ENERGY SOURCES OF MUSCLES DR. MARWA.pdf

ENERGY SOURCES OF MUSCLES BY/ DR. MARWA KAMEL LECTURER OF MEDICAL BIOCHEMISTRY & MOLECULAR BIOLOGY  OBJECTIVES ❑ Conclude Energy Sources of the muscles. ❑ Illustrate phosphagen system. ❑ Demonstrate Creatine p...

ENERGY SOURCES OF MUSCLES BY/ DR. MARWA KAMEL LECTURER OF MEDICAL BIOCHEMISTRY & MOLECULAR BIOLOGY  OBJECTIVES ❑ Conclude Energy Sources of the muscles. ❑ Illustrate phosphagen system. ❑ Demonstrate Creatine phosphate synthesis & production. ❑ Outline Anaerobic glycolysis as source of muscle energy. ❑ Compare Aerobic respiration as source of muscle energy. ❑ Inspect Oxygen debt. ❑ Categorize Effects of Exercise on Muscle.  Muscle metabolism (Energy Sources) ❑ Muscles need energy to produce contractions. ❑ The energy is derived from: 1. adenosine triphosphate (ATP) present in muscles. Muscles tend to contain only limited quantities of ATP. When depleted, ATP needs to be resynthesized from other sources, namely 2. Creatine phosphate (CP) 3. Muscle glycogen. 4. Other supplies of glycogen are stored in the liver and the human body is also able to resynthesize ATP from lipids, i.e. free fatty acids. ❑ Different modes of energy coverage are used depending on intensity and duration of the workload put on the organism.  Sources of ATP ❑ ATP supplies the energy for muscle contraction to take place. ❑ ATP also provides the energy for the active-transport Ca++ pumps in the SR. Muscle contraction does not occur without sufficient amounts of ATP. ❑ The amount of ATP stored in muscle is very low, only sufficient to power a few seconds worth of contractions. As it is broken down, ATP must be regenerated and replaced quickly to allow for sustained contraction. ❑ There are three mechanisms by which ATP can be regenerated: 1. creatine phosphate metabolism (Phosphagen System) 2. anaerobic glycolysis (Glycogen-lactic acid system) 3. aerobic respiration.  1. Creatine phosphate ❑ Definition: a molecule that can store energy in its phosphate bonds. (High energy compound) ❑ In a resting muscle, excess ATP transfers its energy to creatine, producing ADP and creatine phosphate. ❑ This acts as an energy reserve that can be used to quickly create more ATP. ❑ To replenish the ATP levels quickly, muscle cells use Creatine Phosphate ❑ When the muscle contract and needs energy, creatine phosphate transfers its phosphate back to ADP to form ATP and creatine. ❑ This reaction is catalyzed by the enzyme creatine kinase and occurs very quickly; thus, creatine phosphate-derived ATP powers the first few seconds of muscle contraction.  1.The ATP-CP system ▪ First of two anaerobic energy pathways ▪ Relies on the action of stored ATP and phosphocreatine ▪ Yields enough ATP for 10–15 seconds of energy ▪ Provides highest rate of ATP synthesis  Creatine phosphate Synthesis ❑ Breakdown of a phosphagen such as creatine phosphate enables ATP (adenosine triphosphate) to be generated very quickly without oxygen. ❑ Three amino acids are required: Glycine, Arginine, Methionine (as S-adenosylmethionine). ❑ Site of biosynthesis: ❖ Step 1: Kidneys ❖ Step 2: Liver ❖ From liver, transported to other tissues 98% of creatine are present in skeletal & heart muscles In muscles, creatine is converted to the high energy source creatine phosphate (phosphocreatine)  Creatine phosphate Degradation ❑ The amount of creatine phosphate in the body is proportional to the muscle mass ❑ Creatine and creatine phosphate spontaneously form creatinine as an end product. ❑ Creatinine is excreted in the urine. ❑ Serum creatinine is a sensitive indicator of kidney disease (Kidney function test) i.e. serum creatinine increases with the impairment of kidney function.  2. Anaerobic glycolysis ❑ As the ATP produced by creatine phosphate is depleted, muscles turn to glycolysis as an ATP source. ❑ Glycolysis is an anaerobic (non-oxygen-dependent) process that breaks down glucose (sugar) to produce ATP. ❑ however, glycolysis cannot generate ATP as quickly as creatine phosphate. Thus, the switch to glycolysis results in a slower rate of ATP availability to the muscle. ❑ The sugar used in glycolysis can be provided by blood glucose or by metabolizing glycogen that is stored in the muscle. ❑ ATP is required by our muscles to perform work. When oxygen supplies become limited while exercising, pyruvate will temporarily be converted into lactic acid.  