General Concepts of Metabolism PDF

General Concepts of metabolism Prof. Dr Shereen El Tarhouny  Learning Objectives By the end of this Lecture, students should be able to Describe anabolism and catabolism Outline electron transport chain (ETC) and formation of ATP Outline glucose oxidation ...

General Concepts of metabolism Prof. Dr Shereen El Tarhouny  Learning Objectives By the end of this Lecture, students should be able to Describe anabolism and catabolism Outline electron transport chain (ETC) and formation of ATP Outline glucose oxidation  Fate of absorbed sugars A. Uptake by tissues. The uptake of glucose by tissues occurs by facilitated diffusion, i.e. requires a carrier protein known as glucose transporter (GLUT). B. Utilization by tissues  B- Utilization by tissues: The liver converts fructose and galactose into glucose Oxidation 1. Major pathway: Glycolysis, followed by oxidation of pyruvate to acetyl CoA which enters the Krebs' cycle. 2. The pentose phosphate pathway (HMP). 3. The uronic acid pathway. Conversion to substances of biologic importance as ribose, fructose, galactose, glucuronic acid, aminosugars and amino acids. Storage in the form of Glycogen (Glycogenesis) Triacylglycerols (lipogenesis) Excretion in the urine: excretion by the kidney if it exceeds 180 mg/dL, called renal threshold.  A metabolic pathway has many steps – That begin with a specific molecule and end with a product – That are each catalyzed by a specific enzyme Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Reaction 2 Reaction 3 Product Starting molecule  It describes the transfer and utilization of energy in biological systems. The body uses carbohydrate, fat, & protein nutrients consumed daily to provide the necessary energy to maintain cellular activities both at rest & during exercise.  Metabolic pathways Catabolic Anabolic Breaks down complex Consume energy to build molecules into simpler complicated molecules. compounds. Anabolic steroids = to build amylase breaks complex muscle. starches into simple sugars. The building of a protein The process of cellular from amino acids. respiration.  Cellular Chemical Reactions Exergonic reactions – Release energy. Endergonic reactions – Require energy to be added. Coupled reactions – Liberation of energy in an exergonic reaction drives an endergonic reaction. Exergonic Endergonic The Breakdown of Glucose: An Exergonic Reaction  Electron Transport Chain. Energy-rich molecules, such as glucose, are metabolized by a series of oxidation reactions ,yielding CO2 and water. The metabolic intermediates of these reactions donate electrons to NAD+ and FAD to form the energy-rich reduced NADH and FADH2. NADH and FADH2 can donate a pair of electrons to a specialized set of electron carriers, collectively called the ETC.  Electron transport chain (ETC) ADP + Pi ADP + Pi ADP + Pi Substrate NAD+ FMN CoQ Cyt. b, c1 cyt. c cyt. a, a3 O2 ATP ATP ATP As electrons are passed down the ETC, they lose much of their free energy. Part of this energy can be captured and stored by the production of ATP from ADP and Pi: oxidative phosphorylation. The remainder of the free energy not trapped as ATP is used to drive additional reactions and to generate heat.  OXIDATIVE PHOSPHORYLATION Oxidative phosphorylation occurs in the mitochondria. The transfer of electrons down the ETC is energetically favored because: o NADH is a strong electron donor. o Molecular oxygen is an avid electron acceptor. The flow of electrons from NADH to oxygen does not directly result in ATP synthesis. Electrons removed from NADH and FADH are passed along a series of carriers (cytochromes) to produce ATP.  Each NADH produces 3 ATPs. Each FADH produces 2 ATPs. The chemiosmotic hypothesis explains how the free energy generated by the transport of electrons by the ETC is used to produce ATP from ADP + Pi. H+ from NADH and FADH are accepted by O2 to form water. Degradation of food stuffs (catabolism) Carbohydrates Proteins Lipids Stage I Monosaccharides Amino acids Glycerol + Fatty acids Stage III Acetyl CoA Citric acid cycle. Electron transport chain. Stage II Phosphorylation (ATP synthesis). CO2 + H2O + Free energy (ATP)  Stage I: In this stage, complex macromolecules o f carbohydrates, proteins and lipids are broken down into smaller units, such as monosaccharides, amino acids, glycerol and fatty acids. During this stage no free energy is obtained. Stage II: In this stage, the product of stage I are catabolized to form acetyl CoA or other intermediate of citric acid cycle and some free energy is obtained.   3. Stage III:  During this stage most of the free energy is obtained, acetyl CoA is oxidized by citric acid cycle to produce reduced coenzymes (NADH + H and FADH2) and CO2. Reduced coenzymes are oxidized through the respiratory chain (in presence of oxygen) to form water, during this process energy is released. Part of the energy is captured as high-energy phosphate bond (ATP) and the rest is released as heat to maintain body temperature. Active acetate Kreb’s cycle Reduced coenzymes + 2 CO2 O2 ETC Oxidized coenzymes + HO2 Energy ADP + Pi ATP Phosphorylation  Glycolysis (glyco = sugar; lysis = to break down) The glycolytic pathway is working in the cytosol of all tissues for the breakdown (oxidation) of glucose. To provide energy (in the form of ATP) and intermediates for other metabolic pathways. It can work in the presence of O2 (aerobic glycolysis), and in the absence of O2 (anaerobic glycolysis).  Aerobic glycolysis Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen. Oxygen is required to reoxidize the NADH formed during the Aerobic glycolysis, through the ETC. (producing 3ATPs)  Glucose Aerobic glycolysis AT P AT P Glucose → 2 pyruvate + 2 ATP + 2 NADH NAD NAD H H AT AT P P AT AT P P Pyruvate Pyruvate  Anaerobic glycolysis Allows the continued production of ATP in tissues that lack mitochondria (for example, red blood cells) or in cells deprived of sufficient oxygen (cotracting muscles). Pyruvate, is reduced by NADH to form lactate, this allows regeneration of oxidized NAD for further reaction in the absence of O2.  Glucose Anaerobic glycolysis AT P Glucose → 2 AT lactate + 2 P ATP NADH + H+ NADH + H+ NAD+ NAD+ AT AT P P AT AT P P Lactate Pyruvate Pyruvate Lactate  Effect of hormones on glycolysis 1. Insulin – induces synthesis of the 3 irreversible enzymes. – Dephosphorylates the enzymes through activation of protein phosphatase. 2. Glucagon – Represses the synthesis of the 3 irreversible enzymes. – Phosphorylates the enzymes mediated by cAMP activation of protein kinase.  Importance of glycolysis Energy production. oUnder aerobic conditions glucose ⎯⎯⎯→ 2 pyruvate + 8 ATP. oUnder anaerobic conditions glucose ⎯⎯⎯→ 2 lactate + 2 ATP.