Gluconeogenesis Flashcards
What tissues are dependent on glucose for continuous supply of energy ?
Brain
Erythrocytes
Testes
Kidney medulla
Skeletal muscles under anaerobic conditions
Major substrate for gluconeogenesis
Propionate from odd chain FA
Proprionate: propionyl coa + acetyl-CoA
Proprionate is gluconeogenic.
Process that clears lactate produced by muscles and erythrocytes and glycerol produced by adipose tissue ?
Gluconeogenesis
Glycogen reserves last for how long before depleted and gluconeogenesis needs to occur ?
10-18 hours
Defects in gluconeogenesis can cause hypoglycemia.
Major substrates/precursors for gluconeogenesis ?
Lactate
Pyruvate
Glucogenic AA
Propionate (remaining 2 C of the FA)
Glycerol (TG)
Gluconeogenesis occurs in which part of the cell and in what organs ?
Cytosol of the cell
Liver (mainly) and approx 10% in the kidney
**During prolonged fasting, the kidneys become major glucose producing organs, contributing to approx 40% of total glucose production.
These 3 irriversible steps of glycolysis are bypassed by alternate enzymes specific to gluconeogenesis :
Hexokinase
PFK-1
Pyruvate kinase
Pyruvate converts to what in case of activation of gluconeogenesis ?
Oxaloacetate
Pyruvate to oxaloactetate catalyzed by what enzyme ?
Pyruvate carboxylase
What enzyme regulates gluconeogenesis and requires Acetyl-CoA for its activity ?
Pyruvate carboxylase
Fructose 1,6-bisphosphatase is also regulatory.
Pyruvate carboxylase depends on what to catalyze conversion of pyruvate to oxaloacetate in the presence of ATP & CO2 ?
Biotin
Biotin is a cofactor responsible for carbon dioxide transfer in several carboxylase enzymes. Raw egg whites contains avidin which binds to biotin and prevents its absorption.
2 fates of oxaloacetate ?
- substrate for gluconeogenesis
- replenish TCA cycle with oxaloacetate
Where is oxaloacetate synthesized ?
Mitochondrial matrix
It has to be transported to the cytosol to be used in gluconeogenesis where the rest of the pathway occurs. Due to impermeability of the membrane, oxaloacetate cannot diffuse and must be converted to malate and then transported to the cytosol where malate can be converted back to oxaloacetate for gluconeogenesis.
GTP used in what reaction of gluconeogenesis ?
Phosphoenolpyruvate carboxykinase
2 enzymes involved in the conversion of pyruvate to phosphoenolpyruvtate
Pyruvate carboxylase in the mitochondria (pyruvate –> oxaloacetate)
Phosphoenolpyruvate carboxykinase in the cytosol (oxaloacetate –> phosphoenolpyruvate).
**Pyruvate carboxylase is allosterically activated by :
Elevated levels of Acetyl-CoA in the mitochondria.
For instance during fasting state
Fasting –> Glucogon –> Fat breakdown –> Acetyl CoA
High amount of Acetyl CoA if someone is fasting.
Acetyl CoA is an allosteric inhibitor for:
Pyruvate dehydrogenase
You wanna go in the oxaloacetate direction, not go back and make more acetyl coa.
What enzyme is present in both mito and cytosol and responsible for reversible conversion of malate and oxaloacetate?
Malate dehydrogenase
Fructose 1,6 bisphosphatase
Fructose 1,6 bisphosphate to fructose-6-phosphate
What enzyme revereses the action of Hexokinase
Glucose 6 phosphatase
(Catalyses the conversion of glucose-6-phosphate to glucose)
Glucose is no longer traped
The presence or absence of this enzyme in a tissue determines if the tissue can contribue to maintenance of blood glucose or not.
Absent in the muscle * do not contribute to blood glucose maintenance.
Liver and kidney have this enzyme in order to release free glucose.
Glucose-6-phosphatase is located in what specific organelle?
Endoplasmic reticulum
The ATP required for gluconeogenesis is supplied by the oxidation of:
Fatty acids
Pyruvate –> oxaloacetate
Pyruvate carboxylase
Using biotin as a cofactor
Oxaloacetate –> phosphoenolpyruvate :
Phosphoenolpyruvate carboxykinase
Using GTP
