Gluconeogenesis and Lactic Acidosis Flashcards
Gluconeogenesis location
Mostly liver
Kidney is secondary
9 enzymes in cytosol
1 in mitochondria
1 in ER
Key enzymes of Gluconeogenesis (4)
G6Pase
FBPase-1
PEPCK
Pyruvate Carboxylase
Malate and Aspartate
Made in mitochondria
Shuttled out into cytosol
Yield OAA
PEPCK
2 OAA –> 2 PEP
GTP –> GDP
FBPase-1
F 1,6 BP –> F6P
H20 –> Pi
G6Pase
G6P –> glucose
H20 –> Pi
Lactate
Taken up by liver
Oxidized to pyruvate in cytosol by LDH
ALanine
Taken up by liveer
Transaminated by ALT to pyruvate
NADH regeneration
Ox of lactate to pyruvate
Ox of malate to OAA
Gluconeogenesis overall
2 pyruvate —-> glucose
4 steps irreversible
6 ATP equivalents used
2 NAD+ produced
Glucose transport
GLUT2 (hepatocyte)
Gradient favors production
FBPase-1 regulation
AMP (-)
F 2,6, BP (-)
Pyruvate Carboxylase regulation
Acetyl CoA (+)
Glucagon effect on Gluconeogenesis
Inc PKA –> phosphorylation of CREB –> Inc transcription of gluconeogenic enzymes
Inc PKA –> phosphorylation of PFK-2/FBPase-2 –> Dec F2,6 BP
Factors that increase Lactate production
Mitochondrial dysfx
Low cellular O2
Cancer Cells
Metformin