Amino acids And Their Role in Synthesis Of Creatine

Amino Acids and Their Role in Synthesis of Creatine

During the early 20th century it was first observed that not all of the creatine ingested by animals and 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 skeletal and cardiac muscle, uterine and intestinal tissue, the testes, brain, kidney, nervous tissue, and sperm, as well as in adipose stores. Ninety five percent of the total creatine pool is found in skeletal muscle tissue, with the remaining 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, which was subsequently called phosphorylcreatine or, simply, PCr. This group further observed that, during the electrical stimulation of skeletal muscle, PCr diminished only to reappear during recovery.

Three amino acids are involved in the synthesis of creatine: arginine, glycine, and methionine. The synthesis of creatine begins with the transfer of the amidine group from arginine to glycine, forming guanidinoacetate and ornithine. This reaction is reversibly catalyzed by the enzyme transamidinase. Creatine is then formed by a nonreversible reaction involving the addition of a methyl group from S-adenosylmethionine, with a methyl transferase being required for this process. This step is known as transmethylation. In humans, de novo synthesis (path­way synthesizing a biomolecule from simple precursor molecules) of creatine takes place via enzymes located in the liver, pancreas, and kidneys and 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.

Once in skeletal muscle, creatine and PCr are effectively trapped and cannot exit the cell until creatine and PCr are degraded to creatinine via a nonreversible, nonenzymatic process. 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, vegetarians or those partaking in a creatine-free diet typically have low intramuscular levels compared with meat consumers. 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 path ways 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 dietary availability of creatine is low, endogenous synthesis of creatine is increased to maintain normal levels. On the other hand, when dietary availability of creatine is increased, endogenous creatine synthesis is temporarily suppressed. 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 transport to muscle have only recently been described. Creatine appears to enter several types of cells by sodium­dependent neurotransmitter transport family related to the taurine transporter and members of the subfamily of the aminobutyratelbetaine transporters Furthermore, 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 macro phages 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, exhibited 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, he or she 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 high ­intensity, short-duration exercise.

Amino Acids – The Foundations Of Life

Amino acids – they’re the building blocks of proteins. Proteins in turn are the building blocks of just about everything else! Without these vitally important compounds, we wouldn’t exist. So what are amino acids? Let’s start right at the beginning. Before amino acids. Because even amino acids are ‘made’ from something else! Namely nucleotides.

Nucleotides – The Building Blocks Of Amino Acids

Everything boils down to just five base chemicals, or bases. The base chemicals used in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). The fifth one uracil (U) is only found in RNA where it replaces thymine. These base chemicals are used to build nucleotides.

A DNA nucleotide is made up of one of the 4 base chemicals (A / C / G / T) plus a molecule of phosphoric acid and a molecule of sugar. RNA nucleotides are identical except U replaces T. Nucleotides are in turn joined together in sequences of three to form codons. Each codon encodes specifically for one of the amino acids. So the amino acid Methionine for example is encoded as ATG, meaning it contains adenine, thymine and guanine nucleotides in that order.

Twenty Amino Acids Represented By Sixty-One Unique Codons

If you do the math, you’ll discover that these 4 nucleotides can be arranged into 64 unique codons. Even though there are only 20 amino acids! Therefore, some amino acids are represented by more than one codon. Isoleucine for instance can be coded as any one of the following – ATT, ATC or ATA. Each codon only encodes for one amino acid however so you won’t find any other amino acids encoded as ATT, ATC or ATA.

Sixty-one of these codons encode amino acids. The remaining 3 are used as stop codons. Stop codons are used to signal the end of a sequence of codons or protein. A protein is effectively just a long string of codons or amino acids. The body manufactures more than 50,000 different proteins.

Essential And Non-Essential Amino Acids

Amino acids are classified into two groups. Essential amino acids are those our bodies are not able to manufacture so it’s ‘essential’ we obtain them via our diet. The list of essential amino acids are:

  • Isoleucine (eggs, soy, spirulina, dairy)
  • Leucine (cheese, soy, beef, chicken, pork, nuts, seeds, fish, seafood, beans)
  • Lysine (lean beef, cheese, turkey, chicken, pork, soy, fish, shrimp, shellfish, nuts, seeds, eggs, beans, lentils)
  • Methionine (nuts, beef, lamb, cheese, turkey, pork,fish, shellfish, soy, eggs, dairy, beans)
  • Phenylalanine (meat, fish, eggs, cheese, milk)
  • Serine (beef, dairy products, almonds, asparagus, chickpea, cow pea, flax-seed, lentils, sesame seed, walnut, soy beans)
  • Threonine (lean beef, soy, pork, chicken, liver, cheese,shellfish, nuts, seeds, beans, lentils)
  • Tryptophan (turkey, milk, cheese, oats and oat bran, seaweed, hemp seeds, chia seeds, spinach, watercress, soybeans, pumpkin, sweet potatoes)
  • Valine (cheese, soybeans, beef, lamb, chicken, pork, nuts, seeds, fish, beans, mushrooms, and whole grains)

Non-essential amino acids are still ‘essential’ in that we require them for the creation of functioning proteins. Our body however is able to manufacture them so long as the raw ingredients are supplied. The non-essential amino acids are:

  • Alanine (poultry, a variety of fishes, meat, seaweed, eggs, dairy products)
  • Arginine (turkey, pork loin, chicken, pumpkin seeds, soybeans, peanuts, spirulina, dairy)
  • Asparagine (dairy, whey, beef, poultry, eggs, fish, lactalbumin, seafood, asparagus, potatoes, legumes, nuts, seeds, soy, whole grains)
  • Aspartic Acid (dairy, ggs, chicken, pork, beef, fish, walnuts, pistachios, almonds, chestnuts, oats, corn)
  • Cysteine (meat and poultry, eggs, dairy, red peppers, garlic, onions, broccoli, brussels sprout, oats, granola, wheat germ, sprouted lentils)
  • Glutamic Acid (matured cheeses, cured meats, fish sauce, soy sauce and soy protein, mushrooms, ripe tomatoes, broccoli, peas, walnuts)
  • Glutamine (beef, chicken, fish, dairy products, eggs, beans, beets, cabbage, spinach, carrots, parsley, vegetable juices, wheat, papaya, brussel sprouts, celery, kale)
  • Glycine (bone broth, meat, dairy products, poultry, eggs, fish, beans, spinach, kale, cauliflower, cabbage, pumpkin, banana, kiwi)
  • Histidine (Apple, pomogranates, alfalfa, beets, carrots, celery, cucumber, dandelion, endive, garlic, radish, spinach, turnip greens.)
  • Proline (meat, nuts, seafood, dairy products, eggs, fish, asparagus, avocados, bamboo shoots, beans, brewer’s yeast, broccoli rabe, brown rice bran, cabbage, caseinate, chives, lactalbumin, legumes, seaweed, seeds, soy, spinach, watercress, whey, whole grains)
  • Tyrosine (cheese, soybeans, beef, lamb, pork, fish, chicken, nuts, seeds, eggs, dairy, beans, and whole grains)
Amino Acids and Their Role in Synthesis of Creatine
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Originally posted 2016-12-11 10:33:20.

About Donna Morgan

Donna Morgan discovered she had a passion for writing at a very early age. It’s a passion that has led her down a few interesting paths in life, not the least of which is a keen interest in health and fitness. With a young family, good food and nutrition has become something of a crusade and she loves nothing more than sharing her discoveries with her readers.