Creatine

 Creatine

Chemistry-Chemically it is methyl guanidoacetic acid.

Total amount in the body- 90-120 gm in adult, 98% of it is present in the striated muscle as creatine phosphate. Skeletal muscles contain about 0.5% of creatine. It is also found in heart, about 0-25%. Besides it is found in testes, brain and uterus, especially during pregnancy.

Amount in blood-It is present in blood about 10 mg per 100 ml and remain mostly in the red cells. As it is present inside the red cells, it is not filtered. Hence, it is usually not present in the urine.

Origin and formation of creatine

1. Creatine synthesis requires three amino acids, viz., arginine, glycine and methionine (as S-adenosyl methionine).

2. The compound guanidoacetic acid is an intermediate step in the synthesis of creatine.

3. The methyl group of creatine is derived from methionine.

4. The stages in creatine synthesis appear to be as follows: Two organs, i.e., kidneys and liver, are also involved for the complete synthesis of creatine. In kidneys, glycine and arginine react where amidine group (-CNHNH₂) of arginine is transferred to glycine with the formation of guanidoacetic acid (glycocyamine) by the enzyme transamidinase.

Transamidinase enzyme is present only in kidneys and pancreas. But this enzymatic reaction mostly takes place in the kidneys. Methylation of guanidoacetic acid takes place in the liver, because the liver contains the enzyme guanidoacetic methyl transferase.

Guanidoacetic acid is converted into creatine with the help of amino acid, methionine (activated form) in presence of enzyme guanidoacetic methyl transferase and glutathione (GSH). When methyl group of methionine is transferred to guanidoacetic acid to form creatine (methyl guanidoacetic acid), the methionine is converted into S-adenosyl homo cysteine. Activation of methionine takes place by ATP when methionine is converted into S-adenosyl methionine.

Effects of creatine feeding- If creatine is ingested in small amounts (up to 1 gm daily), none is found in the urine, but in moderate amounts (up to 5 gm daily) a little is excreted as creatine and the rest is stored. But if large amounts (say 20gm) of creatine be taken, the major part (15 gm) is excreted as such, another part (4.5 gm) is retained and a small part (0.5 gm) is excreted as creatinine in the urine.

This shows that creatine is not a waste product. It is useful and there is a store for it in the body. Until this reservoir is filled up, no creatine will appear in the urine. Creatine synthesis is dependent on kidney transamidinate activity. Recent studies have indicated that the pancreas may play unique role in the synthesis of creatine within the mammalian body.

Interrelation with Creatinine- These two compounds are closely interrelated. They are readily interconvertible while in solution. Creatinine is anhydride of creatine having one molecule of water less. Acid medium favours the formation of creatinine, whereas alkaline medium favours the formation of creatine. But in vivo creatinine cannot be converted into creatine, although the reverse is the rule.

 

Fate and functions

1. Creatine is converted into creatine phosphate (phosphagen) which takes an essential part in the chemical changes under lying muscular contraction. Creatine, when given in moderate amounts by mouth, disappears completely in the body and nothing appears in the urine. This is supposed to be due to its conversion into creatine phosphate and subsequent storage in the muscles.

2. Creatine certainly has some function in tissues other than muscles but its nature is not known.

3. Creatine is the precursor of Creatinine.

Excretion of creatine- Creatine is not generally present in the urine of normal adult males. But it may be excreted abnormally. Its excretion in the urine is determined by the following factors:

1. Age- Up to the age of puberty it is constantly present in the urine of both sexes. It has been suggested to be due to an increased production of creatine, induced in some unknown way, by the activity of growth impulse. It may also be due to a lower capacity of the undeveloped muscles for creatine storage. There is a third possibility in that the children possess less power to convert creatine into creatinine.

2. Gender-After puberty it is found intermittently in healthy females, which is not related to menstruation.

3. Pregnancy-It is constantly present during pregnancy. It rises to a maximum of 1.5 gm daily after confinement and is probably derived from the involuting uterus. The sex difference of creatine excretion cannot be properly explained. That increased creatine excretion is not due to the less muscular development in females is proved by the fact that it occurs even in women who are highly trained physically. That sex has something to do here is supported by the observation that creatinuria is common in eunuchs. It may be easily induced in old people (naturally with diminished sex functions) by administration of small amount of creatine.

4. Diet-High protein and low carbohydrate diets increase creatine excretion. High protein diet acts by stimulating tissue metabolism due to its high specific dynamic action. Low carbohydrate diet acts indirectly by the absence of its sparing effects upon the breakdown of tissue protein.

5. Increased tissue breakdown-In any condition that increases the breakdown of tissues, especially of striated muscles, as in starvation, pro longed diabetes mellitus, hyperthyroidism, fevers and other wasting diseases which increase the basal metabolic rate, the creatine excretion increased. In certain diseases of muscles (myopathy) where muscles undergo degeneration, a large amount of creatine is excreted. In such conditions, 90% or more creatine appears in an unchanged form in the urine even when it is given by mouth in small amount. This is said to be due to a lower storage capacity of the muscles. It is also probable that in this disease (i.e., myopathy) the reversible enzyme reaction, by which the broken creatine phosphate becomes resynthesized in the muscle, is absent.