Biochemistry of Creatinine and ATP Metabolism

Creatinine Metabolism

• Creatine phosphate spontaneously cyclizes to form creatinine.
• Creatinine cannot be further metabolized and is excreted in urine.
• The amount of creatinine excreted daily depends on body muscle mass.
• A decrease in muscle mass (e.g., muscular dystrophy or paralysis) leads to decreased creatinine in urine.

ATP Metabolites During Exercise

• ATP is degraded to ADP.
• ADP is partially reconverted to ATP and AMP via the adenylate kinase reaction (2 ADP molecules produce ATP and AMP).
• AMP is either:
  • Deaminated by AMP deaminase to form IMP and ammonia (muscle is a source of ammonia).
  • Dephosphorylated to give adenosine (vasodilator), which increases blood supply to muscles.

Energy Systems

• The body uses all energy systems simultaneously.
• The emphasis on each system changes depending on activity intensity and duration.
• The three energy systems are:
  • Immediate energy: ATP/PC system
  • Short-term energy: Anaerobic glycolysis or lactic acid system
  • Long-term energy: Aerobic system

About Muscles

• Muscles convert chemical energy into mechanical energy.
• This conversion is driven by ATP and creatine phosphate.
• Muscles have a constant supply of chemical energy in the form of ATP and creatine phosphate.
• Movement is controlled by the nervous system, influencing:
  • Speed of contraction
  • Force of contraction
  • Duration of activity
  • Return of muscle to its original state

Muscle Types

• There are three types of muscle cells:
  • Smooth muscle: Non-striated, lines the digestive tract and blood vessels, involuntary control.
  • Skeletal muscle: Striated, attached to bones for movement, voluntary control.
  • Cardiac muscle: Striated, found in the heart, involuntary control.

Structure of Skeletal Muscles

• Skeletal muscle cells (fibers) are long, cylindrical, and run the length of the muscle.
• They are multinucleated (contain hundreds of nuclei) and contain numerous mitochondria (for ATP production).
• Muscle fibers consist of myofibrils arranged in parallel (sarcomeres) embedded in:
  • Sarcoplasm: The cytoplasm of the muscle fiber.
  • Sarcolemma: The excitable plasma membrane surrounding the fiber.
• The muscle cell sarcoplasm contains:
  • Glycogen
  • Glycogenolysis enzymes and Glycolytic enzymes
  • ATP
  • Creatine phosphate

Classification of Skeletal Muscles

• Muscle fibers are classified as either:
  • Slow-twitch (Type I):
    • Contain a large number of mitochondria and myoglobin, giving them a red color.
    • High capacity for ATP production via oxidative phosphorylation (aerobic).
    • Contract slowly but maintain contractions longer than fast-twitch muscles and are resistant to fatigue.
    • Used for repeated contractions of low intensity (e.g., jogging, walking, cycling).
  • Fast-twitch (Type II):
    • Type IIa (red): High myoglobin content, high capacity for ATP production via oxidative phosphorylation (aerobic), used in activities needing speed and strength (e.g., medium weightlifting, medium sprints).
    • Type IIb (white): Few mitochondria and low levels of myoglobin (appear white), main pathway for ATP production is anaerobic glycolysis (fast but unsustainable, leading to fatigue), used for short bursts of speed and strength (e.g., heavy weightlifting, short sprints).

Creatine Synthesis

• Creatine is found in the muscles, providing additional energy supply and adding volume to the body's musculature.
• It is not an essential nutrient as it is naturally produced in the body from glycine and arginine.
• It is also obtained from dietary meat.
• Creatine synthesis begins in the kidney and is completed in the liver:
  • In the kidney, glycine combines with arginine to form guanidinoacetate.
  • Guanidinoacetate travels to the liver, where it is methylated by S-adenosyl methionine to form creatine.
  • Creatine is released from the liver and travels to tissues (brain, heart, skeletal muscle), where it reacts with ATP to form creatine phosphate.
  • This reaction, catalyzed by creatine phosphokinase (CK), is reversible.
  • Cells can use creatine phosphate to regenerate ATP from ADP.
  • The amount of phosphocreatine in the body is proportional to muscle mass (more muscle, more creatine).

Creatine Kinase (CK)

• CK is an enzyme required for the conversion of creatine to phosphocreatine.
• CK has three 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, as it is elevated in acute and chronic muscle diseases.
• Increased CK levels are observed in:
  • Crush injuries (skeletal muscle damage)
  • Myocardial infarction (heart muscle damage)

ATP/PC System (Immediate Energy)

• Primarily used during high-intensity activities lasting less than 10 seconds.
• Examples:
  • 100m sprint
  • 25m swim
  • Smashing a tennis serve
• Requires an immediate and rapid supply of energy:
  • ATP is broken down to ADP + Pi + energy.
  • PC + ADP is converted to creatine + ATP.

Anaerobic Glycolysis/Lactic Acid System (Short-Term Energy)

• Short-term energy system lasting up to 1 minute.
• Used during performances of short duration and high intensity that exceed the energy supplied by phosphagens.
• Examples:
  • 400m sprint
  • 100m swim
  • Multi-sprint sports
• Blood lactate removal occurs through gluconeogenesis: conversion to glucose through the Cori cycle in the liver.

Aerobic Energy System (Long-Term Energy)

• Predominantly used during medium to low intensity activities lasting more than 2-3 minutes.
• Involves the aerobic breakdown of:
  • Glucose:
    • Glycolysis
    • Pyruvate to acetyl CoA
    • Krebs cycle
  • Lipids:
    • Lipolysis (breakdown of lipids)
    • Beta oxidation
    • Krebs cycle