Carbohydrates 3 Flashcards
Location of GNG
mainly in liver; after prolonged starvation kidneys can as well–only liver produces the G-6-Pase enzyme that can free glucose from the phosphate so it may enter circulation
Precursors for GNG
amino acids (mainly alanine), lactate, glycerol; all of these can readily be converted into pyruvate or OAA
4 Rxns of GNG that are needed to pass the 3 irreversible rxns of glycolysis (energy requirements if applicable)
- Pyruvate –> OAA –> PEP (pyruvate carboxylase, PEP carboxykinase; both require input of energy) (requires 2 ATP’s and 1 GTP per pyruvate so 4 ATP’s and 2 GTP’s for one molecule of glucose by GNG)
- F-1,6-BisP –> F-6-P (fructose-1,6-bisphosphatase)
- G-6-P –> Glucose (Glucose-6-Phosphatase)
Regulation of Pyruvate Carboxylase
pyruvate–> OAA; inhibited by insulin
Regulation by Fructose-1,6-Bisphosphatase
F-1,6-BisP –> F-6-P; inhibited by F-2,6-BisP and AMP
stimulated by Citrate MAIN REGULATION STEP
Regulation of PEP carboxylase
OAA–> PEP; Inhibited by insulin, AMP
Stimulated by Glucagon, cAMP
Regulation of Glucose-6-Phosphatase
G-6-P –> Glucose; inhibited by insulin
stimulated by glucagon
Insufficient GNG activity
Mutation in F-1,6-BisPase–classical symptoms of fasting hypoglycemia w/ metabolic acidosis;
also can be caused by liver disease or active alcohol metabolism
Cells w/ high levels of NADH have what problem?
holding onto pyruvate; if NADH levels are high, cell will ferment pyruvate to lactate to regenerate NAD+; GNG requires a well-function liver w/ low levels of NADH
Role of Acetyl-CoA in GNG/Glycolysis
High levels stimulate pyruvate carboxylase so GNG proceeds and inhibit PDH complex so less acetyl-CoA is made
Why is Pentose Phosphate Pathway (PPP) important? Where does it occur?
Ties together GNG and glycolysis to adjust cellular metabolism to the demands of ATP, NADH and NADPH; alternative pathway for glucose degradation; MAIN source of NADPH/riboses for biosynthesis rxns; PPP occurs in cellular cytosol
Oxidative Stage of PPP
G-6-P –> Ribose-5-Phosphate(pentose); gives off 2 NADPH molecules
Non-Oxidative Stage of PPP
reversible transketolase and transaldolase rxns; carbon pentoses are rearranged to form glycolytic intermediates
Regulated Step of PPP
G-6-P –> Phosphogluconolactone (G-6-P dehydrogenase)
Inhibited by NADPH!
Glucose-6-Phosphate Dehydrogenase Insufficiency
limits ability of PPP to generate NADPH for reduction of glutathione in RBC’s; RBC’s become sensitive to high levels of H2O2 which can cause hemolytic episodes; hemolysis occurs during infections, administration of H2O2 producing drugs, consumption of fava beans