FEED FAST CYCLE Lecture 15 FEED FAST CYCLE ABSORPTIVE STATE (FED STATE) • Two to four hours after ingestion of normal meal • ↑ glucose, Amino acids and TAG(incorporated with chylomicrons) • ↑ insulin - ↓ glucagon. • ↑ substrate availability - ↑ insulin/glucagon ratio → Anabolic state. Enzyme changes in absorptive state • Flow of intermediates through metabolic pathway is controlled by 4 mechanisms. 1. Availability of substrates( Minutes) 2. Allosteric regulation ( Minutes) ( At rate limiting steps) 3. Covalent modification of enzymes ( minutes to hours) Mostly dephosphoryted enzymes are Active 4. Induction repression of enzyme synthesis (hours to Days) LIVER Carbohydrate Metabolism • Net consumer of glucose retains 60% of glucose from portal system. 1. ↑ Phosphorylation of glucose Glucokinase , high km for glucose. High km is in absorptive state. 2. ↑ Glycogen synthesis ↑ glycogen synthase activity by dephosphorylation and ↑ G.6.Po4 levels 3. ↑Activity of HMP shunt 5-10. % glucose metabolized by liver G.6.Po4 -↑ NADPH use in fat synthesis 4. ↑ Glycolysis - ↑ Activity of regulated enzymes. 5. ↓ gluconeogenesis. Pyruvate carboxylase inactive due to ↓ level of acetyl CoA which is allosteric effector. FAT METABOLISM • ↑ fatty acid Synthesis • Availability of substrate( Acetyl CoA + NADPH from CHO metabolism) • Activation of Acetyl COA carboxylase by dephosphorylation and ↑ availability of Allosteric Activator (Citrate) Acetyl coA carboxylase Melonyl CoA • Rate limiting step/ inhibitor of fatty acid oxidation. ↑ TAG SYNTHESIS Aceyl CoA De novo synthesis from acetyl coA + Hydrolysis of TAG component of chylomicron remanant. Glycerol.3.Po4 (Provided by glycolytic metabolism of glucose) TAG (VLDL) Amino Acid Metabolism ↑ A.A Degradation • ↑ Amino acid level than liver can use in synthesis of proteins & other nitrogen containing compounds. • No storage for surplus A.A • Released in Blood for tissues to use in protein synthesis. OR • Deaminated & Carbon skeletons are degraded to pyruvate, acetyl coA and intermediates of TCA cycle oxidized for energy production for F A synthesis. • Limited capacity for branched chains. A.A degradation( metabolized in muscle). ↑Protein synthesis • No storage of proteins in liver. • Transient increase in the synthesis of hepatic proteins for replacement of protein degraded in previous post absorptive period. Adipose tissues Energy storage depot. • 70kg male -14 kg adipose tissue or half of muscle mass. • In obesity 70% of Body weight (entire volume of each adipocyte is occupied by a droplet of TAG). Carbohydrate Metabolism • ↑ glucose transport (GLUT-4). ↑ Insulin level. • ↑ glycolysis for Glycerol Po4 synthesis. • ↑ HMP shunt for NADPH Production. FAT METABOLISM ↑ Synthesis of Fatty Acids • From acetyl CoA is low except when refeeding after prolonged fast. • Mostly dietary fat(chylomicrons)and VLDL from Liver. ↑TAG synthesis • Fatty Acids are provided by hydrolysis of TAG of chylomicrons and VLDL. • FA released from lipoproteins by “LPL” in capillary endothelium of muscle & adipose tissues. Glycerol Po4 for TAG synthesis comes from glycolysis (No GK). ↓TAG Degradation: • ↑ insulin → dephosphorylation of hormone sensitive lipase. Resting Skeletal Muscle • Able to respond to substantial changes in demand for ATP with muscle contraction. • At rest 30% of oxygen consumption of body. • During vigorous exercise 90% of total o2 consumption. • Oxidative tissue (potential for transient periods of anaerobic glycolysis). HEART MUSCLE SKELETAL MUSCLE Continuously active Contracts intermittently Completely Aerobic Both Aerobic & Anaerobic Negligible energy stores like Considerable stores of glycogen glycogen & lipids. Major metabolic pathways in skeletal muscles during absorptive state. Carbohydrate metabolism • ↑ transport of glucose • Glycogen synthesis Fat Metabolism • F.A are of secondary importance as fuel for muscles (FED state). Only glucose is the source of energy. Amino Acid Metabolism • ↑ Protein synthesis • ↑ uptake of branched chain amino acids & degradation( branched chain α – amino acid transferase). BRAIN • 2% of adult weight/ receives 15% of cardiac output. • 20% of basal oxygen consumption at rest and consumes 25% of total Glucose. • Glucose uptake is by GLUT 3,4 • Glycogen stores are minimal so continuous supply of glucose is essential. • In hypoglycemia severe and irreversible damage can occur. .