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BIOMOLECULES AND METABOLISM 3. Metabolism and Its Control Prof. K. M. Chan Dept. of Biochemistry Chinese University Rm 513B, Basic Medical Sciences Building Tel: 3163-4420; Email: kingchan@cuhk.edu.hkBCH 1002 Biochemical Aspects of Health and Disease

BIOMOLECULES AND METABOLISM 3. Metabolism and Its Control Prof. K. M. Chan Dept. of Biochemistry Chinese University Rm 513B, Basic Medical Sciences Building Tel: 3163-4420; Email: kingchan@cuhk.edu.hk

BCH 1002 Biochemical Aspects of Health and Disease

Contents

Anabolism, catabolism, reducing power and energy production Enzyme actions Glycolysis & Krebs cycle B oxidation and fat metabolism Regulation of metabolism by hormones

3.1 Aabolism, catabolism, reducing power and energy (ATP) production

Living processes are complex of anabolic (biosynthesis) and catabolic (disintegration) reaction pathways that use carbohydrates, lipids, and proteins as energy sources and biosynthetic precursors. The processes are precisely regulated by the following ways. Compartmentation: different organs have different functions, and different pathways take place in various organelles in the cells. Each step in the pathways requires specific enzyme, co-factors and optimal pH (buffered) amd is tightly controlled by various factors.

3.1.1 Catabolism has three stages

Nutrient molecules (proteins, polysaccharides and fats from food) are hydrolyzed to their building block units by digestions. Building block units are converted to easily oxidized forms (primarily acetyl CoA). Acetyl CoA is completely oxidized to form CO2 and H2O. Energy is captured when ATP synthesis is linked to the electron transport pathway using ATP synthase.

Catabolism processes

FOOD Proteins Carbohydrates Fats Amino acids Fatty acids and glycerol Glucose Glycolysis Pyruvate Acetyl CoA Krebs (Citric acid) cycle Oxidative phosphorylation

3.1.2 Anabolism

http://www.accessexcellence.org/RC/VL/GG/ecb/ATP_ADP.html Large complex molecules are synthesized from smaller precursors. Building block molecules (amino acids, sugars and fatty acids) are produced or acquired from the diet. Because anabolic processes include the synthesis of polysaccharides and proteins from sugars and amino acids, the biosynthetic pathways increase order and complexity, they require inputs of free energy (ATP and NADPH).

3.1.3. ATP energy and Acetyl Coenzyme A (acetyl CoA)

Coenzyme A – S – C = O CH3 ATP plays an extraordinary role within cells: currency or input of energy. Hydrolysis of ATP provides an immediate and direct input of free energy to drive a variety of endergonic (energy requiring) biochemical reactions. Chemical coupling allows the cell to get the energy produced by catabolism. Thioester is also important in energy harvesting pathways for breakdown of molecules. Acetyl CoA carries one acetyl group for further catabolism of carbohydrates.

3.1.4 Reducing power

NAD+ + H+ + 2 e- NADH FAD + 2H+ + 2 e- FADH2 Cu+ + Fe3+ Cu2+ + Fe2+ ½ O2 2 e- Both energy capturing and releasing processes consist largely of redox reactions. Electron donor (reducing agent) Electron acceptor (oxidizing agent)

http://www.estrellamountain.edu/faculty/farabee/biobk/BioBookEnzym.html NAD: Nicotinamide Adenine Dinucleotide http://en.wikipedia.org/wiki/Image:NADplus.png

3.1.5 Division of labor in our body

Liver for metabolism; stomach and duodenum for digestion. Intestine for absorption. Circulation for transport (water distribution between plasma and interstitial fluid compartments). Renal system for excretion (control of body fluid and electrolyte balance) Muscle plays an important part to burn the energy from food when fed or from fat when starved. Importance of nutrients, exercise and sport (control of body composition and energy expenditure). The best way to keep your body in good shape is to do exercise.

3.2 Enzymatic Control of Metabolism

http://www.estrellamountain.edu/faculty/farabee/biobk/BioBookEnzym.html

Interconversion of the macronutrients

Protein, carbohydrate and fat are energy producing macronutrients Pathways are regulated at the following levels: certain regulatory enzymes by substrate availability, allosteric mechanisms, and covalent modification such as phosphorylation.

3.3 Carbohydrate metabolism and energy production

Glycolysis (in cytoplasm) Krebs cycle (in matrix inside mitochondria) Aerobic and anaerobic metabolism Gluconeogenesis

3.3.1 GLYCOLYSIS

Glucose can also be available from food intake. Glucose is also stored as glycogen (glycogenesis). After gluconeogenesis, glucose is converted from glycogen in liver or muscle for glycolysis. Glycolysis is the break down of a 6 C glucose sugar to two 3C pyruvate.

Central role of liver in metabolism

Glucose entering the hepatocyte is phosphorylated by glucokinase to glucose-6-phosphate (G-6-P). Other monosaccharides are also made to G-6-P via gluconeogenesis, then glucose can be stored as glycogen. When we need energy, glycolysis converts G-6-P to pyruvate and acetyl coA to enter Citric acid cycle to produce ATP energy via oxidative phosporylation (aerobic metabolism).

Glycolysis: break down of glucose in cytoplasm

Glucose-6-phosphate Glucose-1-phosphate UDP-glucose Glycogen Glucose Hexokinase Fructose-6-phosphate Fructose-1, 6-biphosphate Glyceraldehyde-3-phosphate Dihydroxyacetone phosphate (DHAP) Glycerol Glyceraldehyde-1, 3-bisphosphate Glycerate-3-phosphate Glycerate-2-phosphate Phospho-enol-pyruvate NAD + Pi NADH + H+ ATP ATP ADP ADP H2O H2O Pyruvate Lactate Lactate Dehydrogenase ATP ADP ATP ADP ATP ADP

http://www.accessexcellence.org/RC/VL/GG/ecb/outline_glycolysis.html

Pyruvate is transported across the inner mitochondrial membrane and oxidized within the matrix to acetyl CoA via TCA (Krebs) cycle. Acetyl Co A can also be produced fromβoxidation of fatty acids in the mitochondria. From which the NADH produced in the mitochondria is used for oxidative phosphorylation in the inner membrane of mitochondria to make ATP energy using water and oxygen.

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BIOMOLECULES AND METABOLISM 3. Metabolism and Its Control Prof. K. M. Chan Dept. of Biochemistry Chinese University Rm 513B, Basic Medical Sciences Building Tel: 3163-4420; Email: kingchan@cuhk.edu.hkBCH 1002 Biochemical Aspects of Health and Disease
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