Biochemistry of Creatine Metabolism 2024-2025 PDF

Creatine metabolism, high energy phosphates & muscle’s energy supply Dr. Sarray Sameh Ph.D  About muscles Muscle is the major biochemical transducer that convert chemical energy into mechanical energy Have constant supply of...

Creatine metabolism, high energy phosphates & muscle’s energy supply Dr. Sarray Sameh Ph.D  About muscles Muscle is the major biochemical transducer that convert chemical energy into mechanical energy Have constant supply of chemical energy in form of ATP and creatine phosphate Control is operated through nervous systems and involves: speed, force of contraction duration of activity, and return of muscle to the original status,  Muscles types 3 Types of muscle cells: smooth, skeletal & cardiac skeletal muscles (V) (attached to the bone movement) both striated cardiac muscles smooth muscles (non-striated) (lines the digestive tract and blood vessels) Skeletal muscles are under voluntary nervous control, while smooth and cardiac muscles are under involuntary nervous control  Structure of skeletal muscles Are muscles that are attached to bone and facilitate the movement of the skeleton Skeletal muscle cells are long, cylindrical fibers that run the length of the muscle The fibers are multinucleated (contains hundred of nuclei) and contain numerous mitochondria (ATP for contraction & relaxation) Muscle fibers consists of myofibrils arranged in parallel (sarcomeres) and embedded in fluid: sarcoplasm (cytoplasm of muscle fiber), and surrounded by sarcolemma ( excitable plasma membrane) The sarcoplasm of muscle cell contains: - Glycogen - Glycogenolysis enzymes & Glycolytic enzymes - ATP - Creatine phosphate  Classification of skeletal muscles Muscle fibers can be classified as either slow-twitch (Type I) or fast- twitch (type II) - Slow twitch/ type I muscle fibers: Contain large number of mitochondria and myoglobin giving them a red color High capacity for ATP production via oxidative phosphorylation (aerobic) They contract more slowly, but maintain contractions longer, than fast-twitch muscles and are resistant to fatigue Are used for repeated contractions of low intensity like jogging, walking, bicycling -Fast twitch/ type II muscle fibers Can be subdivided as type IIa or type IIb Type IIa fibers: they have high myoglobin content (appear red) High capacity for ATP production via oxidative phosphorylation (aerobic) They are used in activity needing speed and strength like medium weight-lifting and medium sprints Type IIb fibers: have few mitochondria and low levels of myoglobin (appear white). The main pathway for ATP production is anaerobic glycolysis which is fast but not sustainable hence muscles fatigue occurs sooner. They are used in activity needing short bursts of speed and strength like heavy weight-lifting and short sprint.  Creatine synthesis ▪Creatine is found in the muscles: Provides additional energy supply for the muscles Adds volume to the body’s musculature ▪Creatine is not an essential nutrient as it is naturally produced in the human body from Amino acids: glycine and arginine & - Diet: Ingestion of meat Creatine synthesis begins in the kidney and is completed in the liver: -In the kidney, glycine combines with arginine to form guanidinoacetate. - Guanidinoacetate then travels to the liver, where it is methylated by S-adenosyl methionine to form creatine. - The creatine formed is released from the liver and travels through the bloodstream to other tissues, particularly brain, heart, and skeletal muscle, where it reacts with ATP to form the high-energy compound creatine phosphate; This reaction, catalyzed by creatine phosphokinase (CK), and is reversible cells can use creatine phosphate to regenerate ATP from ADP. The amount of phosphocreatine in the body is proportional to the muscle mass  Creatine kinase (CK) ▪CK is required for conversion of creatine into phosphocreatine ▪CK has 3 isoenzymes depending on location: CK-MM mainly in skeletal muscle CK-MB mainly in heart muscle CK-BB mainly in brain ▪CK is of clinical use, it is elevated in acute and chronic muscle diseases; its levels is increased in : Crush injuries (damage of skeletal muscle) Myocardial infarction (damage of heart muscle)  Creatinine metabolism ▪Creatine phosphate is an unstable compound. It spontaneously cyclizes, forming creatinine. ▪ Creatinine cannot be further metabolized and is excreted in the urine. ▪The amount of creatinine excreted each day is constant and depends on body muscle mass. A decrease in muscle mass due to muscular dystrophy or paralysis leads to decreased level of creatinine in urine  ATP metabolites During exercise, ATP is degraded to ADP; ADP in turn is in part reconverted into ATP and AMP via the adenylate kinase reaction (2 ADP molecules to produce ATP and AMP). AMP deaminated by AMP deaminase to form IMP and ammonia (muscle is a source for ammonia) or AMP dephosphorylated to give adenosine (vasodilator) which increase the blood supply to muscles  Energy systems: how the body use them? Energy at any given times is derived from all sources of energy system. However, the emphasis changes depending on the intensity of the activity and the duration; The 3 energy systems are: 1-Immediate energy: ATP/PC 2-Short term energy: anaerobic glycolysis or lactic acid system 3-Long term energy: aerobic system The energy systems all work together at the same time to keep replenishing ATP; At no point will have only one energy system used, but there is often a predominant system  ATP/PC system ATP-PC system is predominantly used during maximum intensity activities lasting no longer than 10 seconds High intensity training (HIT): 100m sprint, 25m swim, smashing a tennis serve.. Require an immediate and rapid supply of energy: ATP ADP+P +energy PC+ADP Creatine+ATP  Anaerobic Glycolysis/ Lactic acid Short term energy system lasting 1 minute During performances of short duration and high intensity that require rapid energy transfer that exceeds that supplied by phosphagens - 400 m sprint - 100m swim - Multi sprint sport Blood lactate removal by gluconeogenesis: conversion to glucose through the Cori cycle in the liver  Aerobic energy system Predominantly used during medium to low intensity activity and for longer duration > 2/3 minutes Aerobic breakdown of glucose: - Glycolysis - Pyruvate into acetyl CoA - Krebs cycle Breakdown of Lipids: - Lipolysis - Beta oxidation - Krebs cycle The END!