Gluconeogenesis Flashcards
Gluconeogenesis
- occurs in the cytoplasm and mitochondria, predominantly in the liver
- anabolic pathway – requires ATP
- occurs during fasting when there is a decrease in glycogen reserves
- synthesis of glucose from noncarbohydrate precursors including pyruvate, lactate, glycerol and amino acids
- inhibited by insulin
- promoted by glucagon
What are the substrates for gluconeogenesis?
- glycerol 3-phosphate (from stored fats, triacylglycerols in adipose tissue)
- lactate (from anaerobic glycolysis)
- glucogenic amino acids (from muscle proteins)
What lowers blood sugar levels?
insulin
What raises blood sugar levels?
stimulation of gluconeogeneis and glycogenolysis by: glucagon, epinephrine, cortisol, growth hormone
Glucogenic Amino Acids
- amino acids that can be converted into intermediates that feed into gluconeogenesis
- includes all amino acids except for leucine and lysine
- catabolism of one of these AAs produce either pyruvate or one of the intermediates in the Krebs Cycle
Ketogenic Amino Acids
- amino acids that can be converted into ketone bodies that can be used as an alternative fuel especially during periods of starvation
- includes: leucine, isoleucine, tryptophan, lysine, tyrosine, phenylalanine
- catabolism of these AAs produces acetyl CoA or acetoacetyl CoA
List the enzymes in the order they occur during Gluconeogenesis (11)
- Pyruvate Carboxylase
- Phosphoenolpyruvate Carboxykinase
- Enolase
- Phosphoglycerate Mutase
- Phosphoglycerate Kinase
- Glyceraldehyde 3-Phosphate Dehydrogenase
(7. Triose Phosphate Isomerase) - Fructose Bisphosphate Aldose
- Fructose 1,6-Bisphosphatase-1 (FBPase-1)
- Phosphohexose Isomerase
- Glucose 6-Phosphatase
Pyruvate Carboxylase
- mitochondrial enzyme
- requires 1 ATP
- converts pyruvate into oxaloacetate (adds another carbon)
- activated by acetyl CoA (from beta-oxidation) and ATP
- inhibited by ADP/AMP
Oxaloacetate
- CAC intermediate
- can’t leave mitochondria so is reduced to malate that leaves mitochondria via malate-aspartate shuttle then in cytoplasm malate is oxidized back to oxaloacetate
Phosphoenolpyruvate Carboxykinase (PEPCK)
- located in cytoplasm
- converts oxaloacetate to PEP in a reaction that requires GTP
- phosphorylates oxaloacetate to form PEP
- activated by glucagon and cortisol
___ and ___ enzymes are used to avoid the action of pyruvate kinase by converting pyruvate back into PEP
pyruvate carboxylase and PEPCK
Fructose 1,6-Bisphosphatase (FBPase-1)
- located in cytoplasm
- key control point
- rate limiting step
- removes a phosphate from fructose 1,6-bisphosphate to produce Fructose 6-Phosphate
- activated by ATP
- inhibited by AMP and Fructose 2,6-Bisphosphate
How does Glucagon effect Fructose 2,6-Bisphosphate?
it lowers levels of Fructose 2,6-BP which stimulates gluconeogenesis
How does Insulin effect Fructose 2,6-Bisphosphate?
it increases levels of Fructose 2,6-BP which inhibits gluconeogenesis
Glucose 6-Phosphatase
- found in lumen of ER in liver cells
- used to avoid glucokinase and hexokinase
- converts glucose 6-phosphate into glucose (glucose can now leave cell via GLUT transporters)
- absence of this in muscles means that muscle glycogen can’t serve as a source of blood glucose
- enzyme is also used during breakdown of glycogen