Anaerobic glycolysis (cont.) ❑ With an Inadequate Oxygen Supply Glycolytic (anaerobic) metabolism can provide energy for sudden, rapid, and forceful contractions of some muscles. ❑ Occurs in cytoplasm. ❑ Second anaerobic energy pathway ❑ Provides additional 1–3 minutes in high-level performance ❑ Involves 11 separate biochemical reactions ❑ Uses glucose and glycogen to make ATP ❑ Yields 2 ATP ❑ By product is lactic acid (LA)  Conversion of pyruvate to lactate  In anaerobic condition, pyruvate is reduced to lactate by lactate dehydrogenase (LDH).  In the cells lacking mitochondria and under anaerobic conditions, the NADH⁺ formed in the oxidation of glyceraldehyde 3- phosphate is consumed in the hydrogenation of pyruvate.  The regeneration of NAD + in the hydrogenation of pyruvate to lactate sustains the continued operation of glycolysis under anaerobic conditions.  Significance of Lactate Production  The NADH is obtained from the reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase. The formation of lactate allows the regeneration of NAD+ which can be reused by glyceraldehyde 3-phosphate dehydrogenase.  So Glycolysis proceeds even in the absence of oxygen to supply ATP.  Glycolysis is very essential in skeletal muscle during strenous exercise where oxygen supply is very limited. The cycle involving the synthesis of glucose in liver from the skeletal muscle lactate and the reuse of glucose thus synthesized by the muscle for energy purpose is known as Cori cycle. It is a process in which glucose is converted to Lactate in the muscle and in the liver this lactate is re-converted to glucose. Lactate produced by active skeletal muscle is a major precursor for gluconeogenesis. A  3. Aerobic respiration ❑ In most muscles, especially under conditions of rest or moderate exercise, the supply of oxygen is adequate for aerobic metabolism (fed by fatty acids and by the end products of glycolysis) to supply the energy needs of the contractile system. ❑ > 90 seconds, Occurs in mitochondria, Requires oxygen ❑ Long-term supply of ATP: aerobic cellular respiration (citric acid cycle + oxidative phosphorylation) ❑ Pyruvate oxidized to carbon dioxide ❑ Transfer of chemical bond energy to NADH and FADH2 ❑ Energy used to generate ATP by oxidative phosphorylation ❑ 38 net ATP produced foe each glucose. ❑ Triglycerides also used for aerobic respiration and are the preferential fuel molecules for most skeletal muscle.  Aerobic respiration (cont.) ❑ (The Aerobic Oxidative System) Two Pathways: Krebs Cycle & Electron Transport Chain, It is the most important energy system in the human body as: ❑ Blood lactate levels remain relatively low (3-6mmol/L bl) ❑ Primary source of energy (70-95%) for exercise lasting longer than 10 minutes provided that: a) working muscles have sufficient mitochondria to meet energy requirements b) sufficient oxygen is supplied to the mitochondria c) enzymes or intermediate products do not limit the Kreb’s cycle ❑ Individual energy systems get involved according to the intensity of a movement activity carried out. If the performance is conducted at the maximum level, there is a gradual involvement of all the systems. Lasts 120 seconds and beyond Uses glucose, glycogen, fats, and proteins to make ATP By-products are carbon dioxide (CO2) and water (H2O) ❑ Free fatty acids present in mitochondria of muscle fibres transformed into acetyl CoA are used in the ATP resynthesis. ❑ Acetyl CoA enters the Krebs cycle and thus ATP molecules are generated.  Oxygen debt ❑ Muscle tissue has two sources of oxygen: (1) Oxygen that diffuses into muscle fibers from the blood (2) Oxygen released by myoglobin within muscle fibers. ❑ Oxygen debt is the amount of additional oxygen that must be inhaled following exercise to restore pre-exercise conditions. ❑ Additional oxygen required to: ❖ replace oxygen on hemoglobin and myoglobin ❖ replenish glycogen ❖ replenish ATP and creatine phosphate in phosphagen system ❖ convert lactic acid back to glucose (in the liver)  Effects of Exercise on Muscle ❑ Benefits of aerobic exercise: ❖ Stronger, more flexible muscles, Strengthens the skeleton ❖ Greater resistance to fatigue ❖ Improves aerobic respiration efficiency ❖ Overall body metabolism is more efficient ❖ Improves digestion and elimination ❖ Enhances neuromuscular coordination ❖ The heart enlarges and improves pumping ability ❖ The lungs improve gas exchange efficiency  REFERENCES lippincott illustrated reviews biochemistry For QUESTIONS, PLEASE CONTACT ME ON MAIL [email protected]  A  A