GENERAL DISCUSSION OF AMINO ACIDS
This section on AMINO ACIDS will be divided into organized sections with regard to type and function of the various amino acids. In this way I hope to keep confusion to a minimum.
| AROMATIC AMINO ACIDS | SULFUR AMINO ACIDS |
| Phenylalanine | Cysteine and Glutathione |
| Tyrosine | Taurine |
| Tryptophan | Methionine |
| Homocysteine |
| UREA CYCLE AMINO ACIDS | GLUTAMATE AMINO ACIDS |
| Arginine and Citrulline | Glutamic Acid, GABA & Glutamine |
| Ornithine | Proline and Hydroxyproline |
| Aspartic Acid-Asparagine |
| THREONINE AMINO ACIDS | BRANCHED CHAIN AMINO ACIDS (BCCA) |
| Threonine | Leucine |
| Glycine | Isoleucine |
| Serine | Valine |
| Alanine |
| AMINO ACIDS WITH IMPORTANT METABOLITES |
| Lysine |
| Carnitine |
| Histidine |
INTRODUCTION
A protein can be defined as any substance which is made of amino acids in peptide linkage. The word “protein” comes from the Greek protos, “first,” deservedly enough, as it is the basic constituent of all living cells. Protos may also be the root of the name of Proteus, a mythological figure who could change form; appropriately, food protein changes form to become human substance after being eaten. Protein makes up three-fourths of the dry weight of most body cells. Proteins are also involved in the biochemical structure of hormones, enzymes, nutrient carriers, antibodies and many other substances and functions essential to life. Simple proteins made up of only a few amino acids are called peptides. One should note that the word peptide comes from the Greek peptos, “cooked,” a rather poetic way of referring to digestion. Peptides are often no more than digested proteins. Many peptides are absorbed directly into the bloodstream after eating. New roles for these very small proteins are being discovered almost daily, it seems. For example, many peptides work as neurotransmitters and as natural pain-relieving substances in the brain. Scientists now know that protein as peptides can be absorbed immediately, without digestion, into the bloodstream. However, the majority of proteins are broken down into amino acids before absorption. It is these amino acids that are the primary building blocks of human life.
What Is an Amino Acid?
“Protein” is a well-recognized term, while the term “amino acid” can be confusing. Amino acids are made up of a weakly acid molecule group in conjunction with a strongly basic amino molecule group. The mild basicity or acidity of amino acids is too minimal to affect acid-base balance in the body, which is preserved by multitudes of protective buffer systems. Thus we hope the misnomer, “amino acid,” will cease to confuse our readers. Amino acids can be thought of as useful ammoniated vinegars. Glycine, for example, has a more correct chemical name: alpha aminoacetic acid. Since “amino” also means ammonia and acetic acid is vinegar, we can call this amino acid “ammoniated vinegar.” This basic structure found in glycine is common to all amino acids. Smelling salts are usually ammonium carbonate, which can restore sensibility to people who have become faint. Vinegar, when added to salads and other foods, makes the taste of food more palatable. Similarly, some amino acids improve flavor or stimulate the mind. They also can control depression or produce sleep. Eight of the amino acids perform functions indispensable if the body is to stay alive; they are termed “essential” and must be consumed daily by everyone. When acid or “vinegar” portions are removed from the amino acids, the basic amines become messengers in the nervous system. When the amine or ammonium portions are removed, the remaining “acid” can be used for fuel, detoxification, or in many processes throughout the body. The amino acids play innumerable roles in human health and disease.
