Cell Metabolism, Bioenergetics & Energy Balance PDF

Metabolism-Session 2 Cell Metabolism, Bioenergetics & energy balance Dr. Hishyar A. Najeeb MSc in Clinical Biochemistry, PhD in Cancer Studies & Molecular Medicine (Leicester Uni/UK) 0 learning outcomes 1. Define cell metabolism and explain its functions. 2. Describe the origins fates of cell nu...

Metabolism-Session 2 Cell Metabolism, Bioenergetics & energy balance Dr. Hishyar A. Najeeb MSc in Clinical Biochemistry, PhD in Cancer Studies & Molecular Medicine (Leicester Uni/UK) 0 learning outcomes 1. Define cell metabolism and explain its functions. 2. Describe the origins fates of cell nutrients. 3. Describe the relationship between catabolism and anabolism. 4. Explain the roles of redox reactions and H--carrier molecules in metabolism 5. Explain the roles of high and low energy signals in the regulation of metabolism. 6. Explain why cells need a continuous supply of energy. 7. Explain the biological roles of ATP, creatine phosphate and other molecules containing high energy of hydrolysis phosphate groups. 0 Cell metabolism 0 Cell nutrients ➢Blood contains nutrients; important to maintain normal cellular function ➢ Others substances are waste products produced by cells ➢Clinicians measure some of these substances for the diagnosis of metabolic diseases and in monitoring patient treatment. Lo1 0 Changes of blood substances do occur under a variety of situations Physiological changes ➢fasting, ➢starvation, ➢exercise, ➢pregnancy and stress. Pathological changes ➢Diabetes, ➢atherosclerosis, ➢obesity, shock, ➢malnutrition ➢certain enzyme deficiency states. Lo1 0 &MetabolismModule2018-2019.pdf-AdobeAcrobatReaderDC FileEditViewWindowHelp Clinically important cell nutrients 6 and waste products Home Tools SignIn MetabolismModul... Q 31/218 [hiShare _ExportPDF Clinicallyimportantcellnutrientsandwasteproducts Nutrient/wasteproduct mmol/L Glucose 90 Aminoacids 3 40 Triacylglycerols 2 150 Cholesterol 5 0.5 200 30 Lacticacid <1.0 TotalCO,(MostlyHCO;) 27 Urea NH, Lo1 5 52EditPDF mig/dL 5 Fattyacids 19CreatePDF Normalfastingplasmaconcentration Comment 49CombineFiles EOrganizePagesv 1Redact •Protect 30 4OptimizePDF 25uM GeFill&Sign xlAdobeSign 0 ConvertandeditPDFs withAcrobatProDC StartFreeTrial EN 10:07р 1/14/2019 Origins and fates of cell nutrients Cell nutrients circulating in the blood come from a variety of sources: ➢The diet ➢Synthesis ➢Released Lo2 from storage in the body tissues 0 With in body tissues where they undergo various chemical transformations (metabolism) including: Degradation to release energy-all tissues. Synthesis of cell components- all tissues except mature erythrocytes. ➢ ➢ Storage-liver, adipose tissue, skeletal muscle. Interconversion to other nutrients liver, adipose tissue, kidney cortex. Excretion-liver, kidney, lungs. ➢ ➢ ➢ Lo2 0 Functions of cell metabolism Cells metabolize nutrients to provide: ➢Energy ➢Building block molecules for growth, maintenance, repair and division of the cell. ➢Organic precursor molecules sucha as acetyl-CoA ➢Biosynthetic reducing power in the synthesis of cell components (NADPH). Lo2 0 Lo2 0 Catabolism and Anabolism Cell metabolism consists of pathways : ➢Catabolism ➢Anabolism ➢Catabolic pathways are oxidative, release large amounts of free energy ➢In contrast, anabolic pathways are usually reductive and use the intermediary metabolites and energy (ATP) produced by catabolism to drive the synthesis of important cell components. Lo3 0 Biological oxidation ➢ ➢ ➢ Lo4 Cells release the energy from fuel molecules by oxidation reactions All oxidation reduction (REDOX reactions). Oxidation involves the addition of oxygen or the removal of H atoms or electrons, whereas Reduction involves the addition of H atoms or electrons or the removal of oxygen. 0 ➢ ➢ ➢ ➢ ➢ Lo5 NAD+, NADP+ and FAD are complex molecules containing components that cannot be synthesized in the body and have to be supplied in the diet (vitamins niacin and riboflavin) The total concentration of carrier molecules in cells (oxidized form plus reduced form) is constant. Thus, for example, if all of the NAD in the cell was in the reduced form (NADH), oxidation reactions which require NAD+ would not be possible as there would be no NAD+ available. Thus, carrier molecules must cycle between oxidative and reductive processes if cell function is to be maintained. They therefore act as carrier of reducing power. 