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

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Gluconeogenesis is: The synthesis of

glucose from carbon atoms of noncarbohydrate compounds.

Required when glycogen stores are depleted.

GLUCONEOGENESIS: GLUCOSE SYNTHESIS

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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 PhosphofructokinaseReaction 10 Pyruvate kinase

GLUCONEOGENESIS: GLUCOSE SYNTHESIS

REGULATION OF CARBOHYDRATE METABOLISM

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

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.

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

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

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)

ROLE IN INSULIN IN LOWERING BLOOD GLUCOSE

REGULATION OF BLOOD GLUCOSE LEVELSGLUCAGON

Catabolic, in response to hypoglycemia Liver

Activates glycogen degradation, gluconeogenesis Adipose

Stimulates lipolysis and release of fatty acids

ROLE OF GLUCAGON IN INCREASING BLOOD GLUCOSE LEVELS

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

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.