Gluconeogenesis is the process of generating glucose from non-carbohydrate precursors like lactate, pyruvate, glycerol, and amino acids. This process is required during fasting when glycogen stores have been depleted. Precursors enter the Krebs cycle and are converted to oxaloacetate, then glucose. Gluconeogenesis is regulated by insulin and glucagon to maintain blood glucose levels - insulin stimulates glucose uptake and use, while glucagon inhibits glucose use and stimulates gluconeogenesis and glycogen breakdown to increase blood sugar.
Gluconeogenesis and regulation of carbohydrate metabolism.
1. GLUCONEOGENESIS
Gluconeogenesis is the process whereby precursors
such as lactate, pyruvate, glycerol, and amino acid
are converted to glucose.
Fasting requires all the glucose to be synthesized
from these non-carbohydrate precursors.
Most precursors must enter the Krebs cycle at some
point to be converted to oxaloacetate.
Oxaloacetate is the starting material for
gluconeogenesis
2. Gluconeogenesis is:
The synthesis of
glucose from
carbon atoms of
noncarbohydrate
compounds.
Required when
glycogen stores
are depleted.
2
GLUCONEOGENESIS: GLUCOSE
SYNTHESIS
3. Carbon atoms for gluconeogenesis from lactate,
some amino acids, and glycerol are converted to
pyruvate or other intermediates.
Seven reactions are the reverse of glycolysis and
use the same enzymes.
Three reactions are not reversible.
Reaction 1 Hexokinase
Reaction 3 Phosphofructokinase
Reaction 10 Pyruvate kinase
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GLUCONEOGENESIS: GLUCOSE
SYNTHESIS
5. GLUCOSE:
OBLIGATE FUEL FOR CNS & RBC’S
CNS/Brain
Dependent on glucose as primary source of fuel
Uses ~120g glucose/day of total 160-200 g/d
RBC
Dependent on glucose
Lack mitochondria
6. REGULATION OF CARBOHYDRATE
METABOLISM
Whole carbohydrate metabolism is regulated
mainly by three hormones;
Insulin---- Stimulates glucose consuming process
to ↓ blood glucose level.
Eg: glycolysis, glycogenesis,
lipogenesis, protein synthesis
Glucagon, Epinephrine: Inhibits glucose
consuming pathways to↑blood sugar level.
Eg: gluconeogenesis, glycogenolysis, lipolysis,
ketogenesis, protein break down.
7. REGULATION OF BLOOD GLUCOSE
The normal value for glucose in whole blood
glucose is 65-100 mg/dl or 3.5 – 5.6 mmol/L
Factors Maintaining Blood Sugar:
The major factors which cause entry of glucose
into blood are:
1. absorption from intestine
2. glycogenolysis and
3. gluconeogenesis
8. The main factors leading to depletion of
glucose in blood are:
1. utilization of tissues for energy
2. glycogen synthesis and
3. conversion into fat
9. REGULATION OF BLOOD GLUCOSE LEVELS
INSULIN
Anabolic in response to hyperglycemia
Liver
Stimulates glycogen synthesis, glycolysis, and fatty acid
synthesis
Muscle
Stimulates glycogen synthesis
Adipose
Stimulates lipoprotein lipase resulting in uptake of fatty
acids from chylomicrons and VLDL
Stimulates glycolysis for glycerol phosphate synthesis
(precurser to triglycerides)
14. REGULATION OF CARBOHYDRATE
METABOLISM
Commonly used terminology:
"a" is the form of the enzyme that tends to be
active, and independent of allosteric regulators
(in the case of Glycogen Phosphorylase, when
phosphorylated).
"b" is the form of the enzyme that is dependent
on local allosteric controls (in the case of
Glycogen Phosphorylase when dephosphorylated
15.
16. The cAMP cascade induced in liver by glucagon or
epinephrine has the opposite effect on glycogen
synthesis.
Glycogen Synthase is phosphorylated by Protein
Kinase A as well as by Phosphorylase Kinase.
Phosphorylation of Glycogen Synthase promotes
the "b" (less active) conformation.
The cAMP cascade thus inhibits glycogen
synthesis.
Instead of being converted to glycogen, glucose-1-
P in liver may be converted to glucose-6-P, and
dephosphorylated for release to the blood.
