Describe the synthesis and significance of creatine and creatinine.

Creatine — Synthesis

Glycine + Arginine (in the kidney) → Transamidinase → Guanidoacetate → Transported to the liver → Methylation by SAM → creatine → Carried to muscle and brain

• Three amino acids contribute — glycine, arginine and methionine
• Synthesis occurs in two organs: begins in the kidney, completed in the liver
• About 1–2 g is synthesised daily; diet (meat, fish) supplies more
• 95% of body creatine is in skeletal muscle; total pool about 120 g

Creatine Phosphate

Creatine + ATP → creatine kinase → Creatine phosphate + ADP

• A high-energy phosphate reservoir, present at 4–5 times the concentration of ATP
• The immediate energy buffer of muscle — supplies ATP for the first 5–8 seconds of maximal effort, before glycolysis takes over
• The reaction is freely reversible, so it both stores and releases energy

Creatinine — Formation and Excretion

Creatine phosphate → Spontaneous, non-enzymatic, irreversible cyclisation → creatinine → Freely filtered at the glomerulus → Excreted in urine

• Excretion is proportional to muscle mass, not to diet or urine flow — which is what makes it so useful

Clinical Importance

• Serum creatinine is the standard index of renal function
• Creatinine clearance estimates GFR; it slightly overestimates it, since a little creatinine is secreted by the tubule
• It is insensitive early — serum creatinine stays normal until GFR has fallen by about 50% (the "creatinine blind range")
• Used to check the completeness of a 24-hour urine collection
• Creatine kinase is a key diagnostic enzyme — CK-MB in myocardial infarction, CK-MM in muscular dystrophy and rhabdomyolysis

Creatinuria

• Physiological — in children, pregnancy and after delivery
• Pathological — muscular dystrophy, myositis, starvation, hyperthyroidism, uncontrolled diabetes, fever
• The common mechanism is that muscle cannot retain creatine, so it spills into urine

Applied Aspects

• Creatine supplements are widely used by athletes to increase the muscle phosphocreatine pool; they do improve performance in short bursts of high-intensity exercise, though with water retention and weight gain
• Serum creatinine varies with muscle mass — a frail elderly patient may have significant renal impairment with a "normal" value; hence eGFR formulas correct for age and sex
• Cystatin C is an alternative marker independent of muscle mass
• Cooked meat raises serum creatinine transiently, which is why a fasting sample is preferred for accurate assessment