Leucine excretion

It is perhaps of interest to point out that leucine is a metabolite that, while requiring the expenditure of 2 equivalents of TPNH for its formation from 1.5 equivalents of glucose, results in the production of 3 equivalents of high-energy phosphate, 5 of DPNH, and 3 of carbon dioxide. Thus, leucine excretion might be termed a minor energy-yielding pathway. 

The amounts of single amino acids excreted in urine in the conjugated form, as determined independently by Stein and Muting, are given in Tables 1 and 2. According to Stein, glycine, glutamic acid, aspartic acid, histidine, and proline are quantitatively the most important amino acids liberated in the course of urine hydrolysis. Serine, lysine, tyrosine, cysteine and cystine, threonine, alanine, valine, phenylalanine, and leucine are... 

Stein et al. found in the course of experiments dealing with free and conjugated urinary amino acids in Wilson s disease (S9) that besides a marked aminoaciduria, almost a twofold increase in the excretion of all bound amino acids could be observed. As compared with normal urine (S8), unusual amounts of conjugated leucine, isoleucine, and valine are excreted in cases of Wilson s disease. Also the increase of glutamic acid, aspartic acid, and phenylalanine after urine hydrolysis is much more distinct in this disease than in normal conditions. Other bound amino acids are at or below normal levels. 

Tl. Thompson, R. C., and Kirby, H. M., Variation in the urinary excretion of lysine, threonine, leucine and arginine. Arch. Biochem. Biophys. 21, 210-216 (1949). 

Allyl isovalerate has low irritancy potential. It is deduced that one of its metabolites, isovaleric acid, is toxic, based upon the effects of an inborn error of leucine metabolism caused by isovaleiy l-coenzynie A dehydrogenase deficiency. This is a sx ndrome of neonatal vomiting and lethargy progressing to coma, pancytopenia and ketoacidosis that can be alleviated by glycine treatment, which enhances the synthesis and excretion of iso-valerylglycine (Cohn et al., 1978 lARC, 1985). 

Metabolic Transit. Free Amadori Compounds. It is well known that the synthetic Amadori compounds of the free amino acids are absorbed by the intestine and excreted unchanged in the urine (9,28,30). The transport is not active as observed with deoxyfructosyltryptophan (30) and c-deoxyfructosyllysine (40), and the level of absorption depends on the nature of the amino acid and on the conditions of ingestion. Nutritional assays and metabolic transit studies performed with radioactive Amadori compounds of tryptophan (12,30), leucine (12), and lysine (9,28,41) given orally or intravenously on normal or anti-biotics-treated animals have shown that the intestinal microflora can regenerate part of the amino acid. This can be absorbed subsequently at a very low level by the caecum or the large intestine and incorporated into the tissue proteins or utilized by the intestinal microflora. Barbiroli (13) showed also that some intestinal enzymes were able to liberate some amino acids from their Amadori compounds but to a very small... 

For preparations like mezcalin, histamine, serotonin, thyroxine, it has been shown by Jatzkewitz (11, 76), with mezcalin serving as an example, that in the organism they cannot be split off from the polymeric carrier if they are linked by an amidelike bond to a copolymer from vinylpyrrolidone and acrylic acid, and consequently they cannot be identified anymore either by their activity or by their excretion. By insertion of a so-called spacer group in the form of a dipeptide, as e.g. glycine-leucine, the splitting from such a polymer (14) becomes possible again. 

Individuals who are deficient in HMG-CoA lyase are unable to complete the metabolism of leucine. The increased urinary excretion of 3-hydroxy-3-methylglutaric acids is the primary biochemical criterion that distinguishes this particular enzymatic defect from other defects in enzymes of leucine catabolism that also result in metabolic acidosis and abnormal organic aciduria. There is also substantial urinary excretion of intermediates of leucine catabolism, such as 3-methylglutaconic acid, and their metabolites, including 3-hydroxy-isovaleric acid produced from isovaleric acid. 

Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease The third oxo-add dehydrogenase catalyzes the oxidative decarboxylation of the branched-chain oxo-acids that arise from the transamination of the branched-chain amino acids, leucine, isoleuctne, emd vtdine. It has a similEU subunit composition to pyruvate and 2-oxoglutarate dehydrogenases, and the E3 subunit (dihydrolipoyl dehydrogenase) is the stune protein as in the other two multienzyme complexes. Genetic lack of this enzyme causes maple syrup urine disease, so-called because the bremched-chain oxo-acids that are excreted in the urine have a smell reminiscent of maple syrup. 

