Carbohydrate Metabolism

Gluconeogenesis

Definition : Gluconeogenesis
Gluconeogenesis..
Gluconeogenesis (de novo synthesis of

glucose) is the synthesis of glucose from non

noncarbohydrate substrates such as:
Amino acids
Glycerol
y
Lactate & pyruvate
Propionate

Precursors of gluconeogenesis
gluconeogenesis.
During gluconeogenesis, glucose is

synthesized from:
Amino acids (glycogenic aa)
Glycerol (from TAG)
Lactate & pyruvate
Propionate (from odd chain FA)

Importance of gluconeogenesis
Some tissues,
tissues such as the brain and the

erythrocytes are completely dependant on

constant supply of glucose.
glucose
When the dietary carbohydrates are not

sufficient,, the blood glucose

g
level is
maintained by glycogenolysis in liver and also
through
g synthesis
y
of new g
glucose
(gluconeogenesis)

Site of gluconeogenesis
It primarily occurs in the liver during fasting.
It can also occur in the tubular cells of the

kidneys (contribute 10%)

Gluconeogenesis
The pathway is basically the reverse of

glycolysis.
Endergonic
E d
i process that
th t consumes ATP

Enzymes of gluconeogenesis
The irreversible reactions in glycolysis are

catalyzed by different enzymes that are

unique to gluconeogenesis

The irreversible reactions in glycolysis

gy y
are catalyzed by:

o Hexokinase.
o phosphofructokinase
o Pyruvate Kinase

The reversal of pyruvate to

phosphoenolpyruvate
The reaction of pyruvate kinase is reversed by

two separate reactions,

reactions taking place inside the
mitochondrion and the cytosol.
1.
1 pyruvate
t carboxylase
b
l
2. phosphoenol pyruvate carboxykinase

In the mitochondrial matrix

Pyruvate in the mitochondria will be converted

to oxaloacetate,, byy pyruvate

py
carboxylase.
y
Oxaloacetate is converted to malate
Malate is then transported back to the cytosol

In the cytosol
Malate is converted to oxaloacetate.
Oxaloacetate is converted to pyruvate by

phosphoenolpyruvate carboxykinase

Conversion of FF-1,6-BP to F
F--6-P

Conversion of GG-6-P to Glucose

The Cori Cycle

It is the process by which lactate produced

by muscles during strenuous anaerobic

exercise is converted back to glucose
through gluconeogenesis,
gluconeogenesis and then returned
to the peripheral tissues

The Cori Cycle

STEPS

1. Lactate produced in muscle is transported to

the liver.
liver
2. Lactate is converted to pyruvate by Lactate

Dehydrogenase
y g

The Cori Cycle

3. Pyruvate
y
is used as a substrate for

gluconeogenesis
4. Glucose is returned to the muscles through

the blood stream

Conversion of glycerol to glucose

Glycerol derived from the degradation of fats

(TAG) is converted to dihydroxyacetone

phosphate (DHAP):

Conversion of amino acids to glucose

The keto acids (carbon skeleton) of the

glyocogenic amino acids provides various

metabolic intermediated that can be used
f glucose
for
l
synthesis
th i ((gluconeogenesis)
l
i )

Pyruvate
Pyruvate

Alanine
Alanine
Glycine
Glycine
y
CCysteine
Cysteine
t i
Tryptophan
Tryptophan
Threonine
Threonine
Serine
Serine

Aspartate
Aspartate
Asparagine
Asparagine

AcetylAcetyl-CoA

Acetoacetate

Oxaloacetate
Malate

Phenylalanine
Phenylalanine
Tyrosine
Tyrosine

Isoleucine
Isoleucine
Leucine
Leucine
T
Tryptophan
t h
Tryptophan
Threonine
Threonine

Citrate

Fumarate
-Glutarate

Isoleucine
I l
Isoleucine
i
Methionine
Methionine
Valine
Valine

Phenyalanine
Phenyalanine
Tyrosine
Tyrosine
Leucine
Leucine
Lysine
Lysine

Succinyl-CoA
Copy Right
H. Kh. Atif.
2005

Glutamate
Gl t
Glutamate
t
Glutamine
Glutamine
Arginine
Arginine
Histidine
Hi tidi
Histidine
Proline
Proline

The Glucose
Glucose
Alanine Cycle
Alanine serves as a "shuttle" for pyruvate from the

muscles to the liver.

Pyruvate produced by glycolysis in muscles is

transaminated to alanine.
Alanine is transported to the liver, where it is re-

converted to pyruvate and used for

gluconeogenesis

GLUCOSE ALANINE CYCLE

Liver

Muscles
Glucose

6 ATP
Pyruvate
-Amino
acids
-Keto
acids

Alanine
Copy Right
H. Kh. Atif.

Blood
TRANSAMINATION

Alanine

Glucose
2 ATP

GLYC
COLYSIS
S

GLUCO
ONEOG
GENESIS
S

Glucose

Pyruvate
-Amino
acids
-Keto
acids

Alanine

The Regulation of Gluconeogenesis

The rate of gluconeogenesis is primarily

regulated by substrate availability.

High concentrations of lactate, glycerol, or amino

acids stimulate gluconeogenesis

Conditions associated with high

gluconeogenesis rate
Conditions that give rise to high concentrations

of the substrates of gluconeogenesis are:

Prolonged
g fasting
g & starvation
High-fat diets
Prolonged strenuous exercise