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Creatine (N-(aminotminomethyI l-N-methy[glycine, molecular weight 1311 is an ammo compound. Figur- 8.96 Creatine


SAM 5-adenosylmethionine

Nutritional summary

Function: The phosphorylated form creatine phosphate provides an instantly available and vital source of energy in muscles and brain.

Requirements: Dietary intake is not necessary; precursors are available from a balanced diet. 1 ligh intakes increase muscle and brain stores slightly and may provide a modest increase in short-term exercise performance.

Food sources: Present in significant amounts only in muscle proteins. Meat contains 300-500mg per serving (lOOg 3,5oz). Milk, eggs, and plant-derived foods do not contain creatine; lacto-ovo vegetarians and vegans have zero intake. Deficiency: Creatine is produced in adequate amounts by the body as long as protein and vitamin (folate, vitamin B12l intakes are adequate.

Excessive intake: While short-term studies have not observed harmful effects on liver, kidney or other functions even at much higher (20 gd for several days. 10g for 8 weeks) than normal dietary intakes, there have been anecdotal reports of deaths, seizures, arrhythmia, ventricular fibrillation, muscle cramping, and other health problems. Long-term health risks of high intakes thus remain a concern.

Endogenous sources

Daily endogenous production of creatine is about 15 mg/kg requiring arginine. glycine. S-adenosy(methionine (SAM), folate, and vitamin B12. Creatine synthesis constitutes a very significant drain on methyl group donors, drawing about 70"» of the available pool (Wyss and Kaddurah-Daouk. 2000). Synthesis begins in the kidney with the rate-limiting condensation of arginine plus glycine to guanidmoacetie acid plus ornithine by glycine amidinotransferase (EC2.1.4.1). The second step is an S-adenosy hneih ion i ne-requ i ri ng reaction, which takes place in the liver and is catalyzed by guanidinoacctatc N-methyltransferase (EC2.1.1.2), Daily arginine intake typically is about 4 g. a similar amount is synthesized from glutamate in the intestinal mucosa.

Dietary sources

The creatine (free plus phosphorylated (content of meat is about 3 5mg/g, which provides about 1 g per day to meat eaters; vegetarians hav e very low intakes, since neither plants nor eggs or dairy products contain significant amounts, if any.

Note: Healing of meats generates a wide variety of creatine-derived carcinogens (Schut and Snyderwine, IW9). One of these is 2-ai n i no-1 -methyl-6-p heny 1 im i -dazo{4,5-b]pyridinc (PhIP), generated by the pyrolysis of creatine in the presence of phenylalanine or tyrosine; another is 2-amino-3,8-dimethylimidazo[4,5-f]qutnoxaline ( MelQx) derived from creatine and glycine (Oguri et al., 1998),

Glycine oh I


nh I

HjjN NH; Afginine

in I he kidneys

Ornithine oh



nh I

hn nh2

Guanidiniutn acetate

SAMe S-Adenosylhomocysleine

in the liver

hn nh; Creatine

Figure 8.97 Endogenous creatine synthesis

Digestion and absorption

Creatine phosphate from the diet is readily cleaved by alkaline phosphatase (F.C3.1.3.1 ) in the proximal intestinal lumen. While il is likely that creatine, but not phosphite real î ne. is absorbed from the small intestine, the mechanism of uptake from the lumen into entcrocytes and export into portal blood remains unclear. The cationic amino acid transporters I and or 2 (SLC7A1 and SLÇ7A2), which have a wide specificity, are iikcly candidates as the conduit for uptake.

Transport and cellular uptake

Blood circulation: Creatine is taken up into muscle and brain cells via the sodium-dependent choline transporter (SLC7A1 : Sehloss et id.. 1994). The existence of distinct sodium-dependent creatine transporters in these and several other tissues lias been demonstrated (Wyss and kaddurah-Daouk. 2000). Rapid phosphorylation by creatine kinase (EC2,7,3.2) effectively traps the highly polar creatine phosphate inside the cell and helps to sustain the several-fold concentration gradient versus the interstitium.


In muscle and many other tissues creatine is phosphorylated by creatine kinase (EC2.7.3.2) during periods of abundant ATP availability. Creatine phosphate can be dephosphorylated by phosphoamidase (EC3.9,1.1). This enzyme might actually be serine threonine specific protein phosphatase (EC3,1.3.1 ft) and or

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