Dr. Waheeda Nargis
Dept. of Biochemistry, UAMCH
The process of synthesis of glucose or
glycogen from non-carbohydrate sources is
Substrates for Gluconeogenesis:
Glucogenic amino acid
Intermediates of TCA cycle
MCQ: Followings are the substrates for gluconeogenesis-
c) Glycerol d) Acetyl CoA e) Fatty Acid
Features of Gluconeogenesis
Site: Liver (90%) , Kidney(10%),Intestinal epithelial cells (negligible)
On overnight fasting 90% site is Liver
& the rest in Kidney.
On prolonged fasting 60% site is Kidney
& the rest in liver
Compartment: Cytoplasm (mitochondria also participates)
Nature: Anabolic; 6 ATP needed for synthesis of one glucose from
2 pyruvate or lactate.
Pathways involved in gluconeogenesis
Some special reactions like:
Glucose alanine cycle.
Gluconeogenesis from glycerol
The initial phosphorylation of glycerol takes place at
liver rather than adipocytes since they lack the enzyme
glycerol kinase. (The shortest pathway)
Glyceraldehyde -3 phosphateReverse glycolysis
DHA-P : Dihydroxyacetone phosphate
The pathway of
Background: Absence of
Glucose - 6 phosphatase
in skeletal muscle .
2 Pyruvate 2 Pyruvate
2 Lactate 2 Lactate
2 ATP 6 ATP
Fig: The Cori Cycle
Lactate from tissue sources
of anaerobic glycolysis
(e.g-skeletal muscle) is
transferred to the liver
Lactate is converted to
pyruvate to finally
Return of newly synthesized
glucose to the sources for
Biomedical Importance of
• To maintain the blood glucose concentration
during prolonged fasting or starvation when
sufficient carbohydrate is not available from
the diet or glycogen reserves.
• It maintains the level of intermediates of the
TCA cycle even when fatty acids are the main
source of acetyl coA in the tissues.
• It clears the lactate produced by muscle and
erythrocytes and glycerol produced by adipose
• Malate transporter in mito. Membrane
• malate dehydrogenase in both mito and
mitochondrial & Cytosolic
• OAA produced in
mitochondria is impermeable
across the Mitochondrial
Thus , OAA must be converted into
malate or asparate, exported from the
mitochondrion, and converted back
into oxaloacetate in order to allow
gluconeogenesis to continue.
Pyruvate is transported from the cytoplasm to the mitochondria.
In the mitochondria, pyruvate is converted to oxaloacetate by
Oxaloacetate can not be transported to the cytoplasm.
Oxaloacetate is reduced in the mitochondria to malate:
Oxaloacetate + NADH + H+ Malate + NAD+
Malate is transported to the cytoplasm and reoxidized back to
Malate + NAD+ Oxaloacetate + NADH + H+
The metabolic control of gluconeogenesis is
done by controlling the key steps and
Main Regulatory Hormones are:
Glucagon stimulates gluconeogenesis.