Gluconeogenesis Flashcards
Gluconeogenesis
- important to maintain blood glucose levels during fasting or starvation
- LIVER!!!: synthesis of new glucose from non-carb precursors
Can mammals convert FA to sugars?
WE CANNOT MAKE GLUCOSE FROM FA!
Gluconeogenesis requires:
- source of energy
- source of carbons for the backbone of glucose
Carbon skeletons are provided for gluconeogenesis from 3 sources:
- lactate: produced in tissues such as RBCs and exercising muslces
- glucogenic amino acids: (i.e. alanine) derived from muscle protein
- glycerol: released from TAGs during lipolysis in adipose tissue GLYCEROL BACKBONE NOT FA CHAINS!
Energy for gluconeogenesis is provided by
metabolism of FA released from adipose tissue
2 ketogenic AA that can’t undergo Gluconeogenesis
Leucine and Lysine
Where is gluconeogenesis done
mostly in the LIVER, a little in the kidney
NOT IN THE MUSCLE!
Metabolism in the Cytosol
- glycolysis
- pentose phosphate pathway
- fatty acid synthesis
Metabolism in the Mitochondrial Matrix
- TCA Cycle
- oxidative phosphorylation
- B-oxidation of FA
- ketone body formation
Metabolism in BOTH the cytosol and mitochondrial matrix
- gluconeogenesis
- urea synthesis
Gluconeogenesis vs. Glycolysis
Glycolysis: occurs in all tissues, esp the muscle and brain
Gluconeogenesis: occurs mainly in the liver and a little in the kidney
** [substrate] determines directionality **
Gluconeogenesis donors
lactate (-> pyruvate)
alanine (-> pyruvate)
glycerol backbone (-> dihydroxyacetone)
3 regulated steps of glycolysis
- Hexokinase/Glucokinase
- PFK I
- Pyruvate kinase
- all require ATP
must be BYPASSED in gluconeogenesis
Bypass of Pyruvate Kinase
- Pyruvate carboxylase (mitochondria)
- Phosphoenol pyruvate carboxykinase (PEPCK) (cytoplasm and mitochondria)
ENERGY REQUIRING
- add a C then remove a C to drive unfavorable reactions forward
Bypass of PFK-I
Fructose 1,6-bisphosphatase-1 (cytoplasm)
Bypass of Hexokinase/Glucokinase
Glucose 6-phosphatase (ER)
Carboxylases ABC
ATP
Biotin
CO2
Pyruvate Carboxylase; Pyruvate Carboxykinase (PEPCK)
Pyruvate -> OAA
- either converted in mitochondria to PEP, or transferred out of mitochondria to cytosol via malate shuttle which is then converted to OAA and PEP
WHICH PATHWAY IS DEPENDENT ON NADH LEVELS
- if lactate is precursor, NADH is present in cytosol so OAA-> PEP in mitochondria
- if pyruvate is precursor, NADH has to be moved to cytosol via shuttle
Malate Shuttle
pyruvate -> OAA -> malate -> OAA -> PEP
uses and produces NADH
- without shuttle, cytosolic NADH concentrations would become limiting
PEPCK regulation
Glucagon increases transcription of the gene for PEPCK during fasting
- uses CRE and CREB
