Urine pyruvic acid

Only minimal amounts of a topically applied dose are absorbed through normal stratum corneum. Percutaneously absorbed propylene glycol is oxidized by the liver to lactic acid and pyruvic acid, with subsequent utilization in general body metabolism. Approximately 12-45% of the absorbed agent is excreted unchanged in the urine. 

Disposition in the Body. Readily absorbed after oral administration. It undergoes first-pass acetylation, the extent of which is genetically determined bioavailability 30 to 35% in slow acetylators, 10 to 16% in rapid acetylators. The major metabolites are 3-methyl-l,2,4-triazolo[3,4-a]phthalazine (MTP—the acetylation product) hydralazine pyruvic acid hydrazone (HPH) which is the major plasma metabolite 4-(2-acetylhydra-zino)phthalazin-l-one (A-AcHPZ) which is the major urinary metabolite 3-hydroxymethyl-1,2,4-triazolo[3,4-a]phthalazine (3-OHMTP). About 65% of a dose is excreted in the urine in 24 hours. In rapid acetylators, about 30% is excreted as A-AcHPZ and 10 to 30% as conjugated 3-OHMTP in slow acetylators, about 15 to 20% is excreted as A-AcHPZ and up to 10% as conjugated 3-OHMTP. Other metabolites include phthalazin-1-one (PZ), 1,2,4-triazolo[3,4-fl]phthalazine (TP), 9-hydroxy-MTP, phthalazine, tetrazolo[5,l-a]phthalazine, and hydrazones of hydralazine formed with acetone and a-ketoglutaric acid. About 10% of a dose is eliminated in the faeces. 

Saifer, A., and Harris, A. F., Studies on the photometric determination of phenyl-pyruvic acid in urine. Clin. Chem. 6, 203-217 (1959). 

The concentration of a-ketoglutaric acid is much higher in urine than in blood (the reverse being generally true for pyruvic acid) (B18). 

I.I. Pyruvic Acid. Pyruvic acid is the predominant a-keto acid of human blood, whereas a-ketoglutaric acid predominates in human urine... 

The amount of pyruvic acid excreted in 24 hours has been found in recent works to lie between 2.5 and 11.5 mg (Z2, Z3, TA). As stated before, the amount of pyruvic acid in urine is lower than that of a-ketoglutaric acid Zelnicek (Z3) thus found 8.16 1.55mg/24 hours for pyruvic acid and 14.13 3.20mg/24 hours for a-ketoglutaric acid. 

Many factors aflFecting the pyruvate level in blood and urine, especially muscular exercise, have been studied they have been reviewed previously (A2, L15, M24, P4, S21, T8). Among the newer studies concerning the effect of hormones on blood pyruvate, we shall only mention that the blood level of pyruvic acid is increased after administration of adrenal steroids, which seem to have an inhibitory effect on the utilization of pyruvate (H18). 

We shall focus attention rather on studies concerning the altered blood and urine concentrations of pyruvic acid and of the acids of the tricarboxylic acid cycle, since they are capable of giving information about the still unsolved problem, whether or not there exists a definite disturbance of that cycle during diabetes mellitus. 

Fig. 3.22. GC separation of keto and hydroxy acids from the urine of a patient with maple syrup urine disease. Top chromatogram, the patient before dietary treatment middle chromatogram, the same patient after two days on a diet bottom chromatogram, a mixture of reference compounds. Peaks 1, lactic acid 2, 2-hydroxyisobutyric acid 3, 2-hydroxybutyric acid 4, pyruvic acid 5, 3-hydroxyisobutyric acid 6, 3-hydroxybutyric acid 7, 2-hydroxyisovaleric acid 8, 2-ketobutyric acid 9, malonic acid (internal standard) 10, 2-methyl-3-hydroxybutyric acid 11, 2-hydroxy-n-valeric acid 12. methylmalonic acid 13, 3-hydroxyisovaleric acid 14a and b, 2-ketoisovaleric acid IS, acetoacetic add 16, 2-hydroxyisocaproic acid 17, 2-hydroxy-3-methylvaleric acid 18a, L-2-keto-3-methylvaleric add 18b, D-2-keto-3-methyl-valeric acid 19, 2-ketoisocaproic acid. Reproduced from [386],...