Essential Amino Acids
The necessity for protein and amino acids in the diet becomes cruelly evident during great famines. Children suffering from kwashiorkor (protein-calorie malnutrition)-with their grossly protruding abdomens, atrophied muscle mass and mental retardation-vividly demonstrate the essential nature of proteins and amino acids. Minimum protein requirements for a healthy adult represent the sum of the requirements for each of the eight essential amino acids, plus sufficient utilizable nitrogen to maintain overall synthesis of nitrogen-containing molecules. Nitrogen is lost in urine, feces, skin, hair, nails, semen and menstrual discharge. Although there are considerable problems in determining a minimum protein requirement, it seems to be on the order of 0.3 to 0.4 gram of protein per kilo (2.2 pounds) of body weight per day or about 30 to 40 grams for the average adult male. This assumes a majority of the protein consumed is high-quality protein and contains all or most of the essential amino acids. The current recommended dietary allowance (RDA) is 44 to 56 grams per day. In America even vegetarian diets contain 80 to 100 grams of protein per day. However, the RDA is far from optimal and is useful only as a minimum requirement. The World Health Organization suggests that a newborn infant needs dietary protein that contains 37 percent of its weight in the form of essential amino acids, whereas for adults the figure is less than half that, or about 15 percent. People often do not realize their need for amino acids, because they are not aware of how busy the human body is. Every second the bone marrow makes 2.5 million red cells. Every four days most of the lining of the gastrointestinal tract and the blood platelets are replaced. Most of the white cells are replaced in ten days. A person has the equivalent of new skin in twenty-four days and bone collagen in thirty years. All this continuous repair work requires amino acids. The fist of the essential amino acids was begun by scientists in the early 1900s. The main essential amino acids are now known to be lysine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan and valine. A person would begin to die without ingesting these amino acids daily, although the gut flora (bacteria) provide small quantities of each of them. This actual continuous low level of synthesis is essential; otherwise, symptoms of their absence would be noticed often throughout the day. Histidine and taurine are also essential amino acids for early growth and development in premature infants and possibly for all neonates. Preterm babies are also known to require cysteine, because the fetal liver cannot convert methionine to cysteine. Determination of the ideal intake of these amino acids is more difficult than determination of the minimum daily requirement. There are many other amino acids besides the essential ones that the human body normally manufactures. These nonessential amino acids may become essential to a particular individual through an inborn error of metabolism. If an enzyme, necessary for the manufacture of a particular amino acid by the body is absent, that amino acid becomes an essential requirement of the diet. Nonessential amino acids can also become essential during disease or stress when there is either increased need and/or increased breakdown of them. Many other amino acids occur in man in very small amounts; as yet little is known about these. Furthermore, peptides (made up of two or more amino acids) are also thought to be essential dietary constituents that the body cannot make, but these peptides are not well understood. In the future the list of essential and nonessential amino acids may well be expanded. Amino acid requirements are vastly increased by disease and by inborn metabolic errors. Virtually all stress states require more amino acids, some more than others do; distinguishing the source of the increased amino acid requirements is often difficult. Burn patients require more amino acids because of oozing wounds, while one type of schizophrenic may have a recently expressed inborn error of metabolism which dictates the need for less wheat gluten or serine Certain cancers can be starved by withholding their “favorite’ amino acids. For example, melanomas consume excessive phenylalanine and tyrosine; reducing these two amino acids in a cancer patient’s diet can slow tumor growth. The understanding and manipulation of required amino acids in the diet is essential in maintaining health and controlling disease.
Metabolism of Amino Acids: An Energy Source
The body breaks down excess amino acids essentially into either fat or sugar to obtain energy. The amino acids which are transferred into sugar are called glycogenic. The amino acids which are broken down into fat are called ketogenic. All amino acids are valuable energy sources.
Inborn Errors of Metabolism: Genetic Diseases
Many important clues about amino acid metabolism come from studies of patients with inborn errors, as they are called. All of the amino acids discussed in this book are involved in biochemical pathways which can malfunction due to genetic disease. These inborn metabolic errors teach about the toxicity of amino acids (which often causes convulsions) and can occur when blood levels are increased five to twenty times above normal. Conversely, other inborn errors can cause deficiency symptoms. An understanding of genetic metabolic errors is revealing the secrets of nutrient interactions among the amino acids. Such studies reveal the basis for mega amino acid therapy, and help explain the reasons why some individuals need 3 grams of tryptophan daily whereas others need an extra gram of phenylalanine daily.
Metabolism within the Brain
The most exciting area of amino acid research is the study of brain metabolism. Communication within the brain and between the brain and the rest of the nervous system occurs through chemical “languages,” called neurotransmitters. There are about fifty such languages; the amino acids, either as precursors, neurotransmitters or peptides account for the majority of them. The central nervous system is almost completely regulated by amino acids and peptides. The brain’s amino acids are now being recognized for their importance, and amino acid therapies are revolutionizing the treatment of psychiatric disease. In each chapter, we describe a particular amino acid’s therapeutic potential in psychiatry and the regulation of brain function.
