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In this article we will discuss about the Creatine and Creatinine:- 1. Occurrence of Creatine and Creatinine 2. Biosynthesis of Creatine and Creatinine 3. Absorption 4. Coefficient 5. Tolerance 6. Creatinuria.
Contents:
- Occurrence of Creatine and Creatinine
- Biosynthesis of Creatine and Creatinine
- Absorption of Creatine and Creatinine
- Creatinine Coefficient
- Creatine Tolerance
- Creatinuria
1. Occurrence of Creatine and Creatinine:
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Creatine is widely distributed in animal tissues. It is present in muscle, brain and blood as phospho-creatine and also in the free state. Skeletal muscle contains about 0.5 per cent creatine and heart muscle about half that amount. 98 per cent of the total creatine in the body is in the muscles.
Creatinine is formed largely in the muscle by the irreversible and non-enzymic removal of water from creatine phosphate. Traces of creatine are also normally present in urine. Creatinine formation is a preliminary step required for the excretion of most of the creatine.
2. Biosynthesis of Creatine and Creatinine:
a. Three amino acids—Glycine, arginine, and methionine—are directly involved.
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b. The first reaction is that of transamidination from arginine to glycine to form guanidoacetic acid (Glycocyamine). This reaction takes place in the kidney but not in the liver or in heart muscle. Recently, evidence has shown that nephrectomized rats can still synthesize creatine. The interpretation is that there is the existence of an external site or sites of transamidination in this animal.
c. The synthesis of creatine is completed in the liver by the methylation of glycocyamine. “Active” methionine is the methyl donor. Other methyl donors betaine or choline after oxidation to betaine— serve indirectly by producing methionine through the methylation of homocysteine.
The methylation of glycocyamine is not reversible. Creatine or creatinine cannot methylate homocysteine to methionine. In the methylation of creatine, ATP and oxygen are required.
The enzymatic mechanisms for the methylation of glycocyamine involves first the formation of active methionine (S-adenosylmethionine) which requires ATP, Mg++ and glutathione as well as a methionine activating enzyme.
The methylation of glycocyamine by active methionine is catalyzed by guanidoacetate methylferase found in the liver of mammals. Glutathione or other reducing substances are required for the optimal activity of the enzyme. There is no evidence for the requirement of metal ions or other cofactors.
It has also been found that the pancreas can synthesize glycocyamine. Therefore, the pancreas may play an important role in the synthesis of creatine within the body of mammals. Dietary creatine or high blood creatine has no effect on the rate of synthesis of creatine in the liver.
The rate of creatine biosynthesis is dependent on kidney transamidinase activity. Hyperthyroidism is associated with reduced kidney transamidinase activity. The effect of hyperthyroidism on kidney transamidinase is mediated by the increased levels of blood creatine.
d. Creatinine is the anhydride of creatine and is formed by the non-enzymatic means in muscle.
The overall reaction is shown in Fig. 20.53.
3. Absorption of Creatine and Creatinine:
It is completely reabsorbed in the renal tubules at lower concentrations.
Normal level of creatine and creatinine in the blood:
Creatine : 2.5-7.3 mg/100 ml
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Creatinine : 0.6-1.2 mg/100 ml
4. Creatinine Coefficient:
This term is used to indicate the number of milligrams of creatinine (plus creatine) nitrogen excreted per kilogram of body weight in 24 hours.
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The creatinine coefficient is an index of the amount of active muscle tissue in the body.
Normal values of creatinine coefficient range from 20 to 26 mg creatinine for men and 14 to 22 mg creatinine for women.
5. Creatine Tolerance:
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a. When 1 or 2 gms of creatine are ingested by a normal adult, about 80 per cent is retained by normal men and about 70 per cent by normal non-pregnant women. About 20 and 30 per cent, respectively, are excreted in the urine during the subsequent 24 hours.
b. Diminished tolerance (i.e. excessive excretion) is present in mild cases of above mentioned disorders.
c. Creatine tolerance is decreased in the majority of patients with hyperthyroidism and increased in hypothyroidism. This procedure carries much values in the diagnosis of hyperthyroidism or hypothyroidism in children.
6. Creatinuria:
Excretion of creatine in urine is said to be creatinuria.
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Creatine excretion occurs in the following conditions:
a. The inability to convert creatine to creatinine in children.
b. In pregnancy, and maximum after parturition in adult females.
c. In febrile conditions.
d. In thyrotoxicosis, probably due to associated myopathies.
e. In muscular dystrophies, myositis, and myasthenia gravis.
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f. In diabetes mellitus with lack of carbohydrate diet.
g. In starvation.
h. In wasting diseases, e.g., in malignancies.
