Sulphur amino acid metabolism

Abstract The diet of industrialised countries is usually rich in amino acids, which are partly used as a source of calories. However, metabolic alterations are observed in diseased patients and a preferential retention of Sulphurated Amino Acids (SAA) occurs during the inflammatory response. It has been demonstrated in an acute sepsis phase model in rats that the metabolism of L-Cysteine (Cys) is modified. Glutathione (GSH) concentration is greater in the liver, kidneys and other organs and Cys incorporation into proteins is higher in the spleen and lungs. In the plasma Acute Phase Proteins are released while Albumin is decreased. The pro-inflammatory cytokines such as Interleukin-1, lnterleukin-6 and TNF-a are the main initiators altering protein and amino acid metabolism. 

These changes are induced by a complex intercellular signalling system, whose main constituents are inflammation-associated cytokines. Among other functions. Interleukin-1, Interieukin-6 and Tumour Necrosis Factor-a initiate the alteration of protein and amino acid metabolism designed to support the increased demand of amino acids to sustain the immune response. In particular, lnterleukin-6, stimulates the production of hepatic APP. The relationship with the sulphurated amino acids (SAA) will be discussed in the following chapters. 

However, metabolic alterations are observed under pathological conditions and a preferential retention of sulphur amino acids, evaluated as a urinary sulphur excretion, occurs during an inflammatory response [11-13]. Following a fracture or bums, urinary nitrogen excretion is enhanced to a greater extent than sulphur excretion [14]. Moreover, a... 

J. Martensson, J. Larsson and H. Nordstrom, Amino Acid Metabolism During the Anabolic Phase on Severly Burned Patients w ith Special Reference to Sulphur Amino Acids. Eur J Clinical Invest 17 (1987) 13-15. 

Stress. The information available suggests that stress may increase metabolism of foreign compounds. Diet. The constituents and amount of food (deficiency/starvation) may influence disposition and hence toxicity of chemicals. Food constituents may be enzyme inducers or inhibitors. Lack of food or specific constituents (e.g. protein or vitamins) may decrease metabolic capability, e.g. a protein deficient diet decreases cytochrome P-450 activity. Lack of sulphur amino acids decreases glutathione level. The effect on toxicity will depend on the role of metabolism. 

Metabolism of35S-sulphur amino acids in invertebrates... 

The metabolism of 35S-labelled sulphur amino acids in marine and fresh water invertebrates has been studied and reviewed by Awapara and coworkers179 180. The general conclusion drawn from these studies was that the metabolism of sulphur-bearing amino acids in two molluscs studied is qualitatively the same as in mammals. Taurine, which serves as an osmoregulator in marine molluscs, is formed either by decarboxylation of cysteic acid (in Rangia cuneata) or by oxidation of hypotaurine (in Mytilus edulis), derived from cysteinesulphinic acid by decarboxylation. In Arenicola cristata only the terminal reactions are different. Methionine and cysteine sulphur incorporates into taurocyamine by transamidation between taurine and arginine. 

Homocysteine (Hey) metabolism is closely linked to that of the essential amino acid methionine and thus plays a central role in several vital biological processes. Methionine itself is needed for protein synthesis and donates methyl groups for the synthesis of a broad range of vital methylated compounds. It is also a main source of sulphur and acts as the precursor for several other sulphur-containing amino acids such as cystathionine, cysteine and taurine. In addition, it donates the carbon skeleton for polyamine synthesis [1,2]. Hey is also important in the metabolism of folate and in the breakdown of choline. Hey levels are determined by its synthesis from methionine, which involves several enzymes, its remethylation to methionine and its breakdown by trans-sulphuration. 

In addition to the amino acids found in proteins, the cell also contains a number of other aminp acids that are not normally found in peptides. This includes ornithine, unimportant intermediate in the urea cycle, selenocysteine, a very rare component of some proteins and homocysteine, an important intermediate in sulphur metabolism. 

Hydrogen ions are produced in the body as a result of metabolism, particularly from the oxidation of tlie sulphur-containing amino acids of protein ingested as food. The total amount of hydrogen ion produced each day in this way is of the order of 60 mmoles. If all of this was to be diluted in the extracellular fluid (=14 litres), IH ) would be 4 mmol/1, or 100 000 limes more acid than nonnal This just does not happen, as all the hydrogen ions produced arc efficiently excreted in urine. Everyone who eats a diet rich in animal protein passes a urine w hich is profoundly acid. 

Fig. 12. Reaction of organometallic compounds with nucleophilic sites (H-Nu) of the microbial cell. In this way organometallic compounds interfere with a large number of cell processes. For example, the reaction with essential thiol groups leads to the inhibition of enzymes. However, amines, amides, amino acids and sulphur-free proteins are nucleophilic reaction partners for organometallic compounds, too the corresponding reactions cause disturbances of many kinds in the metabolism of the microbe cell.

A. Yes. Methionine is a sulphur-containing amino acid it is the most important source of labile methyl groups in normal conditions. Its metabolism yields sulphuric acid. 

An inborn error of metabolism in which homocystine is excreted in the urine due to a deficiency of cystathionine synthase, the enzyme which catalyses the formation of cystathionine from homocysteine and serine. Homocysteine is a sulphur containing amino acid and can be detected in the urine by tests for this type of amino acid. Among the symptoms of the condition are minor congenital abnormalities, mental retardation and dislocated lenses. 

The unusual sulphur containing amino acid, hawkinsin , and cis- and transA-hydroxycyclohexylacetic acid observed in an extensively reported patient with transient neonatal tyrosinaemia (Danks et al., 1975 Niederwieser et al., 1977) in whom a defect in 4-hydroxyphenylpyruvate oxidase (see below) had been postulated (Niederwieser et al., 1978) have not been observed in any other patients with tyrosyluria or tyrosinaemia. The origins of these metabolites and their quantitative significance remain questionable, but it is perhaps significant that Bindel et al. (1976) have found 4-hydroxycyclo-hexane-l-carboxylic acid in the urine of several children with suspected metabolic disorders and proposed a dietary source for the metabolite. A bacterial origin also appears possible. 

The pharmacokinetics of amezinium metilsulphate in man have been reported [413-415]. The first step of metabolism consists in demethylation affording the pharmacologically inactive, uncharged 5-amino-2-phenyl-3(2//)-pyridazinone hydroxylated pyridazinones and sulphuric acid conjugates thereof have been isolated [413],... 

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