4. BUILDING UP ENERGY gluconeogenesis.cori cycle.alanine cycle

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بسم الله الرحمن الرحيم Dr. Mohammad Muzaffar Mir Professor of Biochemistry College of Medicine, Al-jouf University


OBJECTIVES Define gluconeogenesis and list its steps. Explain the importance of gluconeogenesis and mention where it occurs. Describe Cori cycle and glucose-alanine cycle.

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Definition: The synthesis of glucose from non-carbohydrate compounds is known as Gluconeogenesis. The major substrates for gluconeogenesis are : lactate, pyruvate, glucogenic amino acids, propionate and glycerol Tissues: liver (80%) kidneys (20%) Sub-cellular location of enzymes pyruvate carboxylase: mitochondria glucose-6-phosphatase: Endoplasmic reticulum all other enzymes -cytoplasm

Reaction sequence:

Reaction sequence The conversion of pyruvate to glucose occurs in a series of eleven reactions. Seven of the reactions are catalyzed by enzymes that are also used in Glycolysis. The conversion of pyruvate to phosphenolpyruvate occurs in two steps catalyzed by pyruvate carboxylase and phosphenolpyruvate carboxykinase. Two specific phosphatases catalyze the hydrolysis of fructose 1,6-bisphosphate and glucose 6-phosphate.

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Bypass -1 Bypass -2 Bypass -3 Glycolysis and gluconeogenesis . Three steps are catalyzed by different enzymes in gluconeogenesis (the “bypass reactions”) and glycolysis; seven steps are catalyzed by the same enzymes in the two pathways. Cofactors have been omitted for simplicity. blue pink

Importance of gluconeogenesis:

Importance of gluconeogenesis Since glucose occupies a key position in the metabolism, its continuous supply is very essential to the body. Gluconeogenesis serves as an alternative source of glucose when supplies are low and is largely controlled by diet. A high carbohydrate meal reduces gluconeogenesis and fasting increases it. Brain and central nervous system, RBCs, testes and kidney medulla are dependent on glucose as fuel source. Human brain alone requires about 120 g of Glucose per day out of 160g needed by the entire body.

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Glucose is the only source of energy for skeletal muscle under anaerobic conditions. Under fasting conditions even for more than a day, glucose must be formed to meet the basal requirements of the body and maintain the intermediates of TCA cycle. This is essential for survival. Certain metabolites produced in the tissues accumulate in the blood [e.g. lactate , glycerol. propionate etc ]. Gluconeogenesis clears them very effectively from blood.

Cori Cycle :

Cori Cycle Definition: The cycle involving the utilization of lactate, produced by glycolysis in non-hepatic tissues (such as muscle and erythrocytes) for gluconeogenesis in liver and its reuse for energy purposes is known as Cori Cycle.

Sequence of events in Cori cycle:

Sequence of events in Cori cycle During anaerobic glycolysis in skeletal muscle [or RBC] , pyruvate is reduced to lactate by lactate dehydrogenase. Lactate crosses the plasma membrane and enters blood , reaches liver where it is oxidized to pyruvate. Pyruvate is converted to Glucose by gluconeogenesis which is then transported to muscle as an energy source and to replenish glycogen stores.

Glucose- Alanine cycle:

Definition : The Cycle involving the formation of alanine in muscle from pyruvate , its subsequent conversion to Glucose in liver and reuse of glucose by muscle as an energy source is called as Glucose- Alanine cycle . Sequence of events in Glucose- Alanine cycle Glucose oxidation produces pyruvate which can undergo transamination to alanine. This reaction is catalyzed by alanine transaminase, ALT. Additionally, during periods of fasting, skeletal muscle protein is degraded for the energy purposes thus releasing Alanine which is a major amino acid in protein. Glucose- Alanine cycle

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The alanine then enters the blood stream and is transported to the liver. Within the liver alanine is converted back to pyruvate which is used for gluconeogenesis. The newly formed glucose can then enter the blood for delivery back to the muscle. The amino group transported from the muscle to the liver in the form of alanine is converted to urea in the urea cycle and excreted.

Coordinated Regulation of Gluconeogenesis and Glycolysis is essential to avoid wastage of energy :

Coordinated Regulation of Gluconeogenesis and Glycolysis is essential to avoid wastage of energy Hormones Glucagon and Cortisol increase gluconeogenesis and decrease glycolysis Hormone Insulin increases glycolysis and decreases gluconeogenesis. Low blood glucose levels favor gluconeogenesis and high blood glucose levels favor glycolysis. High levels of amino acids and acetyl CoA promote gluconeogenesis. Alcohol inhibits gluconeogenesis

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