Methylcrotonic aciduria. TTiere is, among other things, excess excretion of beta-methylcrotonic acid, a substrate in the course of leucine breakdown. Possibly the defect may lie in the enzyme at this step. Administration of biotin, which normally functions at this step in leucine breakdown, may help improve the symptoms. 

Seawater DOM has numerous sources and sinks and a range of potential reactions. Sources of the sub-micron components include exudation from phytoplankton, microbial degradation of bioparticles, animal wastes (excretion), viral infection of bacteria, sloppy feeding by zooplankton and other animals, and input of dissolved molecules from rivers and surface sediments. Removal mechanisms include photodegradation, sorption to sinking particles, and microbial utilization. Tritiated thymidine and leucine uptake experiments indicate that up to half of the carbon formed by photosynthesis is shunted via dissolved organic molecule intermediates into bacteria. 

Orlistat. Orlistat acts in the GI tract, where it inhibits pancreatic lipases located in the lumen. Systemic exposure of the drug is not required for pharmacological activity. With negligible oral bioavailability (F < 5%), orlistat is primarily excreted unchanged in the feces. However, several metabolites including (40) and (41) have been identified in the plasma of both normal and obese volunteers. These compounds are formed by hydrolysis cf both the N-formyl leucine ester moiety and the lactone ring and do not exhibit any inhibitory activities toward pancreatic lipases (68) (see Fig. 15.1). 

Koleva M (1977) Changes in the urinary excretion of gamma-glutamyltranspeptidase, leucine aminopeptidase and alkaline phosphatase in the combined action of ethylene glycol and high temperature. Probl Khig 3 35-46... 

Liver plays a major role, since it can oxidize all amino acids except leucine, isoleucine, and valine (see Chapter 22). It also produces the nonessential amino acids from the appropriate carbon precursors. Ammonia formed in the gastrointestinal tract or from various deaminations in the liver is converted to urea and excreted in urine (discussed later). 

After orally ingested, L-theanine is absorbed into the blood circulation through the small intestinal tract s brush-border membrane and then distributed to tissues." " It is easily transported into the brain through the blood-brain barrier s leucine-preferring amino acid transporter system L-Theanine does not appear to accumulate. The metabolic fate of theanine after its oral administration was verified to be enzymatically hydrolyzed to glutamic acid and ethylamine in the blood, kidney, liver, and brain then most of the ethylamine generated was immediately excreted into urine, with only a part circulated in plasma. It is completely absent 24 h after administration. 

Roels et al. [38] points out that the analytical techniques identified in Table 1 are not easily available and are not well-suited for routine biomonitoring of occupational or environmental exposures. Instead, indirect biomarkers such as urinary enzymes are often used with success to evaluate mercury exposure and injury. Zalups [35] identifies numerous methods used to detect renal tubular injury induced by mercury. These methods monitor the urinary excretion of enzymes that leak from injured and necrotic proximal tubules, including lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and N-acetyl-P-D-glucosaminidase (NAG). Although advocated by Zalups (35) to detect renal tubular injury, Mason et al. (48) questions the practical utility of such biomarkers in occupational surveillance. According to Mason et al., small increases in NAG, leucine... 

By using colistine for the enrichment procedure, many auxotrophic mutants defective in the biosynthetic pathway of valine and isoleucine have been isolated. From an isoleucine-requiring mutant, defective in threonine desaminase, a prototrophic revertant has been isolated. The threonine desaminase of this revertant differs from the wild type enzyme in that its affinity for isoleucine is diminished. This revertant excretes isoleucine. Another revertant of an isoleucine-deficient mutant was obtained which formed the enzyme acetohydroxy add synthetase constitutively. During heterotrophic growth with fructose or lactate as substrates, valine, isoleucine and leucine were excreted into the culture medium. Approximately 0.6 g of amino acids were produced per liter suspension when lactate was supplied as a substrate under autotrophic conditions the excretion was negligible (Reh, 1970 Fig. 12). 

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