0 The reactions that serve to deoxidize reduced carrier molecules include: Cell respiration: NADH and FADH2 formed during catabolism are oxidized in a series of reactions (electron transport) that ultimately reduce oxygen to water (as above). The free energy released is used to drive ATP synthesis and the oxidised carriers (NAD+ & FAD) can be reused in catabolism. Examples: e.g. CH3COCOOH + NADH + H+ CHOHCOOH + NAD+ (Pyruvic acid) (Lactic acid) e.g. Biosynthetic reactions involving reduction steps (use NADPH): fatty acid and cholesterol synthesis require NADPH (biosynthetic reducing power). Lo5 0 Bioenergetics 0 Bioenergetics ➢ ➢ Lo6 In the cell, reactions that release energy (exergonic reactions) are the only ones that occur spontaneously and they provide the energy to drive the energy requiring reactions (endergonic reactions). The energy change in a reaction is known as the enthalpy change (ΔH) and this represents the difference in energy between the products and reactants of a reaction 0 ➢ ➢ Lo6 When energy is released the enthalpy change is given a negative sign (H is-ve). However, not all of the energy released is available to do work. This is because some of the energy may appear in the form of a decrease in entropy (ΔS). 0 ➢ ➢ The energy released in an exergonic reaction that is available to do work isFreeknown asEnergy:free energy (sometimes called Gibbs free energy). The free energy change (ΔG) of a reaction is related to the enthalpy and entropy changes (Δ H and Δ S) by the equation: ΔG = ΔH - T ΔS where T is the temperature in K (oC + 273) 0 Free energy…continue ➢ ➢ Lo6 A reaction can only occur spontaneously when ΔG is -ve i.e. free energy is available to do work. If ΔG is +ve an input of free energy is needed to drive the reaction. 0 Coupling of exergonic to endergonic reactions; the roles of ATP and ADP ➢ ATP and ADP play a major role in coupling the free energy released during the catabolism of fuel molecules to the energy requiring activities of the cell. ➢ ATP and ADP differ only in the number of covalently-liked phosphate groups they contain Lo7 0 Availability of free Energy ➢ The free energy available when fuel molecules are oxidized during catabolism is used to drive the synthesis of ATP from Pi and ADP (eq.). Part of this energy is conserved as the chemical bond energy ➢ This energy is released when the phosphate group is removed by hydrolysis Lo7 0 Amount of ATP and ADP ➢ There is a limited amount of ATP and ADP IN THE CELL and the concentration of ATP is only sufficient for a few seconds of energy requiring cellular activity. ➢ ATP must be rapidly re-synthesized from ADP using the free energy released by the catabolism of fuel molecules. Thus, ATP acts as a carrier of free energy not a store. The rate of ATP turnover in cells is very high as energy is required to drive the various activities that occur in cells. ➢ Lo7 0 High energy and low energy signals ➢ ➢ ➢ ➢ Lo7 Catabolic pathways: Are activated when the concentration of ATP falls and the concentration of ADP and/or AMP increases. Anabolic pathways : Are activated when the concentration of ATP rises. ADP and AMP are low-energy signals because they signal the opposite. Other high-energy signals include NADH, NADPH and FAD2H while Low energy signals include NAD+, NADP+ and FAD. 0 Free energies of hydrolysis and phosphorylgroup transfer potential In addition to ATP a number of other phosphorylated compounds have high energies of hydrolysis (large –ve G0 values). (Energy of position includes energy stored in chemical bonds) Lo7 0 Creatine phosphate The reaction of creatine phosphate with ADP is reversible in muscle cells as in the following: ➢ ➢ ➢ Lo7 When the concentration of ATP is high it can be used to drive the synthesis of creatine phosphate from creatine. ATP can then be regenerated by the reverse reaction when its concentration falls. Creatine phosphate can thus act as a small store of free energy in muscle cells (skeletal & cardiac). 0 ➢ ➢ ➢ ➢ Lo7 This store is important in the first few seconds of vigorous muscle activity such as sprinting. Creatine and creatine phosphate both undergo non-enzymatic chemical changes producing creatinine. Creatinine has no function in the body and is readily excreted via the kidneys in the urine. The rate of production of creatinine is proportional to the concentration of creatine in muscle and this is related to skeletal muscle mass. Measurements of the concentrations of creatinine in blood and urine can also be used as an indicator of kidney function 0 0