amino acid creatine synthesis

Amino Acid and Their Role in Creatine Synthesis

You may be already heard about the Synthesis of Creatine. If so, did you know it contained amino acid?

Let’s figure out!

During the early 20th century it was first observed that not all of the creatine ingested by animals. All humans could be recovered in the urine as creatinine. This suggested that some of the creatine was retained in the body.

Folin and Denis were among the first to determine that the creatine content of the muscles in cats increased up to 70% after creatine ingestion.

Creatine in humans was soon discovered to be present in part of…

  • skeletal and cardiac muscle
  • uterine and intestinal tissue
  • the testes
  • brain
  • kidney
  • nervous tissue, and…
  • sperm, as well as in adipose stores.

95% of the total creatine pool is found in skeletal muscle tissue. The rest 5% stored in the heart, brain, neural tissues, and testes.

Normal intramuscular values for total creatine are approximately 124.4 mmol/kg.

In 1927, Fiske and Subbarow reported the discovery of a labile phosphorus in the resting muscle of cats. These were subsequently called Phosphoryl Creatine (Phosphocreatine) or, simply, PCr.

This group further observed… during the electrical stimulation of skeletal muscle, PCr diminished only to reappear during recovery.

3 amino acid involved in the creatine synthesis:

  1. arginine
  2. glycine
  3. methionine

The synthesis of creatine begins with the transfer of the amidine group. Starting from arginine to glycine, forming guanidinoacetate and ornithine. This reaction is reversibly catalyzed by the enzyme transaminase.

Creatine is then formed by a non-reversible reaction. This involves the addition of a methyl group. Started from S-adenosylmethionine, with a methyltransferase being required for this process. This step is known as transmethylation.

amino acid

In humans, de novo synthesis of creatine takes place via enzymes located in the liver, pancreas, and kidneys. It also involves the transport to skeletal muscle by the bloodstream after formation.

The total creatine pool in humans is dictated by the combined content of creatine found in both its free and phosphorylated (PCr) form. Of the 95% of the total creatine pool found in skeletal muscle, approximately 40% is free creatine and 60% is PCr.

After skeletal muscle, creatine and PCR are effectively trapped and cannot exit the cell. Until creatine and PCR are degraded to creatinine through non-reversible non-enzymatic processes.

Creatinine is thus filtered in the kidneys and ultimately excreted in the urine. In the absence of dietary intake, normal creatine turnover to creatine is estimated to be about 1.6% per day.

Therefore, in a 70-kg person, the total creatine pool is approximately 120 g, with a total daily turnover of 2 g/day. The body’s creatine pool is maintained via endogenous synthesis and dietary intake.

Although synthesized endogenously and compared with meat consumers. Most vegetarians or those who take part in a creatine-free diet typically have low intramuscular levels.

Like all bodily functions! Creatine metabolism is elegantly regulated by feedback and feedforward mechanisms.

When ingested in the diet, creatine is obtained primarily from muscle tissues (meat or fish), with only trace amounts found in plants.

For example, there are about 2.3 g of creatine per pound of meat (beef, pork) or fish (tuna, salmon, cod).

Herring contains about 3 to 4.5 g of creatine per pound The average intake of creatine in a mixed diet is approximately 1.5 to 2.0 g/day in meat consumers.

The daily needs of vegetarians are met almost exclusively through endogenous pathways. Although it could be speculated that creatine could be sufficiently ingested in a diet heavy in meat products. It has recently been noted that the creatine content in meat decreases with cooking.

When creatinine availability is low, endogenous creatine synthesis is enhanced to keep up the normal levels.

Besides that! When food source from creatine increases, then creatine synthesis is stopped for a while.

Whether produced in the body or ingested, creatine is transported to its primary target tissue (i.e., skeletal muscle) via the circulation. In which uptake takes place through a concentration gradient and/or a specific creatine transporter.

The structural and functional characteristics of creatine to muscle transport have been described.

Creatine appears to enter several types of cells. The sodium­dependent neurotransmitter transport family related to the taurine transporter. It also members of the subfamily of the aminobutyrate-betaine transporters.

Then creatine uptake appears to be enhanced in the presence of insulin and triiodothyronine. But depressed in the presence of the drugs ouabain or digoxin and vitamin E deficiency.

It has also been shown that creatine uptake does not appear to be influenced by… PCr, creatinine, ornithine, glycine, glutamic acid, histidine, alanine, arginine, leucine, methionine, or cysteine concentrations.

The saturable active transport of creatine is highly specific regarding sodium dependence and extracellular creatine concentration.

During uptake, two sodium ions are transported into the cell for every creatine molecule. With the Km (Michaelis constant) for sodium being 55 mM. The Km for creatine uptake ranges from 40 to 90 µm in the rat brain.

In humans, normal Km in monocytes and macrophages appears to be approximately 30 µM.

Human red blood cell creatine uptake appears to be unaffected by an extracellular pH range of 6.9 to 7.9.

In myoblasts (precursors of skeletal muscle cells), the sodium-dependent uptake of creatine in vitro is sensitive to extracellular creatine concentrations.

In this study, cultured myoblasts maintained for 24 hours in a medium containing creatine.

This shown one-third of the uptake activity of cells bathed for the same duration in a medium lacking creatine.

Under normal physiological conditions, the maximum intracellular total creatine pool proposed is about 150 mmol/kg.

Creatine supplementation data by Harris et al. showed that the maximal total creatine pool (creatine and PCr) in creatine-supplemented participants ranged between 140 and 160 mmol/kg.

Once maximized via supplementation, the total creatine pool appears to remain elevated for approximately 21 days without further supplementation.

Intramuscular creatine concentration can be maintained beyond 21 days with small amounts (3 g/day or 0.03 g/kg) of creatine (orally ingested).

In support of these observations, one study to date has demonstrated that following as-day. loading period (typifying the supplemental saturation protocol), performance measures remain elevated for 21 days even without continued supplementation.

Typically, the loading phase is divided into four equal servings per day that consist of approximately 5 g daily for 1 week (0.30 g/kg).

Furthermore, Green et al have shown that creatine plus or more grams of simple carbohydrate increase creatine uptake over taking creatine alone.

Recent data from Stout et al. show that this effect might also occur with lower quantities of carbohydrate (35 g). However, the addition of caffeine might hinder the effects of creatine.

Nonetheless, if an athlete can increase the amount of intramuscular creatine, and more importantly PCr! They should experience an improvement in anaerobic power and capacity.

The availability of PCr is generally accepted to be one of the primary limitations to muscle performance during high­intensity, short-duration exercise.

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