Gluconeogenesis Flashcards
Gluconeogenesis Definition
new synthesis of glucose
2 types of gluconeogenesis
1) Anabolic
- synthesis from non carbohydrate precursors
2) Coversion
- synthesis from other carbohydrates (C5 and C6 carbs)
Location of Gluconeogenesis
Liver and Kidney
- during overnight fast, gluconeogenesis occurs in liver (90%) and kidneys (10%)
- during prolonged fast, the kidneys take over larger percentage of gluconeogenesis (up to 40%)
Glucose requirements per day in humans
Human adult 160g of Glucose/24 hours
-120g used by the brain
Glycogen storage=190g of glucose
-once glycogen stores are depleted, glucose is produced by gluconeogenesis
Potential Substrates for Gluconeogenesis
1) Lactate
2) Pyruvate
3) Glycerol-from catabolism of triacylglycerols (Fat)
- animals do not convert fatty acids to glucose
4) alpha-ketoacids- from catabolism of glucogenic amino acids
TOP 3 have 3 carbons
Gluconeogenesis: Glycerol
- source
- reaction
Source of glycerol:
- hydrolysis of triacylglycerols in adipose tissues to form glycerol and travels to liver via blood since
- adipose tissues lack the enzyme GLYCEROL KINASE
Reaction:
1) Glycerol is converted to glycerol phosphate by Glycerol kinase at the expense of ATP-> ADP
2) Glycerol Phosphate is converted to Dihydroxyacetone phosphate by Glycerol Phosphate dehydrogenase using the coenzyme NAD+
Gluconeogenesis: Lactate
THE CORI CYCLE:
- lactate is formed during strenuous exercise in skeletal muscle and tissue lacking mitochondria
- lactate diffuses into the blood and is carried to the liver
- lactate diffuses into the liver where it is used to synthesize glucose
- glycolysis continues
Gluconeogenesis: Amino acids
Source of Amino acids:
- during fasting, amino acids come from hydrolysis of tissue proteins
- Glucose is synthesized from glucogenic amino acids
Gluconeogenesis: Pyruvate
Pyruvate is carboxylated to Oxaloacetate
-ONLY IN LIVER AND KIDNEY
1) Pyruvate (C3) converted to Oxaloacetate (C4) by pyruvate carboxylase (adds CO2) at the expense of ATP-> ADP
2) Oxaloacetate is unable to leave the mitochondria so it is reduced to malate by the enzyme Malate dehydrogenase; NADH->NAD+
3) Malate is transported across mitochondrial membrane and is reoxidizes to oxaloacetate by malate dehydrogenase linked to NAD+->NADH found in cytosol of cytoplasm
4) Oxaloacetate is simultaneously decarboxylated and phosphorylated by phosphoenolpyruvate carboxy kinase in the cytosol to form PEP
Pyruvate Carboxylase
-general info
Produces Oxaloacetate for gluconeogenesis and to replenish oxaloacetate as intermediate in T.C.A
Found in:
- kidney and liver cells
- Muscle cells which are only used to replenish oxaloacetate as intermediate in T.C.A
Biotin is prosthetic group which is attached to the R group of Lysine
Allosterically stimulated by Acetyl CoA
Biotin
Prosthetic group
- covalently attached to R group of Lysine by amide bond
- called biocytin when attached to lysine
Function:
-carries activated CO2 for carboxylation and carboxyl transfer in certain enzymes in certain enzymes gluconeogenesis and fatty acid synthesis
Vitamin: Biotin
deficiency-rash about the eyebrow, fatigue (rare), Muscle pain
PEP carboxykinase
found in the cytosol
-decarboxylates and phosphorylates oxaloacetate to PEP
Fructose 1,6-Bisphosphate -> Fructose 6-Phosphate
ONLY IN LIVER AND KIDNEYS
-catalyze by the fructose 1,6-bisphosphatase which removes orthophosphate (Pi)
REGULATED BY ENERGY CHARGE
- Low energy charge- inhibited by AMP
- inhibited by Fructose 2,6 Bisphosphate
Glucose 6-Phospahte-> Glucose
ONLY IN LIVER AND KIDNEYS
-muscles lack glucose 6-phosphate
1) Glucose 6-Phosphate in the cytoplasm is transported to the Endoplasmic Reticulum by Glucose 6-Phosphate translocase
2) Glucose 6-Phosphate in the ER is converted to Glucose by Glucose 6-Phosphatase
- loses orthophosphate
Synthesis/Degradation of Fructose 2,6-Bisphosphate
- Enzyme
- characteristics of enzyme
Fructose 2,6-BP –> Fructose 6-Phosphate
Enzymes:
Phosphofructokinase 2 (PFK2)-formes F 2,6 BP
Fructose 2,6-Bisphosphatase (FBPase2)-forms F 6-P
-FBPase2 and PFK2 reside on same polypeptide chain called the bifunctional enzyme
-Regulation is done by phosphorylation serine in the regulatory domain
-Phosphorylation turns ON the phosphatase activity (FBPase2) which reduces F 2,6BP concentration
-Dephosphorylation turns ON the kinase activity (PFK2) which increases F 2,6BP concentration
