Tyrosine, dietary requirement

Of the 20 amino acids in proteins, the body can readily synthesize eight if an appropriate nitrogen source is available. Two others can be synthesized from other amino acids of the diet tyrosine from phenylalanine and cysteine from methionine. The rest must be provided in the diet (Chapter 17), since the body can synthesize none or an insufficient amount. The dietary requirement depends on several factors. Beside essential amino acids, the diet should provide the nitrogen required for synthesis of the nonessential amino acids. 

The requirements for the essential amino acids are further complicated by the finding that two non-essential amino acids can only be synthesized in the body if two of the essential amino acids are present in sufficient amounts. Tyrosine is formed directly from phenylalanine so that the requirement for phenylalanine is less when tyrosine is present than when it is absent firom the diet. Similarly the sulphur that is required for the synthesis of cysteine can only be obtained fi-om methionine so that the dietary requirements for the sulphur-containing amino acids should be considered together. If cysteine is present in ample amounts the requirement for methionine will be minimal, but if cysteine is in short supply more methionine is needed. 

Pyrrolysine trait is restricted to several microbes, and only one organism has both Pyl and Sec. Of the 22 standard amino acids, 8 are called essential amino acids because the human body cannot synthesize them from other compounds at the level needed for normal growth, so they must be obtained from food. In addition, cysteine, taurine, tyrosine, histidine and arginine are semiessential amino-acids in children, because the metabolic pathways that synthesize these amino acids are not fully developed. The amounts required also depend on the age and health of the individual, so it is hard to make general statements about the dietary requirement for some amino acids. 

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

Two amino acids—cysteine and tyrosine—can be synthesized in the body, but only from essential amino acid ptecutsots (cysteine from methionine and tyrosine from phenylalanine). The dietary intakes of cysteine and tytosine thus affect the requirements for methionine and phenylalanine. The remaining 11 amino acids in proteins are considered to be nonessential or dispensable, since they can be synthesized as long as there is enough total protein in the diet—ie, if one of these amino acids is omitted from the diet, nitrogen balance can stiU be maintained. Howevet, only three amino acids—alanine, aspartate, and glutamate—can be considered to be truly dispensable they ate synthesized from common metabolic intetmediates (pyruvate, ox-... 

Tyrosine is formed from phenylalanine by phenylalanine hydroxylase. The reaction requires molecular oxygen and the coen zyme tetrahydrobiopterin, which can be synthesized by the body. One atom of molecular oxygen becomes the hydroxyl group of tyro sine, and the other atom is reduced to water. During the reaction, tetrahydrobiopterin is oxidized to dihydrobiopterin. Tetrahydro biopterin is regenerated from dihydrobiopterin in a separate reaction requiring NADPH. Tyrosine, like cysteine, is formed from an essen tial amino acid and, is therefore, nonessential only in the presence of adequate dietary phenylalanine. 

The liver plays a central role in the synthesis of nearly all circulating proteins. Plasma contains 60-80 g/L of protein and this is turned over at a rate of approximately 250 g/day. A variety of proteins are constructed in the liver using amino acids (Aa) as their basic building blocks. Amino acids are categorised as essential and non-essential , the former being a requirement of dietary intake as they cannot be constructed in vivo, whereas the latter can be synthesised hepatically. The essential amino acids are further categorised as branched-chain amino acids (BCAA leucine, valine, isoleucine) or aromatic amino acids (AAA phenylalanine, tyrosine, methionine) according to their structure. Table... 

Thyroid hormone synthesis requires oxidation of dietary iodine, followed by iodination of tyrosine to mono- and diiodotyrosine coupling of iodotyrosines leads to formation of the active molecules, tetraiodo-tyrosine, (T or L-th3rroxine) and triiodotyrosine (Tj or L-thyronine). 

Transient tyrosinemia is frequently observed in newborn infants, especially those that are premature. For the most part, the condition appears to be benign, and dietary restriction of protein returns plasma tyrosine levels to normal. The biochemical defect is most likely a low level, attributable to immaturity, of 4-hydrox-yphenylpyruvate dioxygenase. Because this enzyme requires ascorbate, ascorbate supplementation also aids in reducing circulating tyrosine levels. 

A small subset of patients with hyperphenylalaninemia show an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) activity but have a deficiency in dihy-dropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydro-biopterin (BH4), a cofactor of PAH (see Fig. 39.18). Less frequently, DHPR activity is normal but a defect in the biosynthesis of BH4 exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, BH4 is also a cofactor for two other hydroxy-lations required in the synthesis of neurotransmitters in the brain the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa (see Chapter 48). It has been suggested that the resulting deficit in central nervous system neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients. 

Hereditary tyrosinaemia type II is caused by a deficiency of tyrosine aminotransferase, leading to eye lesions, skin lesions and neurological complications. The aim of dietary management is to prevent the accumulation of tyrosine and phenylalanine by a low-protein diet. The protein requirements are met by supplementing the diet with a tyrosine- and phenylalanine-free amino acid mixture. 

The proteolytic gut enzymes of H. zea and S. exigua have been shown to be in majority trypsin and in minority chymotrypsin (94), which require basic (lysine and arginine) and aromatic (tyrosine and tryptophan) amino acids, respectively, as sites to hydrolyze protein. Hence, derivatization of these protein-bound or free amino acids by any of the reactive enzyme-products should lead to reduced utilizability of dietary nitrogen. 

The latter value is not much above the estimate of 27 mg per kg per day for phenylalanine plus tyrosine obtained by Nakagawa et al. (1961-1963). The latter values as summarized by the FAO/WHO Committee are shown in Table 2 together with the concentration required in the dietary protein if the requirement is 0.8 gm per kg per day. 

Recommended allowances for infants, children, and adolescents—A dietary allowance of 30 mg per day is recommended from birth to six months, and 35 mg per day from six months to twelve months. This is based on the fact that (1) human milk contains 30 to 55 mg/liter of vitamin C, although it varies with the mother s dietary intake of the vitamin and (2) the breast-fed infant receives approximately 850 ml of milk per day. However, newborn infants, especially if they are premature, may have an increased requirement for the metabolism of tyrosine during the first week of life. 

The most widely known metabolic disorders are those which result in impairment of the intermediary metabolism of nutrients such as proteins, carbohydrates and lipids. For example, phenylketonuria is due to a genetic deficiency of phenylalanine hydroxylase, an enzyme involved in the conversion of phenylalanine to tyrosine. As a result, when ingested in amounts normally encountered in the diet, phenylalanine accumulates in blood and cerebrospinal fluid along with its pyruvate, lactate and acetate derivatives. (See review by McBean and Stephenson. ) The toxic response takes the form of severe mental retardation, neural and dermal lesions and premature death. But phenylalanine is an essential dietary amino acid and cannot be rigorously excluded from the diet, even of sufferers from phenylketonuria, though fortunately they do respond to reduced dietary intakes. Clearly, phenylalanine hydroxylase deficiency narrows the gap between the required intake and that which elicits a toxic response because this pathway is more readily overloaded . 

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