INTEGRATED METABOLISM in 1 page GENERALITIES: ATP generated by the oxidation of metabolic fuels in Glycolysis and Oxidative Phosphorylation NADPH

PH is the major electron donor in REDUCTIVE BIOSYNTHETIC pathways. NAD+ is the major electron acceptor in OXIDATIVE DEGRADATIVE pathways. GLUCOSE: Glucose-6-Phosphate has key metabolic branch points. Glucose-6-P <====> Glucose-1-P <====> Glycogen: Glycogenesis, Glycogenolysis Glucose-6-P ------> 6-Phosphogluconolactone (PPP Shunt) Glucose-6-P <====> Fructose-6-P <====> Pyruvate (Glycolysis) PYRUVATE: Key metabolic branch points Pyruvate <====> Oxaloacetate (Anaplerosis) ------> Glucose-6-P (Gluconeogenesis) Pyruvate <====> Lactate (Lactate Dehydrogenase, regeneration of NAD+ ) Pyruvate ------> Acetyl-CoA (Pyruvate Dehydrogenase) ACETYL-CoA: Primary branch points Acetyl-CoA ------> HMG-CoA (Sterol Biosynthesis) HMG-CoA ------> Cholesterol ------> Hormones etc. HMG-CoA ------> Ketone Bodies Acetyl-CoA ------> CO2 (Oxidative Phosphorylation) Acetyl-CoA <====> Fatty Acids (Lipogenesis, Lipolysis) FATTY ACID BIOSYNTHESIS: REGULATION Regulated Step: Acetyl-CoA Carboxylase: Acetyl-CoA ------>Malonyl-CoA INHIBITED by Palmitoyl-CoA, i.e. by its own product. STIMULATED by Citrate Citrate generally indicates lots of energy to spare, hence its time to do fat synthesis. GLYCOLYSIS: REGULATION Regulated Step: Phosphofructokinase (PFK): Fructose-6-Phosphate ------> Fructose-1,6-Biphosphate STIMULATED BY -- these two indicate a deficiency of energy --- Fructose-2,6-Biphosphate and AMP INHIBITED BY -- once again... Citrate and ATP GLUCONEOGENESIS: REGULATION Regulated Step: Fructose-1,6-Biphosphotase: Fructose-1,6-Biphosphate ------> Fructose-1-Phosphate INHIBITED BY AMP and Fructose-2,6,-Biphosphate (not enough energy is around for gluconeogenesis) STIMULATED BY Citrate and ATP HEXOSE MONOPHOSPHATE SHUNT: REGULATION Regulated Step: Glucose-6-Phosphate Dehydrogenase: Glucose-6-Phosphate -----> 6-Phosphogluconolactone -----> 6Phosphogluconate INHIBITED by NADPH STIMULATED by NADP+, which means we need to make more NADPH. G6PD deficiency no HMPS - cannot reduce GSSG to GSH, so RBCs lyse because of O ----> haemolytic anaemia THE HORMONES: GLUCAGON = generally catabolic o PROMOTE Gluconeogenesis in liver, glycogenolysis, lipolysis o INHIBIT Glycogenesis, Lipogenesis ADRENALINE = generally catabolic -- the "hormone of starvation" o STIMULATES Lipolysis in particular, plus the other catabolic processes o STIMULATES the release of glucagon from the pancreas CORTISOL = both catabolic and anabolic o PROMOTE Glycogenesis, Gluconeogenesis, and Proteolysis. INSULIN = generally anabolic o PROMOTE Glucose absorption by cells, amino acid transport into cells, Glycogenesis, Lipogenesis o It does NOT promote Glucose-uptake, per se, in the brain, where glucose is essential at all time anyway. o INHIBITS Gluconeogenesis and Glycogenolysis