Amino Acids as Precursors
Amino acids are present and important throughout the body. For example, muscle is very high in protein and amino acids. The heart muscle and other organs derive their structure and function primarily from amino acids. When the brain and other organs such as muscles, “talk” to each other, amino acid-related neurotransmitters are again the primary language. Throughout the body, the amino acids have important functions themselves and as precursors for the manufacture of other important substances. This is the reason that they have so much potential value in medicine and surgery.
Precursor Functions of Some Amino Acids
| Arginine | Spermine, Spermidine, Putrescine |
| Aspartic acid | Pyrimidines |
| Glutamic acid | Glutathione |
| Glycine | ,Purines, Glutathione, Creatine, Phosphocreatine, Tetrapyrroles |
| Histidine | Histamine,Erothioneine |
| Lysine | Cadaverine, Carnitine, Amino-caproic acid |
| Ornithine | Polyamines |
| Methionine | Cysteine, Taurine |
| Serine | Sphingosine, Phosphoserine |
| Tyrosine | Epinephrine, Norepinephrine, Melanin, Thyroxine, Mescaline, Tyramine, Morphine (bacteria), Codeine (bacteria), Papaverine (bacteria) |
| Tryptophan | Nicotinic acid, Serotonin, Kynurenic acid, Indole, Skatole, Indoleacetic acid |
Vitamin – Amino Acid Interactions
Amino acids and vitamins interact in interesting and important ways. Pyridoxine, or vitamin B6, is the most important vitamin for amino acid metabolism because it is the cofactor for the important enzymes called transaminases, which metabolize amino acids. Riboflavin, B2 and niacin, B3 are the next most important vitamins in amino acid metabolism. An example of amino acid-vitamin interactions is the relationship between tryptophan and niacin. Niacin is not really a vitamin, but is actually made by the body from tryptophan. Thus, supplemental niacin can spare tryptophan to serve other purposes within the body. It is worth noting that unlike the pure carbohydrate structure of vitamin C, the B vitamins all contain nitrogen (amino group). They are also acids. In some ways the B vitamins are amino acids, but they are not incorporated into proteins.
Sources of the Essential Amino Acids
Both animal and plant proteins contain the known essential amino acids. The removal of even one essential amino acid from the diet leads rather rapidly to a lower level of protein synthesis in the body and eventually to death. In general, protein from animal sources is of greater nutritional value because animal proteins are complete and contain all of the essential amino acids, plus the nonessential ones. The extent to which a food’s amino acid pattern matches that which the body can use is expressed in the “biological value” of that food. The net protein utilization (NPU) reflects the biological value and the digestibility of a protein-in other words, how much of the protein a person eats is finally available to his body. No food corresponds exactly with the body’s required amino acid pattern, but the amino acids in eggs come closest. Therefore, other proteins’ NPUs can be rated in relation to the marvelous egg. Green vegetables and fruits are generally not considered because of their negligible protein content. The essential amino acids most commonly lacking in plants are lysine, tryptophan and methionine. All cereals are deficient in lysine; corn and rice are also low in tryptophan and threonine. Soybeans and oils are low in methionine. Legumes are low in methionine and tryptophan; peanuts are deficient in methionine and lysine. Poor quality meats seem to have higher concentrations of less essential and sometimes even toxic amino acids, such as serine and proline. Fermented foods, fungi and other sources of protein are being investigated from the amino acid profile point of view. We believe the value shown for tryptophan is too low and the value shown for lysine is too high. The FDA has considered regulating the amino acid patterns of protein sources to insure proper quality of diet (Kirschmann and Dunne, 1984). Another criterion for determining amino acid value is to calculate the percent of usable protein; that is, the proportion of usable protein in relation to the total weight of the food. Meats consist of 20 to 30 percent usable protein, ranging from lamb at the bottom to turkey at the top. Soybean flour is 40 percent protein; most cheeses 30 to 35 percent protein; many nuts and seeds between 20 and 30 percent; and peas, lentils and dried beans between 20 and 25 percent. How much is usable amino acids is not known. Whole grains contain a fairly small quantity of protein (12 percent); but so do milk (4 percent) and eggs (13 percent). Thus, in evaluating the value of a protein source, both quality and quantity must be considered. Each chapter in our book provides this information about a particular amino acid, enabling laypeople and dieticians to make sophisticated dietary choices to promote health and alleviate disease.
