FEED FAST CYCLE

Lecture 15

FEED FAST CYCLE ABSORPTIVE STATE (FED STATE)

• Two to four hours after ingestion of normal meal • ↑ , 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 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 + 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.