Evidence (104,116) suggests that D-tryptophan is not fully utilized by human subjects and may have harmful effects. Further studies showed that D-tryptophan did not maintain nitrogen balance in normal young men (106), and in another study (117), urine from normal human subjects, after ingestion of D-tryptophan, contained a considerable portion of this compound as well as D-kynurenine. In contrast, the rat utilizes D-tryptophan completely however, food intake is significantly less in D-tryptophan-fed rats than in rats fed a diet containing L-tryptophan (110). The metabolic conversion of the D- to the L-enantiomer takes place in the rat liver and kidney D-amino acid oxidase plays a key role in this conversion (109). Indole pyruvic acid can be converted to L-tryptophan by a stereospecific transaminase apparently absent in humans The chick, on the other hand, utilizes only 7-40% of the D-tryptophan (82,83,110, 113). This wide range of values is probably due to different experimental conditions. D-tryptophan and... 

Acylcamitine profiles indicate elevated long-chain acylcamitines C12, C14, C18, and C18 l, but they also show elevated 3-hydroxyacylcamitines hydroxy-C14, hydroxy-C16, and hydroxy-C 18 1. Urine organic acid analysis shows dicarboxylic acids and 3-hydroxydicarboxylic acids. These latter metabolites can rarely also be observed in certain patients with respiratory chain enzyme deficiencies. Lactate and the lactate to pyruvate ratio are often elevated. The incidence of TCHAD deficiency on newborn screening is estimated at 1 60,000. The diagnosis is usually confirmed by mutation analysis of the genes for the a-chain HADHA and the p-chain HADHB. Enzyme assays are nowadays rarely available. 

A. Harman Alkaloids. Harman is formed in plants by the reaction of tryptamine with pyruvic acid on the pathway shown in Fig. 258. 1,2,3,4-Tetrahydro-jff-carboline was found in the urine of humans (E 1). It is probably formed from tryptamine and formaldehyde. 

Examples are the transformation of pyruvic acid under anaerobic conditions to ethanol, e.g. in yeast, or lactic acid, e.g., in the muscles of animals (D 2), and the transformation of acetyl Co A to acetoacetate or acetone (D 3.1), compounds which are excreted with the urine in diabetic persons (Table 60). 

Histidinemia is a rare hereditary disease characterized by high levels of histidine in blood and urine [92-94]. Affected patients often have speech deficiencies, and excessive amounts of imidazole pyruvic acid are found in the urine. 

The accumulating metabolite is metabolized through alternative pathways, mainly the transaminase reaction. Consequently, imidazole pyruvic acid accumulates in the urine. The imidazole pyruvic, like phenylpyruvic, acid reacts with ferric chloride to yield a blue compound. As a result, the diaper test does not distinguish between phenylketonuria and histidinemia. Yet the diagnosis is of considerable importance because histidinemia is a much more benign disease. Furthermore, histidinemia is not alleviated by withdrawal of phenylalanine from the diet. 

Another important system is NH4-NH3 with pKl 9.24. These are one product of protein catabolism. The acid ion, NH4, can pass through the kidney tubules to be excreted, another means of removing acid from the body. The urine pH varies from about 5 to 7.5 according to the momentary need for elimination of acid in the form of NH4 and also H2PO4. This method, slower than respiration, depends upon recent diet and activity. Citric, lactic, and pyruvic acids and their derivatives are also metabolically important. 

Table F.2 summarizes the metabolites that are observed with NMR in more than 50% of the samples in a body fluid and remain undetected when routine metabolic screening techniques are applied. It is assumed that routine screening comprises measurement of 1. Urine organic acids, amino acids, purines and pyrimidines, monosaccharides and polyols, mucopolysaccharides, oligosaccharides 2. Plasma aminoacids, carnitine (esters), glucose, lactate, pyruvate 3. CSF amino acids and glucose.

The histidinemic urine is sometimes only weakly positive or negative on ferric chloride testing, which reflects either the instability of imidazole-pyruvic acid, the relation of its excretion to protein intake, immaturity of histidine transaminase, or a combination of these factors. Even after histidine loading, histidinemic neonates excrete much smaller quantities of imi-dazolepyruvic acid than do older children. In patients with urocanase deficiency, the levels of blood histidine and urine imidazolepyruvic acid are normal or slightly elevated. Therefore, it is necessary to do a quantitative analysis of blood histidine and urine ferric chloride test in order to overlook the patients with this condition. 

Other clinical symptoms of thiamin deficiency—Additional symptoms of thiamin deficiency include low excretion of thiamin in the urine electrocardiogram changes reduced transketolase activity of the red blood cells and an increase of pyruvic acid in the blood. 

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