Amino Acid Supplements
Amino acids are used in many different forms; some are free forms or undigested forms. We will devote our time here with only the free or individual forms, which are generally well absorbed throughout the body and brain. All the amino acids can enter the brain; some enter more easily than others do. Phenylalanine enters the most easily, followed by leucine, tyrosine, isoleucine, methionine, tryptophan, histidine, arginine, valine, lysine, threonine, serine, alanine, citrulline, proline, glutamic acid and aspartic acid respectively. The essential amino acids in general are better absorbed into the brain than the nonessential. Amino acids could possibly be better absorbed if they were taken in the forms of di- and tri-peptides. In hospital settings, hydrolysates or peptides are often more useful than free form amino acids. For most physicians, nutritionists, and laypeople, use of the individual L form amino acid supplement is best. However, for methionine and phenylalanine, the DL form is better. D (right) and L (left) simply refer to the direction of light rotation by the molecules of the amino acid. The D forms may actually have to be converted by the body to the L forms before being used. Variant or keto forms of individual amino acids also have potential as supplemental substances, visit cellgivity for more information. Toxicity of amino acids often occurs only at doses 50 to 500 times the therapeutic dose range.
Nutrient-Metabolic Basis of Disease
The study of amino acids is making a significant contribution to the understanding of diseases. Nutritional assessment without measuring plasma amino acids is incomplete, and marginal deficiencies of amino acids are significant. We have begun to outline amino acid patterns and deficiencies found in many diseases. Amino acid profiles contribute to the more general concept of metabolic typing. We have developed amino acid therapies that arrest herpes, improve memory, raise depression, relieve arthritis and stress, prevent aging and heart disease, control allergies and improve sleep, arrest alcoholism, restore hair growth and alleviate many other conditions. The study of amino acids is particularly relevant to all disease, because the body normally uses amino acids to promote health and fight disease. For example, during infection, plasma phenylalanine levels increase significantly. By using amino acid therapies, we are using the body’s natural medicines. This has allowed us to state two important principles of medicine: 1. Imitatio Corporis (Imitation of the Body)-In the practice of medicine, it is wise to imitate the body’s natural healing mechanisms. For example, when we can’t sleep, we need to imitate the body’s usual biochemical mechanism of falling asleep, and to give more of the dietary substances which the body normally uses to put itself to sleep. Every nutrient has at least one therapeutic use in the treatment of disease. Respect for God’s mysterious harmonies is the foundation of good health and of a “physical morality. ” 2. Pfeiffer’s Law– We have found that if a drug can be found to do the job of medical healing, a nutrient can be found to do the same job. When we understand how a drug works, we can imitate its action with one of the nutrients (Table 1-11), For example; antidepressants usually enhanceflav effect of serotonin and epinephrines. We now know that if we give the amino acids tryptophan or tyrosine, the body can synthesize these neurotransmitters, thereby achieving the same effect and imitating or adding to the net effect of these drugs. Nutrients have fewer, milder side effects, and the challenge of the future is to replace or sometimes combine drugs with the natural healers called nutrients. At present, less than 20 percent of the current drugs administered by a physician are effective (Klevax, 1984). All the healers a physician needs are in the body, there for the harvesting by future generations of physicians and scientists. Amino acids are an example of this harvest. Indeed, the proof documenting the need for individual amino acid therapy comes from the study of drugs. Many drugs affect certain amino acid levels. Anticonvulsants, for example, seem to elevate the inhibitory neurotransmitters. Taurine and glycine are increased while glutamic acid and aspartic acid are reduced. Amino acid profiles often reflect a drug’s mechanism of efficacy. We are learning to replace drugs for many difficult medical conditions with amino acids and are finding good results and fewer side effects. We echo the rabbi doctor Maimonides, who wrote a thousand years ago, “The knowledge of nutrition is the most helpful thing in the field of medicine because of the constant need for food during health as well as illness.” Because of their fundamental contributions to body constituents and biochemical functioning, amino acids, particularly the essential ones, may prove even more valuable in the treatment of human disease than minerals, fats or carbohydrates. Amino acids are indeed on the new frontier in medicine. Our clinical experience described in case histories rich with interesting reports of the benefits of amino acid therapy document this belief.