Lecture 1.2 - Energy reactions in cells.pdf

Origins and fate of nutrients: ◦Cell nutrients circulating in the blood come from a variety of sources: ‣ The diet ‣ Synthesis in body tissues from precursors (not essential fatty acids or amino acids) ‣ Released from storage in body tissues. ◦They are on t...

Origins and fate of nutrients: ◦Cell nutrients circulating in the blood come from a variety of sources: ‣ The diet ‣ Synthesis in body tissues from precursors (not essential fatty acids or amino acids) ‣ Released from storage in body tissues. ◦They are on their way to body tissues where they undergo various chemical transformations (metabolism) including: ‣ Degradation to release energy - all tissues ‣ Synthesis of cell components - all tissues except azure erythrocytes ‣ Storage - liver, adipose tissue, skeletal muscle ‣ Interconversion to other nutrients - liver, adipose tissue, kidney cortex ‣ Excretion - liver, kidney, lungs Cell nutrients: ◦The blood normally contains a wide range of chemical substances. Some of these are required by the cells of the body (cell nutrients) to maintain normal cell function; others include waste products produced by cells. ◦Clinicians measure some of these substances as an aid to the diagnosis of metabolic diseases and in monitoring patient treatment. ◦The blood concentration of cell nutrients and their waste products is normally held relatively constant, but changes do occur under a variety of situations. Physiological changes are seen after meals, during fasting, starvation, exercise, pregnancy and stress. Pathological changes are seen in diabetes, atherosclerosis, obesity, shock, malnutrition and certain enzyme deficiency states. Cell metabolism: ◦Chemical reactions that occur within cells ◦Many reactions take place in the body but only a few reaction types ◦Reactions are organised into metabolic pathways, which are distinct but integrated ‣ Some metabolic pathways occur in all cells ‣ Others are restricted to some cell types ‣ Some may be further restricted to compartments within cells ◦Anabolism + Catabolism = Metabolism ‣ This is a duel function mechanism, and are interconnected Simple overview of metabolism:  Products of catabolic metabolism: ◦Fuel molecules are metabolised to supply: ‣ 1) Building block materials (sugars, amino acids, fatty acids) Dynamic state of cell components (turnover) Cell growth and division Repair ‣ 2) Organic precursors (acetyl CoA) Allow for inter-conversion of building block material ‣ 3) Biosynthetic reducing power NADH NADPH ‣ 4) Energy for cell function and the synthesis of cell components ATP Biological oxidation: ◦Chemical bond energy of fuel molecules is released by oxidation reactions ◦Oxidation - removal of electrons (e-) or removal of H atoms (H+ + e-) ◦All oxidation reactions are accompanied by a reduction reaction, known as REDOX REACTIONS. Biological oxidation - H-carrier molecules: ◦When fuel molecules are oxidised electrons and protons are transferred to carrier molecules ◦Cycle between oxidative processes and reductive processes ◦Act as carriers of ‘reducing power’ for: ‣ ATP production (e.g. NAD+) ‣ Biosynthesis (e.g. NADPH) ◦The total concentration of carrier molecules in cells (oxidised form plus  reduced form) is constant ◦Complex molecules ‣ Contain components from vitamins (B vitamins) ◦Converted to reduced form by adding two H atoms (H+ + e-) ◦H+ dissociates into solution Bioenergetics: ◦Bioenergetics or biochemical thermodynamics deal with the study of energy changes (transfer and utilisation) in biochemical reactions ◦The reactions are broadly classified as exergonic (energy releasing) and endergonic (energy consuming) ◦The energy actually available to do work (utilisable) is known as free energy (G). This is related to Enthalpy and entropy changes. ◦The energy change as the system moves from its initial state to equilibrium, with no change in temperature and pressure is known as free energy change (deltaG). ◦Exergonic reactions are spontaneous because they release energy; endergonic reactions aren’t spontaneous, as they require more energy to take place. ATP-ADP-AMP: ATP: ◦Energy released in exergonic reactions used to drive: ‣ ADP + Pi ——> ATP ◦Part of free energy conserved as the chemical bond energy of the terminal phosphate group of ATP - ‘High energy’ of bond hydrolysis ◦Limited concentration of ADP and ATP. Only enough for a few seconds. Therefore, must cycle. Only a carrier and not a store. ◦ATP is stable in the absence of specific catalysts - vital. Enables flow of energy to be controlled.. Bioenergetics - importance in biological systems:  ◦ATP is known as a high-energy signal because it signals that the cell has adequate energy levels for its immediate needs. High energies of hydrolysis - creatine phosphate: ◦Important reserve of high energy phosphate which can rapidly produce ATP for muscle contraction under anaerobic conditions ◦At rest, when ATP is abundant, creatine is phosphorylated by creatine kinase to form creatine phosphate. Clinical relevance - creatine kinase (CK): a marker of myocardial infarction: ◦Creatine kinase is made up of two subunits. ◦Different isoform combinations are found in different tissues. ◦One isoform combination is specific to heart muscle. ◦CK-MM at 70% and CK-MB at 25-30% ◦CK is released from cardiac myocytes (cells) when damaged, causes myocardial infarction (heart attack) ◦Appears in blood after a few hours ◦Diagnostic of MI ◦CK rises approximately 6 hours after MI, and may remain elevated for 36-48 hours Clinical relevance - creatinine levels: ◦The rate of production of creatinine is proportional to the concentration of creatine in muscle and this is related to skeletal muscle mass. ◦Efficiently excreted by the kidneys in the urine. ◦Indicative of skeletal muscle mass - increased levels in urine suggest muscle wasting ◦Blood and urine levels are indicators of kidney function. High blood levels + low urine levels indicate reduced kidney function.