2. Gluconeogenesis
The process of synthesis of glucose or
glycogen from non-carbohydrate sources is
called Gluconeogenesis.
Substrates for Gluconeogenesis:
Glucogenic amino acid
Glycerol
Pyruvate
Lactate
Intermediates of TCA cycle
MCQ: Followings are the substrates for gluconeogenesis-
a) Alanine,
b) Leucine,
c) Glycerol d) Acetyl CoA e) Fatty Acid
3. 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
Reverse glycolysis,
TCA cycle,
Some special reactions like:
Cori cycle,
Glucose alanine cycle.
9. Cori Cycle
The pathway of
gluconeogenesis from
lactate.
Substrate: Lactate
Site: liver,
Background: Absence of
Glucose - 6 phosphatase
in skeletal muscle .
10. Glucose Glucose
2 Pyruvate 2 Pyruvate
2 Lactate 2 Lactate
MUSCLE LIVERBLOOD
2 ATP 6 ATP
Anaerobic
Glycolysis
Gluconeogenesis
Fig: The Cori Cycle
11. Lactate from tissue sources
of anaerobic glycolysis
(e.g-skeletal muscle) is
transferred to the liver
In liver,
Lactate is converted to
pyruvate to finally
produce glucose
Return of newly synthesized
glucose to the sources for
reutilization.
Steps
13. Biomedical Importance of
Gluconeogenesis
• 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
tissue.
14. Malate Shuttle
• Malate transporter in mito. Membrane
• malate dehydrogenase in both mito and
cytoplasm
Interlinking of
mitochondrial & Cytosolic
Pathways
• OAA produced in
mitochondria is impermeable
across the Mitochondrial
membrane
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.
15. Pyruvate is transported from the cytoplasm to the mitochondria.
In the mitochondria, pyruvate is converted to oxaloacetate by
pyruvate carboxylase
Oxaloacetate can not be transported to the cytoplasm.
Oxaloacetate is reduced in the mitochondria to malate:
Malate dehydrogenase
Oxaloacetate + NADH + H+ Malate + NAD+
Malate is transported to the cytoplasm and reoxidized back to
oxaloacetate:
Malate dehydrogenase
Malate + NAD+ Oxaloacetate + NADH + H+
16. Regulation of
Gluconeogenesis
The metabolic control of gluconeogenesis is
done by controlling the key steps and
enzymes.
Main Regulatory Hormones are:
Glucagon,
Insulin.
Effects:
Glucagon stimulates gluconeogenesis.