Biochemistry Lecture 18: Bioenergetics and Metabolism (PDF)

BIOENERGETICS AND METABOLISM metabolism is very complicated all are connected Cellular Respiration Bioenergetics - It describes how living organisms acquire and transform energy in order to perform biological work through the study of different biological processes that lead to product...

BIOENERGETICS AND METABOLISM metabolism is very complicated all are connected Cellular Respiration Bioenergetics - It describes how living organisms acquire and transform energy in order to perform biological work through the study of different biological processes that lead to production and utilization of energy (ATP, GTP,.) all neucleotides can store energy e.g CTP Metabolism - It is the summation of chemical reactions involved in maintaining the living state of the organism. - Divided into two categories: Catabolism - the breakdown of molecules to obtain energy Anabolism - the synthesis of all compounds needed by the cells they are both coupled - Metabolism is closely linked to nutrition and the availability of nutrients.  Macromolecules NAD & FAD are H carriers NADP is not used in energy metabolism micromolecules Types of cell respiration - Aerobic cell respiration, with the participation of (O₂) with the production of 30 ATP molecules/glucose molecule; and anaerobic cell respiration, without the participation of (O₂) which uses other inorganic molecules as an oxidant instead with production of only 2 molecules of ATP/glucose molecule. Phases of cell respiration - The three phases of aerobic cell respiration are glycolysis, TCA cycle and electron transport chain. Energy usage: - Synthesis of macromolecules - Muscle contraction - Signal transmittion in neurons - Transport across cell membrane - Heat production ** Fatty acids oxidation is only aorobic. the only anaorbic one is glucose Aorboic needs mitochondia and oxygen Entropy - It is the measure of a system's thermal energy per unit temperature that is unavailable for doing useful work. heat production Enthalpy - It is defined as a state function that depends only on the prevailing equilibrium state identified by the system's internal energy, pressure, and volume, it simplifies the description of energy transfer.under standarized conditions - At constant pressure, the enthalpy changes equals the energy transferred from the environment through heating or work other than expansion work. It is measured as the change in enthalpy ΔH. The ΔH is a positive change in endothermic reactions and negative in heat- releasing exothermic processes. Redox Reaction coupled - An oxidation-reduction reaction is any chemical reaction in which the oxidation number of a molecule, atom, or ion changes by gaining or losing an electron. Oxidation: Loss of electron Electrons = Protons = Hydrogen if oxidation happens alone = Acidosis = loss of enzymes function => thats why it is coupled with reduction High Energy Phosphate - ATP is formed after the binding of one phosphate molecule (phosphorylation) to one ADP molecule for storing energy in the produced ATP molecule. When ATP provides energy to the cellular metabolism, it releases one of its phosphate ions and ADP reappears. - ADP can also release more phosphate ions and generate AMP or even non-phosphorylated adenosine. Adenosine production from ATP is used in tissues that need urgent supply oxygen, such as in the heart during a myocardial infarction (heart attack). This is because adenosine creates a local vasodilator effect, thus providing faster vasodilation than other physiological methods. Oxidative phosphorylation - This is the process in which ATP is formed as a result of the transfer – of electrons from NADH or FADH2 to O2 by a series of electron carriers. Electrons are passed from one member of the transport chain to another in a series of redox reactions.according to electron affenity - Energy released in these reactions is captured as a proton gradient, which is then used to make ATP in a process called chemiosmosis. - Together, the electron transport chain and chemiosmosis make up oxidative phosphorylation. