Muscle creatine metabolism

FIGURE 14.21 The structures of creatine and creatine phosphate, guanidiniutn compounds that are important in muscle energy metabolism. 

Fatty acids are clearly larger in size and show markedly slower diffusion velocity than the small water (or creatine) molecules which have been examined so far by diffusion weighted NMR spectroscopy. However, assessment of diffusion properties of lipids could be a key step for further experimental studies of skeletal muscle lipid metabolism. Diffusion properties of FFA and triglycerides are likely different due to differences in molecular weight. In addition, effects of temperature, chemical surroundings, and the mobility of small lipid droplets in the cytosol may also lead to measurable differences in the diffusion characteristics. 

The isotope tracer method for estimating the total muscle mass of an organism by determining the amount of creatinine clearance. The method relies on the fact that muscle creatine phosphate is converted to creatine, and the latter is metabolized into creatinine. 

The association of muscle disease with a disturbance of creatine metabolism is a long-established contribution of biochemistry to this field, and the subject of much investigation in the past. It has been recognized for over half a century that, in contrast with normal adults, patients with nearly all types of muscle disease exhibit a creatinuria. Comprehensive... 

F2. Fitch, C. D., and Moody, L. G., Creatine metabolism in skeletal muscle. V. An intracellular abnormality of creatine trapping in dystrophic muscle. Proc. Soc. Exp. Biol. Med. 132, 219-222 (1969). 

F4. Fitch, C. D., and Sinton, D. W., A study of creatine metabolism in diseases causing muscle wasting. J. Clin. Invest. 43, 444-452 (1964). 

The concentration of creatinine in serum is a function of creatinine production and renal excretion. Creatinine is a product of creatine metabolism from muscle therefore its production is directly dependent on muscle mass. At steady state, the normal serum creatinine concentration is approximately 0.5 to 1.5 mg/dL for males and females. Creatinine is eliminated primarily by glomerular filtration, and as GFR declines, the serum creatinine concentration rises (Fig. 41-2). 

The serum creatinine concentration is dependent on the input function, or formation rate, and output function, or elimination rate. Its formation rate depends on the zero-order production from creatine metabolism, as well as input from other sources such as dietary intake. Creatine metabolism is directly proportional to muscle mass therefore individuals with more muscle mass have a higher serum creatinine concentration at any given degree of kidney function than those with less muscle mass. Exercise is associated with an increase of approximately 10% in the serum creatinine concentration. As the result of minimal muscle mass patients who are cachectic will have very low serum creatinine concentrations, as do those with spinal cord injuries. " Elderly patients and those with poor nutrition may also have low serum creatinine concentrations (<1 mg/dL) secondary to decreased muscle mass. Other factors that influence the serum creatinine concentration include the dietary intake of creatine. During the cooking of meat, some creatine is converted to creatinine, which is rapidly absorbed following ingestion. 

Greenhaff, P.L., Muscle creatine loading in humans procedures and functional and metabolic effects, in 6th Internationl Conference on Guanidino Compounds in Biology and Medicine. Cincinatti, OH, 2001. 

Description of Method. Creatine is an organic acid found in muscle tissue that supplies energy for muscle contractions. One of its metabolic products is creatinine, which is excreted in urine. Because the concentration of creatinine in urine and serum is an important indication of renal function, rapid methods for its analysis are clinically important. In this method the rate of reaction between creatinine and picrate in an alkaline medium is used to determine the concentration of creatinine in urine. Under the conditions of the analysis, the reaction is first-order in picrate, creatinine, and hydroxide. 

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

During the recovery period from exercise, ATP (newly produced by way of oxidative phosphorylation) is needed to replace the creatine phosphate reserves — a process that may be completed within a few minutes. Next, the lactic acid produced during glycolysis must be metabolized. In the muscle, lactic acid is converted into pyruvic acid, some of which is then used as a substrate in the oxidative phosphorylation pathway to produce ATP. The remainder of the pyruvic acid is converted into glucose in the liver that is then stored in the form of glycogen in the liver and skeletal muscles. These later metabolic processes require several hours for completion. 

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). 

Creatine (N-methylguanidoacetic acid) and its phosphorylated form creatine phosphate (a guanidophosphate) serve as an ATP buffer in muscle metabolism. In creatine phosphate, the phosphate residue is at a similarly high chemical potential as in ATP and is therefore easily transferred to ADP. Conversely, when there is an excess of ATP, creatine phosphate can arise from ATP and creatine. Both processes are catalyzed by creatine kinase [5]. 

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