ENERGY METABOLISM Contents EXPLAIN THE CONCEPT OF FOOD AS A FUEL FOR THE PRODUCTION OF ENERGY IN THE BODY, AND HOW ENERGY REQUIREMENTS VARY DURING REST, EXERCISE AND STARVATION. ......................................................................... 1 DESCRIBE THE PATHWAYS INVOLVED IN ENERGY METABOLISM: GLYCOLYSIS, GLUCONEOGENESIS, BETAOXIDATION, AMINO ACID BREAKDOWN, TCA CYCLE AND ELECTRON TRANSPORT CHAIN. FOR EACH, INCLUDE THE CELLULAR LOCATION, THE MAJOR ORGANS IN WHICH EACH PATHWAY IS ACTIVE AND THE EFFECT OF STARVATION ON FLUX OF SUBSTRATES THROUGH THE PATHWAY............................................................................ 2 OUTLINE HOW CHEMICAL ENERGY RELEASED FROM THE OXIDATION OF FOOD MOLECULES IS USED TO DRIVE ATP SYNTHESIS AND DESCRIBE THE ROLE OF THE ELECTRON TRANSPORT CHAIN AS AN INTERMEDIATE IN THIS PROCESS. ................................................................................................................................................................... 4 REFERENCES.............................................................................................................................................................. 5 EXPLAIN THE CONCEPT OF FOOD AS A FUEL FOR THE PRODUCTION OF ENERGY IN THE BODY, AND HOW ENERGY REQUIREMENTS VARY DURING REST, EXERCISE AND STARVATION. Food is a source of fuel for the body as it can be oxidised to produce energy in the body It is a source of “building blocks” for the production of new cells and tissue It is a source of “chemicals” that are necessary to conduct reactions within the body ATP is the energy unit of the body Proteins, lipids and carbohydrates that make up the major part of the food that we eat must be broken down into smaller molecules before cells can use them as energy At rest (The well-fed/ absorptive state) Immediately after a meal, the blood glucose level rises and stimulates the release of insulin Major target for insulin are liver, muscle and adipose tissue Insulin promotes glycogen synthesis in liver and muscle After glycogen stores are filled, the liver converts excess glucose to fatty acids and triglycerides Brain tissue and red blood cells are insulin independent. They derive their energy from oxidising glucose to CO2 and water in both well-fed and normal fasting states. Only in prolonged fasting does this change. Starvation (prolonged) Levels of glucagon markedly elevated Lipolysis is rapid; resulting in excess acetyl CoA that is used for ketone synthesis Levels of both lipids and ketones are thus increased in the blood Muscles use fatty acids as the major fuel and brain adapts to using ketones for some of its energy The shift from glucose to ketones as the major fuel diminishes the amount of protein that must be degraded to Jess Q – Week 9 – A matter of opinion Page 1 support gluconeogenesis. Exercise The primary fuel used to support muscle contraction depends on the magnitude and duration of exercise as well as the major fibres involved Skeletal muscle has stores of both glycogen and some triglycerides During moderately high, continuous exercise, oxidation of glucose and fatty acids are both important, but after 1 to 3 hours of continuous exercise at this level, muscle glycogen stores become depleted and the intensity of exercise declines to a rate that can be supported by oxidation of fatty acids During low-intensity exercise, fat oxidation predominates as the energy source with some contribution by glucose DESCRIBE THE PATHWAYS INVOLVED IN ENERGY METABOLISM: GLYCOLYSIS, GLUCONEOGENESIS, BETAOXIDATION, AMINO ACID BREAKDOWN, TCA CYCLE AND ELECTRON TRANSPORT CHAIN. FOR EACH, INCLUDE THE CELLULAR LOCATION, THE MAJOR ORGANS IN WHICH EACH PATHWAY IS ACTIVE AND THE EFFECT OF STARVATION ON FLUX OF SUBSTRATES THROUGH THE PATHWAY. Jess Q – Week 9 – A matter of opinion Page 2 This diagram is a very basic version of the human body’s metabolic pathway. The different processes are further discussed below Glycolysis - Metabolic pathway that turns glucose into pyruvate - It involves 10 definitive steps and 10 intermediate compounds - Occurs in cytosol of cell - If cell has mitochondria and oxygen, glycolysis is aerobic. If mitochondria or oxygen is lacking, glycolysis may occur anaerobically (eg: exercising skeletal muscle) Gluconeogenesis - Metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate and pyruvate - The process of gluconeogenesis helps keep blood glucose levels within critical limits - Occurs primarily in the liver (cytoplasm and mitochondria) - The pathways are promoted by glucagon and adrenaline and inhibited by insulin. In fasting, glycogen reserves drop dramatically in the first 12 hours, during which time gluconeogenesis increases. After 24 hours, it represents the sole source of glucose. Beta Oxidation - A process in which fatty acids molecules are broken down, through a series of intermediate steps, into acetyl coenzyme A. Acetyl coenzyme A then enters the TCA cycle along with metabolites of carbohydrates and proteins - Pathway is a repetition of four steps. Each four-step cycle releases one acetyl CoA and reduces NAD and FAD (producing NADH and FADH2). - In muscle and adipose tissue (in the mitochondria), Acetyl CoA enters the TCA; in the liver ATP may be used for gluconeogenesis and the acetyl CoA stimulates gluconeogenesis - In a fasting state, the liver produces more acetyl CoA from β oxidation than is used in the citric acid cycle. Much of this acetyl CoA is used to synthesise ketone bodies Amino Acid breakdown - Proteins are made up of amino acids. Thus, to use proteins as a source of fuel, they must be broken back down into amino acids - Amino acids released from proteins usually lose their amino group through transamination or deamination - Body protein is catabolised primarily in muscle and in liver (in the mitochondria) - During prolonged fasting or starvation, protein may be used as an energy source TCA cycle - Occurs in the mitochondria - Primary function is oxidation of acetyl Co A to carbon dioxide - Activity of the TCA is necessary irrespective of the fed or fasting state - Start and end products of the TCA Electron Transport Chain (ETC) Jess Q – Week 9 – A matter of opinion Page 3 - Releases a large amount of energy Occurs in mitochondria Continues in next LO OUTLINE HOW CHEMICAL ENERGY RELEASED FROM THE OXIDATION OF FOOD MOLECULES IS USED TO DRIVE ATP SYNTHESIS AND DESCRIBE THE ROLE OF THE ELECTRON TRANSPORT CHAIN AS AN INTERMEDIATE IN THIS PROCESS. Energy is extracted from food via oxidation This occurs in four stages Stage I - Foods that have been eaten are broken down into their primary components I.e.: Carbohydrates into glucose, Proteins into amino acids and Fats into fatty acids These components are absorbed This occurs in the GIT Stage II - Carbohydrates, proteins and fatty acids are further degraded by different pathways - Carbohydrates are broken down by glycolysis, amino acids by amino acid degradation and fatty acids by β oxidation - All the pathways use a common metabolic intermediate acetyl CoA - Most of the energy at this step is conserved in the chemical bonds of acetyl CoA - A small portion is conserved by reducing NAD to NADH and FAD to FADH2 Stage III - The citric acid (or Krebs or TCA) cycle oxidises CoA to CO2. - The energy released in this process is primarily conserved by reducing NAD to NADH and FAD to FADH2 Stage IV - This stage is oxidative phosphorylation - The energy of NADH and FADH2 is released via the electron transport chain (ETC) - It is used by an ATP synthase to produce ATP - It requires O2 Jess Q – Week 9 – A matter of opinion Page 4 Specific to the ETC - Electrons are transported down a chain coupled to the transport of protons across the inner membrane of the mitochondria - This occurs at three specific proton pumping sites in doing so, creating an electrochemical gradient - Any energy not trapped as ATP is released as heat REFERENCES Hansen, B. & Jorde, L. (N.D). USMLE Step 1 Lecture Notes. USA: Kaplan medical. Sherwood, L. (2004). Human Physiology: From Cells to Systems (5th Edition). Australia: Thompson. Lecture notes: Liver as integrator; Fasting and Exercise; Diet and nutrition Jess Q – Week 9 – A matter of opinion Page 5