Two Stages of Creatine Biosynthesis
The process of creatine formation is strictly compartmentalized between two organs and requires three amino acids: arginine, glycine, and methionine.
- Kidneys (Initial Stage). Biosynthesis starts with the interaction of arginine and glycine. Catalyzed by the enzyme glycine amidinotransferase, a group transfer occurs, resulting in the formation of guanidinoacetate and ornithine.
- Liver (Methylation Stage). The synthesized guanidinoacetate leaves the kidneys and is transported via the bloodstream to the liver. Here, the key methylation reaction takes place—the addition of a methyl group (-CH3). The active form of methionine, SAM (S-adenosylmethionine), acts as the methyl donor. The enzyme guanidinoacetate N-methyltransferase converts the substrates into finished creatine and S-adenosylhomocysteine (SAH).
Function of Creatine Phosphate in Tissues
From the liver, creatine is transported to its primary target tissues—skeletal muscles and the brain.
Upon entering the cell, creatine undergoes reversible phosphorylation catalyzed by the enzyme creatine kinase. Interaction with ATP yields creatine phosphate—a crucial high-energy compound—along with ADP.
Creatine phosphate functions as a powerful energy buffer. In resting muscle, its concentration is exceptionally high, exceeding ATP stores by 8 times. When a muscle begins active contraction, the ATP level remains entirely stable during the initial moments. This is achieved because creatine phosphate immediately donates its phosphate back to ADP (ATP resynthesis), providing energy to the working muscle during the early phase of exertion. Concurrently, the intracellular concentration of creatine phosphate drops sharply.
Formation and Excretion of Creatinine
Unlike most biochemical transformations, the formation of creatinine (creatine anhydride) occurs spontaneously.
A fraction of the body's creatine and creatine phosphate pool undergoes continuous non-enzymatic conversion to form a cyclic structure: creatinine. Because this is an end product of metabolism, it must be eliminated from the body and is excreted by the kidneys in the urine.
The normal rate of creatinine excretion for an adult is 1–2 g/day (or 8.8–17.6 mmol/day). The constancy of this process makes creatinine an excellent marker for evaluating excretory system function.
Clinical and Diagnostic Significance
Measuring blood and urine levels of creatine and creatinine is widely used in medical practice to diagnose kidney diseases and assess muscular disorders. In sports medicine, these parameters serve as reliable indicators of muscle function.
Decreased creatinine excretion is a red flag. It indicates a reduction in muscle mass associated with prolonged negative nitrogen balance and conditions leading to muscle atrophy. Such conditions include:
- Prolonged starvation;
- Acute infectious diseases;
- Diabetes mellitus;
- Hyperthyroidism.