The enzyme (L-arginine:glycine amidinotransferase (AGAT)) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas. The second enzyme in the pathway (GAMT, Guanidinoacetate N-methyltransferase) is primarily expressed in the liver and pancreas.
Creatine, synthesized in the liver and kidney, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of in skeletal muscle is usually 2-5 mM, which would result in a muscle contraction of only a few seconds. Fortunately, during times of increased energy demands, the phosphagen (or /PCr) system rapidly resynthesizes from with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (CK). Additionally, in most muscles, the regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of are small, changes are difficult to detect because is continuously and efficiently replenished from the large pools of PCr and Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle’s ability to resynthesize from to meet increased energy demands .
Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders. Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (arthritis, congestive heart failure, Parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, and neuroprotection), and depression.
Testosterone levels are one of the key factors in deciding our bodies musculature, definition, overall strength and performance. Serum testosterone levels dictate protein synthesis levels in the body and the amount of lean muscle mass that our bodies are permitted to develop.
The metabolic sensor -activated protein kinase (AMPK) regulates several transport proteins, potentially coupling transport activity to cellular stress and energy levels. The creatine transporter (CRT; ) mediates creatine uptake into several cell types, including kidney epithelial cells, where it has been proposed that is important for reclamation of filtered creatine, a process critical for total body creatine homeostasis. Creatine and phosphocreatine provide an intracellular, high-energy phosphate-buffering system essential for maintaining supply in tissues with high energy demands. Creatine uptake and apical surface biotinylation measurements in polarized S3 cells demonstrated parallel reductions in creatine influx and apical membrane expression after activation with the -mimetic compound 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside. Moreover, may inhibit indirectly via the mammalian target of rapamycin pathway.
inhibits apical membrane expression in kidney proximal tubule cells, which could be important in reducing cellular energy expenditure and unnecessary creatine reabsorption under conditions of local and whole body metabolic stress.
Creatine biosynthetic pathway. h′epatic artery; portal vein; hepatic vein; S-adenosylmethionine; S-adenosylhomocysteine; guanidinoacetate N-methyltransferase; L-arginine:glycine amidinotransferase; guanidinoacetate acid.
The three enzymes shown at the bottom, EC 126.96.36.199, EC 188.8.131.52, and EC 184.108.40.206, are not known to occur in mammals.Return to: