Integrative Metabolism: Significance

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1 Integrative Metabolism: Significance Energy Containing Nutrients Carbohydrates Fats Proteins Catabolism Energy Depleted End Products H 2 O NH 3 ADP + Pi NAD + NADP + FAD + Pi NADH+H + NADPH+H + FADH2 Cell Macromolecules Proteins Polysaccharides Lipids Nucleic Acids Anabolism Precursor Molecules Amino Acids Sugars Fatty Acids Nitrogenous Bases

2 Foods Proteins Carbohydrates Lipids Amino Acids GLYCOLYSIS PDH COMPLEX Pyruvate NADH NADH + H + + H + Fatty Acid & Glycerol Acetyl CoA KREBS CYCLE NADH + H + NADH 2 ETC e e e NH 3 O 2 H2 O Waste Products

3 Metabolic Profile of Organs Pancreas Secretes insulin and glucagon in response to changes in blood glucose concentration. Liver Processes fats, carbohydrates, proteins from diet; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea. Portal Vein Carries nutrients from intestine to liver. Small Intestine Absorbs nutrients from the diet, moves them into blood or lymphatic system. Brain Transports ions to maintain membrane potential; integrates inputs from the body and surroundings; sends signals to other organs. Lymphatic System Carries lipids from intestine to liver Adipose Tissue Synthesizes, stores, and mobilizes triacylglycerols. Skeletal Muscle Uses to do mechanical work.

4 Role of the Liver: Carbohydrate Metabolism Blood Cell Pentose Phosphate Cycle -6-P Fructose-6-P Glycogen Glycolysis NADP + NADPH Ribose DNA, RNA Pyruvate Acetyl-CoA Fatty Acids ETS TCA Cycle

5 Role of the Liver: Lipid Metabolism Glycerol Lipoprotein Complexes Triacylglycerol Fatty acyl-coa Acetyl-CoA FA β-oxidation Malonyl-CoA FA Synthesis Fatty Acids Acetoacetate Acetone + Ketone Bodies β-hydroxybutyrate Cholesterol Phospholipids

6 Role of the Liver: Amino Acid Metabolism Glycogen Metabolism Amino acids as precursors to synthesize plasma proteins NH 3 Carbamoyl-P Ornithine Urea Citrulline Urea Cycle Arginine Asn Aspartate Phe Tyr Ala Cys Gly Ser Thr Oxaloacetate Malate Argininosuccinate Fumarate Succinate -6-P Pyruvate Acetyl-CoA Tricarboxylic Acid Cycle Citrate Isocitrate α-ketoglutarate Succinyl CoA Ile Met Val Thr Gluconeogenesis Ketone Bodies Acetoacetate β-hydroxybutyrate Gln Glu Methylmalonyl CoA Propionyl-CoA Leu Phe Tyr Trp Lys Pro His Arg

7 Role of Skeletal Muscles DURING EXERCISE DURING STARVATION Mobilization of Glycogen Stores Glycogen -1P -6P Muscle Proteins Fatty Acids & Ketone Bodies (Provided by Liver) Catabolism Lactate Dehydrogenase Lactate Pyruvate Transamination Alanine Used as Fuels ENERGY ()

8 Role of Adipose Tissue (from the Liver) VLDL (from the Liver) Fatty Acids Glycerol 3-phosphate Fatty Acyl CoA Triacylglycerols Hormonesensitive Lipase Glycerol Fatty Acids Glycerol Fatty Acid-albumin (to the Liver) Complexes (to the Liver) Hormone-sensitive lipase key to mobilization of TG stores from adipose cells.

9 Role of Heart Muscle The activity of heart muscle is constant and rhythmic The heart functions as a completely aerobic organ and is very rich in mitochondria prefers fatty acid as fuel Continually nourished with oxygen and free fatty acid, glucose, or ketone bodies as fuel

10 Heart: Aerobic Metabolism Lactate MCT GLUT G 6-P Glycolysis Pyruvate Glycogen ADP + Pi CYTOSOL Contractile Work, S.R. Ca 2+ uptake, Ion homeostatis ADP + Pi H + O 2 PDH Acetyl-CoA NADH Electron Transport Chain ase ADP + Pi TG Citric Acid Cycle Acetyl-CoA Fatty Acid β-oxidation MITOCHONDRION CPT-I Fat Fatty Acids Heart Cells: Rich In Mitochondria Fatty Acids: Preferred Fuel Source

11 Role of the Brain Very high respiratory metabolism depends on glucose supply from the blood Starvation Ketone Bodies Normal Diet Under fasting condition, brain can use ketone bodies β-hydroxybutyrate as fuel ADP + P i Electrogenic Transport By Na + K + Atpase Active transport requires expenditure

12 Take Home Points Metabolism serves different purposes for different tissues Liver: master regulator of blood glucose homeostasis Key organ performing gluconeogenesis, fatty acid synthesis, and ketone bodies synthesis to be used by other organs for fuel Brain: uses glucose almost exclusively, except during starvation when it uses ketone bodies as fuels Skeletal muscles: use glycogen as source of energy under starvation, muscle proteins are used as fuels ketone bodies synthesized in liver also used a fuels. Under vigorous exercise, muscle produces lactate from pyruvate recycled to the liver to produce additional glucose Under starvation, alanine from skeletal muscle shuttled to liver for additional glucose production by liver Adipose tissue: serves primarily as triglyceride stores