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms ATP production is either by: 1) ETC or 2) substrate level phosphorylation ATP is the general energy molecule. GTP is used in protein synthesis (translation) CTP used in phospholipid UTP Glycogen synthesis * AMP will be conveted to cAMP (second messenger) for water soluble hormones Adenosine is vasodilator 2 ADP ===> 1 ATP + 1 AMP Electron Transport Chain - ETC is a series of complexes that transfer electrons from electron donors to electron acceptors via redox reactions, and couples this electron transfer with the transfer of protons (H+ ions) across a membrane to create an electrochemical proton gradient that drives the synthesis of ATP. - The molecules of ETC include peptides, enzymes, and others. - The final acceptor of electrons in the electron transport chain during aerobic respiration is O2. Co-Q is the collector of electrons Substrate level phosphorylation - The difference between substrate level phosphorylation and oxidative phosphorylation - Substrate-level phosphorylation is directly phosphorylating ADP with a phosphate and energy provided from a coupled reaction. Oxidative phosphorylation is when ATP is generated from the oxidation of NADH and FADH2 and the subsequent transfer of electrons and pumping of protons. always generate 1 ATP Carbohydrates metabolism Stages of Carbohydrate Metabolism Stage 1: Digestion and hydrolysis - break down large molecules to smaller ones that enter the bloodstream.then absorption of micromolecules Stage 2: Degradation - breaks down molecules to two- and three-carbon compounds. Stage 3: Oxidation of small molecules in the citric acid cycle and electron transport provide ATP energy. (disaccridease) Stage 2: Glycolysis the only pathway that can happen under anarobic = Univeral - Glycolysis is a metabolic pathway that degrades glucose (a six-carbon) to pyruvate (a three-carbon molecules). - It is an anaerobic process (no oxygen) and occur in the cytoplasm. - It is divided into two stages: A- five reactions and consume energy B- five reactions that produce energy The Fate of pyruvate produced from glycolysis lactate (anarobic) / AcetylCoa (aorobic) TCA cycle - It needs oxygen, so it occurs in all aerobic organisms. - It is called citric acid cycle or the Krebs cycle. - It generates energy through the oxidation of acetyl-CoA derived from carbohydrates, fats and proteins into CO2 and chemical energy in the form of ATP - It occurs only in mitochondria lactate in muscle = acidosis = Activation of capsacin = Proteolysis lactate will go to liver to be converted to glucose again (gluconeogensis) Acetyl Coa production = Oxidative decarboxylation in the mitochondria excess acetyl Coa will be converted to FA Glycogenesis in liver (120 g) and muscles (400 g) - It is the storing of glucose by converting it to glycogen in liver and muscles. - It operates when high levels of glucose- 6-phosphate are formed in the first reaction of glycolysis. - It does not operate when energy stores (glycogen) are full, which means that additional glucose is converted to body fat Glycogenolysis - Glycogen stores in liver and muscles is broken down to glucose. - Glucose molecules are removed one by one from the end of the glycogen chain to yield glucose-1- phosphate. mutase - It occurs when the blood glucose level is decreasing to less than the lower limit (70 mg%) to compensate this decrease. Gluconeogenesis (so not including Glycogenlysis ) - It is the generation of glucose from certain non-carbohydrate carbon substrates like the metabolic products of carbohydrates, amino acids and lipid. - It occurs when glycogen stores are depleted as a result of starvation or if the body can not utilize glucose as in the case of diabetes Pentose Phosphate Pathway (PPP) - The pentose phosphate pathway is a metabolic pathway parallel to glycolysis. For FA biosynthsis - It generates NADPH and pentoses as well as ribose 5- phosphate, the last one a precursor for the synthesis of nucleotides. Aracidonic, Linolic and linolenic : Polyunsaturated FA TAG: Thermal insulator, support internal organs, energy source Pathways for Glucose Lipid Metabolism - Lipid metabolism is referred to the synthesis and degradation of lipids within the cells, either break down or storage of fats for energy. - These fats are obtained from consuming food and absorbing them or they are synthesized by an animal's liver. - Minimal amount of fat is essential in our food : For essential fatty acids synthesis. Help Fat-soluble vitamins absorption. As a Source of energy: 1 gm supplies 9.1 calories - Just like glucose Metabolism, the end-products of fatty acid metabolism are carbon dioxide, water and ATP. - However, complete combustion of fatty acids requires glucose to convert it in to carbon dioxide, water and ATP, otherwise ketones are produced. Lipid profle: Needs fasting for 16 hours