Two stages of creatine biosynthesis
The process of creatine formation is strictly divided between two organs and requires three amino acids: arginine, glycine, and methionine.
- Kidneys (Initial stage). Biosynthesis starts with the interaction of arginine and glycine. Under the action of 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 delivered via the bloodstream to the liver. Here, the key methylation reaction takes place—the attachment of a methyl group (-CH3). The active form of methionine, SAM (S-adenosylmethionine), acts as the 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 main target tissues: skeletal muscles and the brain.
Upon entering the cell, creatine undergoes a reversible phosphorylation reaction catalyzed by the enzyme creatine kinase. Interaction with ATP yields creatine phosphate—a crucial high-energy compound—and ADP.
Creatine phosphate acts as a powerful energy buffer. In resting muscle, its content is colossal, exceeding ATP stores by 8 times. When the muscle begins to contract actively, the ATP level remains absolutely stable in the first moments. This is achieved because creatine phosphate instantly transfers its phosphate back to ADP (ATP resynthesis), providing the working muscle with energy during the initial period of exertion. At the same time, the concentration of creatine phosphate itself in the cell drops sharply.
Formation and excretion of creatinine
Unlike most biochemical transformations, the formation of creatinine (creatine anhydride) occurs spontaneously.
A portion of the body's creatine and creatine phosphate pool undergoes continuous non-enzymatic conversion to form a cyclic structure—creatinine. Since this is a final metabolic product, it must be removed from the body and is excreted by the kidneys in the urine.
The normal rate of creatinine excretion for humans is 1–2 g/day (or 8.8–17.6 mmol/day). The constancy of this process makes creatinine an excellent marker for assessing the excretory system.
Clinical and diagnostic significance
Determination of creatine and creatinine levels in blood and urine is widely used in medical practice to diagnose kidney diseases and assess muscle system pathologies. In sports medicine, these parameters serve as a reliable indicator of muscle performance.
Decreased creatinine excretion is an alarming sign. It indicates a reduction in muscle mass against the background of a prolonged negative nitrogen balance and conditions leading to muscle atrophy. Such conditions include:
- Prolonged fasting;
- Acute infectious diseases;
- Diabetes mellitus;
- Hyperthyroidism.
Briefly: answers to topical questions
What are the isoenzymes of creatine kinase, and in which tissues are they localized?
There are three creatine kinase isoenzymes formed by combinations of M (muscle) and B (brain) subunits.
- BB — localized in the brain.
- MM is found predominantly in skeletal muscles.
- MB — localized in the heart muscle (myocardium).
The abbreviation "GAM" can help remember the amino acids for creatine synthesis: Glycine, Arginine, Methionine.
Class and exam questions
Which organs are involved in the synthesis of creatine?
Biosynthesis proceeds in two stages: the first step occurs in the kidneys (formation of guanidinoacetate), and the second in the liver (methylation to creatine).
What is creatinine and how is it formed?
Creatinine is the final product of creatine metabolism (its anhydride). It forms spontaneously, without the participation of enzymes, by the elimination of water or phosphoric acid from creatine and creatine phosphate.
Why do muscles need creatine phosphate?
This high-energy compound acts as an energy reservoir. In the initial period of physical exertion, it provides instantaneous ATP resynthesis, keeping its level constant.
What else to study on this topic
- Mechanism of action of creatine kinase and its isoenzymes in clinical diagnosis
- Metabolic pathway of S-adenosylmethionine (SAM) and its role in other reactions
- Features of nitrogen balance in diabetes mellitus
- Relationship between creatinine levels and renal glomerular filtration
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