Creatine cyclization

Uric acid is the end product of the purine metabolism. When uric acid excretion via the kidneys is disturbed, gout can develop (see p. 190). Creatinine is derived from the muscle metabolism, where it arises spontaneously and irreversibly by cyclization of creatine and creatine phosphate (see p. 336). Since the amount of creatinine an individual excretes per day is constant (it is directly proportional to muscle mass), creatinine as an endogenous substance can be used to measure the glomerular filtration rate. The amount of amino acids excreted in free form is strongly dependent on the diet and on the ef ciency of liver function. Amino acid derivatives are also found in the urine (e.g., hippu-rate, a detoxification product of benzoic acid). 

In resting muscle, creatine phosphate forms due to the high level of ATP. If there is a risk of a severe drop in the ATP level during contraction, the level can be maintained for a short time by synthesis of ATP from creatine phosphate and ADP. In a nonenzymatic reaction [6], small amounts of creatine and creatine phosphate cyclize constantly to form creatinine, which can no longer be phosphorylated and is therefore excreted with the urine (see p. 324). 

A compound that includes a carbonyl group on the imidazoline ring is described as sedative. Treatment of the guanidyl substituted amino acid creatine (87-1) with hydrochloric acid results in cyclization to the iminoimidazolinone creatinine (87-2). Condensation of that intermediate with meta-chlorophenylisocyanate (87-3) leads to the formation of a urea by condensation of the reactive function with the imidazole as its amino tautomer. There is thus obtained fenobam (87-4) [92]. 

Degradation Creatine and creatine phosphate spontaneously cyclize at a slow, but constant, rate to form creatinine, which is excreted in the urine. The amount of creatinine excreted is proportional to the total creatine phosphate content of the body, and thus can be used to estimate muscle mass. When muscle mass decreases for any reason (for example, from paralysis or muscular dystrophy), the creatinine content of the urine falls. In addition, any rise in blood creatinine is a sensitive indicator of kidney malfunction, because creatinine is normally rapidly removed from the blood and excreted. A typical adult male excretes about 15 mmol of creatinine per day. The constancy of this excretion is sometimes used to test the reliability of collected 24-hour urine samples—too little creatinine in the submitted sample may indicate an incomplete sample. 

The first reaction in creatinine formation is the transfer of the amido (or amidine) group of arginine to glycine, forming guanidinoacetate. Subsequently, a methyl group is transferred from the ubiquitous 1-carbon-donor S-adenosylmethionine to guanidinoacetate to produce creatine (from which phosphocreatine is formed), some of which spontaneously cyclizes to creatinine, and is eliminated in the urine. 

In individuals v/ith damaged muscle cells, creatine leaks out of the damaged tissue and is rapidly cyclized, greatly increasing the quantity of circulating and urinary creatinine. 

Creatine phosphate, a storage form for high-energy phosphate, is produced from creatine and ATP. It spontaneously cyclizes to form creatinine, which is excreted in the urine. 

Creatine phosphate spontaneously cyclizes, forming creatinine, which is excreted by the kidney. 

A. The amount of creatine in liver cells determines its rate of synthesis from glycine, arginine, and SAM. In muscle, creatine is converted to creatine phosphate, which is nonenzymati-cally cyclized to form creatinine. The amount of creatinine excreted by the kidneys each day depends on body muscle mass. In kidney failure, the excretion of creatinine into the urine will be low. 

Creatine is formed from glycine, arginine, and methionine. The first step, which is carefully controlled, is in the kidney. The second step is in the liver. Creatine s major action is in the muscle as creatine phosphate, a reserve of high-energy phosphates. Creatine phosphate can spontaneously cyclize to form creatinine, which is excreted in the urine. 

Creatine is synthesized in an interorgan metabolic pathway that spans the kidney and liver. In the kidney, arginine and glycine are condensed to form guanidinoacetate, which is exported from the kidney and taken up by hepatocytes in which it is methylated. Creatine phosphate is chemically rmstable and spontaneously cyclizes to give creatinine and phosphate it cannot be reverted back to creatine, so it is a metabolic end product that is excreted in the urine. Because the size of the creatine phosphate pool is relatively constant, the amount of creatinine produced in 24 h is also relatively constant. Thus, the amoruit of creatinine excreted in the urine is used clinically to gauge renal excretory function. 

Creatine phosphate undergoes slow but spontaneous phosphorolysis during which it irreversibly cyclizes to give creatinine, which is very water-soluble and is excreted in the urine. 

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