L12: Gluneogenesis Flashcards
where does gluconeogenesis occur?
- in mitochondrion and cytoplasm
- generally occurs in the liver under fasting conditions
why use gluconeogenesis?
- glucose levels needs to be maintained since the brain uses glucose for fuel
- mostly used by brain, muscle, and red blood cells
Noncarbohydrate precursors that generate pyruvate
- lactate
- amino acids
- glycerol - breakdown of fat
fed state:
- dietary glucose is exhausted quickly
- just after a meal, the glucose you consumed is depleted after a few hours
fasting state
- breakdown of glycogen to glucose
- lactate, amino acids, and glycerol will come in and help generate glucose
- when you need a boost of energy
- goes away after about a day
starved state
- gluconeogenesis provides a relatively constant level of glucose
- provided by the liver
where does glycerol come from?
- released from fat stores (adipose cells) due to triglyceride breakdown
where does propionate come from?
- odd-chain fatty acids
- produce propiony-CoA
propionyl-CoA track
- propionyl CoA -> succinyl CoA -> TCA cycle -> oxaloacetate
which is the major gluconeogenic amino acid?
- alanine
lactate comes from?
- muscle tissues undergoing anaerobic glycolysis
- through circulation and enters liver
lactate to pyruvate
- requires lactate dehydrogenase
- requires NAD+
When NADH levels are high?
- reaction goes toward lactate
- inhibits gluconeogenesis
alanine to pyruvate
- via alanine aminotransferase
glycerol to DHAP
- glycerol -> glycerol-3-phosphate by glycerol kinase
- glycerol-3-phosphate -> DHAP by glycerol-3-phosphate dehydrogenase
unique reaction 1 of gluconeogenesis
- pyruvate -> oxaloacetate
- via pyruvate carboxylase and ATP
- also requires biotin and CO2
- reaction occurs in the membrane
oxaloacetate transport
- oxaloacetate is converted to malate and exits mitochondria
- cannot cross mitochondrial membrane on its own
- malate is transported to cytoplasm
- malate is converted back to oxaloacetate
oxaloacetate phosphorylation
- oxaloacetate -> phosphoenolpyruvate
- via phosphoenolpyruvatecarboxykinase
- requires GTP
how to form fructose-6-phosphate from fructose-1,6-bisphosphate
- uses fructose-1,6-bisphosphatase
form glucose from glucose-6-phosphate
- uses glucose-6-phosphatase
- found in liver and kidney to transport to other tissues
- occurs in the ER
- glucose-6-phosphate transported into ER lumen
- glucose transported back to the cytoplasm
which is the most preferred end product?
- glucose-6-phosphate
- because it cannot be transported out of the cell like glucose
how much energy is required for gluconeogenesis?
- 4 ATP
- 2 GTP
- 2 NADH
when is glycolysis favored?
- when energy is needed
- glycolytic intermediates are needed for biosynthesis
when is gluconeogenesis favored?
- when energy is abundant
- when glucose precursors are abundant
pyruvate carboxylase regulation
- pyruvate -> oxaloacetate
- stimulated by acetyl CoA
- inhibited by ADP
phosphoenolpyruvate carboxykinase regulation
- oxaloacetate -> phosphoenolpyruvate
- inhibited by ADP
pyruvate dehydrogenase inhibited by
- acetyl CoA
- NADH
pyruvate dehydrogenase stimulated by
- ADP
pyruvate kinase inhibited by
- PEP - pyruvate
- ATP
- Alanine
- glucagon signaling
fructose-1,6-bisphosphatase regulation
- activated by citrate
- inhibited by AMP and F-2,6-BP
PFK-1 regulation
- inhibited by ATP, citrate, and H+
- activated by F-2,6-BP and AMP
If F-2,6-BP levels are high
- indicates high glucose levels
- you want to break down glucose
low glucose results in
- release of glucagon
glucagon stimulates
- cAMP cascade
- activates PKA
PKA role in gluconeogenesis
- phosphorylation PFK2 Kinase domain
- activation of PBPase2
PBPase role
- reduces F-2,6-BP levels and increase levels of F-6-P
- No PFK stimulation
glucagon signaling also does what
- increases transcription of genes that encode enzymes that carry out gluconeogenesis
- inhibits expression of glycolytic enzyme genes
when glucose is high
- insulin activates phosphoprotein phosphatase
- removes phosphate from and activates PFK2
- increases F-2,6-BP from F-6-P
- stimulates PFK
- glycolysis predominates
glucokinase
- same role as hexokinase (present in all other body tissues)
- only in the liver
- high Km