to clear all chylomicrons for neonate (main) Fatty Acid Synthesis De novo - Start in cytoplasm with help of acetyl-CoA and NADPH produced from mitochondria and Pentose phosphate Pathway (PPP) respectively using enzyme fatty acid synthases. - First acetyl-CoA transported from mitochondria through citrate— malate- pyruvate –Shuttle in form of citrate, which further breaks into Acetyl-CoA and Oxaloacetate. - Only small chain fatty acids get synthesized in to cytoplasm, so the synthesis of long chain fatty acids like Triacylglycerol required specialized organ like Liver. - The liver is the major site for converting excess carbohydrates and proteins into fatty acids and triglyceride. The liver synthesizes large quantities of cholesterol and phospholipids. - After synthesis, VLDL lipoproteins are then exported through blood circulation and stored in adipose tissue. - A small fraction is also converted to small ketone molecules that are exported via the circulation to peripheral tissues, where they are metabolized to yield energy - The conversion of carbohydrates to fatty acids is called lipogenesis. - Lipogenesis is the metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipolysis - It is the catabolic process leading to the breakdown of triacylglycerol (TAGs) into FFAs and glycerol. After release into the blood, FFAs are transported and taken up by other tissues to be utilized for β-oxidation and subsequent ATP generation. Some FFAs do not leave the fat cell and are re-esterified into intracellular TAG. - During lipolysis, intracellular TAG undergoes hydrolysis through the action of lipases including HSL, and monoacylglycerol lipase that can hydrolyze TAGs and FAs. - Lipolysis is regulated by the ANS and by several humoral factors, such as catecholamines (phosphorylation of HSL), glucocorticoids, natriuretic peptides, and growth hormone Beta Oxidation of fatty acids - A saturated acyl CoA is degraded by a recurring sequence of four reactions: Oxidation by FAD Hydration Oxidation by NAD+, and Thiolysis by Co ASH - The fatty acyl chain is shortened by two carbon atoms as a result of these reactions, and generation of FADH2, NADH, and acetyl CoA Ketogenesis - It is the biochemical process by which organisms produce a group of substances collectively known as ketone bodies by the breakdown of fatty acids and ketogenic amino acids. - The three ketone bodies, each synthesized from acetyl-CoA molecules, are: Acetoacetate, which can be converted by the liver into β- hydroxybutyrate, or spontaneously turn into acetone Acetone, is generated through the decarboxylation of acetoacetate, either spontaneously or through the enzyme acetoacetate decarboxylase.. β-hydroxybutyrate is generated through the action of the enzyme D-β-hydroxybutyrate dehydrogenase on acetoacetate Protein metabolism - Proteins are too large to be absorbed. The dietary proteins are hydrolyzed to amino acids by proteolytic enzymes, which can be easily absorbed. - Proteolytic enzymes responsible for degrading proteins are produced by three different organs; stomach, pancreas and the small intestine Catabolism Steps of the Amino acids - Step1: Transport of amino acids in to the cells: The transport of amino acids occurs from the extracellular fluids in to the cells by active transport systems, driven by the hydrolysis of ATP. There are seven different transport systems are known for amino acids in the cells. - Step 2: Transamination: It is a very crucial steps of the catabolism, removing of the α-amino group is essential for producing energy from any amino acid after that removal of remaining carbon skeletons is being metabolized. Mechanism: The first step in the catabolism of most amino acids is the transfer of their α-amino group to α-ketoglutarate. The products are an α-keto acid (derived from the original amino acid) and glutamate Step3. Oxidative deamination: - After the transamination reactions that transfer amino groups, oxidative deamination occurs by glutamate dehydrogenase results in the liberation of the amino group as free ammonia from Glutamate. - This reaction is occurs in the liver. - The α-keto acids enter the central pathway of energy metabolism and ammonia in urea synthesis, liberated after oxidative deamination. - Glutamate is a unique amino acid that only undergoes rapid oxidative deamination, that is catalyzed by glutamate dehydrogenase. - The glutamate dehydrogenase of mammalian liver has the unusual capacity to use either NAD+ or NADP+ as cofactor