reactions in same cell.

Propionate Glucose

GlucogenicKetogenicBoth Glucogenic & Ketogenic

Citrate

Isocitrate

-Ketoglutarate

Succinyl CoASuccinate

Fumarate

Malate

Oxaloacetate

Glu

Gln

ArgHisPro

Asn Asp

Phosphoenol-pyruvate

Glucose

Pyruvate

Acetyl CoA Acetoacetate

LeuLysPheTrpTyr

Ile

AlaCysGlySerThrTrp

IleMetThrVal

PheTyr

Citric Acid Cycle

Fates of Amino Acid degradation products

GlucogenicKetogenicBoth Glucogenic & Ketogenic

Citrate

Isocitrate

-Ketoglutarate

Succinyl CoASuccinate

Fumarate

Malate

Oxaloacetate

Glu

Gln

ArgHisPro

Asn Asp

Phosphoenol-pyruvate

Glucose

Pyruvate

Acetyl CoA Acetoacetate

LeuLysPheTrpTyr

Ile

AlaCysGlySerThrTrp

IleMetThrVal

PheTyr

Citric Acid Cycle

Fates of Amino Acid degradation products