Organic acids, urinary excretion

Tyrosine, It has been found that within 7 hours afto the oral administration of dZ-tyrosine to adult human an excess of urinary iyromne and aliphatic organic acids are. excreted which would seem to account for nearly all of the d-component fed. These findings are interpreted to indicate that d(-f-)-tyrosine unlike l —)-tyromne is metabolized in man in such a mimner as to render it unavailable for normal physiolopcal functions (113). 

Chalmers, R.A., Lawson, A.M. and Watts, R.W.E. (1974), Studies on the urinary organic acidic metabolites excreted by patients with )8-methylcrotonylglycinuria, propionic acidemia, and methylmalonic acidaemia, using gas-liquid chromatography and mass spectrometry. Clin. Chim. Acta, 52,43. 

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

Korn, M., Gfrorer, W., Herz, R., Wodarz, I. Wodarz, R. (1992) Stereometabolism of ethylbenzene in man gas chromatographic determination of urinary excreted mandelic acid enatiomers and phenylglyoxylic acid and their relation to the height of occupational exposure. Int. Arch, occup. environ. Health, 64, 75-78 Kostiainen, R. (1995) Volatile organic compounds in the indoor air of normal and sick houses. Atmos. Environ., 29, 693-702... 

Chalmers RA, Roe CR, Stacey , Hoppel CL (1988) Urinary excretion of L-carnitine and acylcarnitines by patients with disorders of organic acid metabolism evidence for secondary insufficiency of L-carnitine. Pediatr Res 18 1325-1328... 

In patients affected with GAMT deficiency, GA is elevated in urine, plasma and CSF. In addition, Cr is decreased or in the low-normal range in urine, plasma and CSF. Creatinine in urine (expressed as excretion per 24 h) and plasma is decreased. This low urinary creatinine results in increased concentration of other metabolites (e.g. amino acids, organic acids, uric acid) when expressed per mol creatinine. During treatment by Cr supplementation, GA in plasma decreases, but does not normalise. Cr in plasma and urine becomes increased. 

On the other hand, acidic drugs tend to ionize under conditions of alkaline pH and so are unable to permeate the renal tubular epithelium and are preferentially excreted. Tire converse applies to conditions of acidic urinary pH. This has been demonstrated experimentally for many drugs weak bases are excreted more rapidly in acidic urine, whereas weak acids are excreted more rapidly in alkaline urine. In the horse, phenylbutazone, which is a weak organic acid with a pKa of 4.6, has a more delayed clearance time under conditions of aciduria than under conditions of alkaline urine. 

Although bile acid conjugates with amino acids are normally excreted into bile, amino acid conjugates of xenobiotics are usually excreted into urine. Conjugation with endogenous amino acids facilitates urinary excretion because of the organic anion transport systems located in the kidney tubules. 

Maitani T, Kubota H, Hori N, et al. 1994. Distribution and urinary excretion of aluminum injected with several organic acids into mice Relationship with chemical state in serum studied by the HPLC-ICP method. J Appl Toxicol 14 257-261. 

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. 

Carnitine deficiency complicates HMG-CoA lyase deficiency and other inborn errors of metabolism, which results in organic acidemia. L-Camitine or P-hydroxy-y-trimethylammonium butyrate is a carrier molecule that transports long-chain fatty acids across the inner mitochondrial membrane for subsequent P-oxi-dation. L-Carnitine also facilitates removal of toxic metabolic intermediates or xenobiotics via urinary excretion of their acyl carnitine derivatives. Indeed, individuals with HMG-CoA lyase deficiency have been shown to excrete 3-methylgluatarylcamitine (Roe et al., 1986). In the absence of ketogenesis, the formation of the acyl carnitine derivative of 3-hydroxy-3-methylglutarate from HMG-CoA also serves to regenerate free CoA in the mitochondria and permits continued P-oxidation of fatty acids. 

Uricosurics, such as probenecid or benz-bromarone (100 mg/day), promote renal excretion of uric acid. They saturate the organic acid transport system in the proximal renal tubules, making it unavailable for urate reabsorption. When underdosed, they inhibit only the acid secretory system, which has a smaller transport capacity. Urate elimination is then inhibited and a gout attack is possible. In patients with urate stones in the urinary tract, uricosurics are contraindicated. 

Urinary excretion of acyl carnitine esters increases considerably in a variety of conditions involving organic aciduria carnitine acts to spare CoA and pantothenic acid (Section 12.2), by releasing the coenzyme from otherwise nonmetabolizable esters that would trap the coenzyme and cause functional pantothenic acid deficiency. 

Although considerable progress has been made in the metabolic profile approach, a number of problems remain to be overcome. Many of these centre around the fluctuations in component composition, not from metabolic disorders, but brought about by other influences. These are principally due to diet and the metabolic variations in individuals in relation to activity. Drugs can also affect the excretion levels of compounds, in addition to the production of their own metabolites. These factors all make quantitative data difficult to obtain and evaluate. Careful statistical analysis of the results are necessary and a population of 500 subjects, grouped in age and sex, has been studied with a view to obtaining a suitable data base for urinary organic acids [370]. 

Penicillins and cephalosporins have short half-lives (0.5-1.5 h) in domestic animals because these antibiotics are secreted by the proximal renal tubules and, due to their high degree of ionization, are not reabsorbed from the distal nephron. The half-lives of lipid-soluble weak organic acids (e.g. sulphadi-methoxine, sulphadiazine, phenobarbitone) and organic bases (e.g. trimethoprim, procainamide, amphetamine) of which a significant fraction (> 20%) of the dose is eliminated by renal excretion may be influenced by the urinary pH reaction. Under acidic urinary conditions, which are normally present in carnivorous species, weak acids are reabsorbed from the distal renal tubules, whereas the excretion of weak bases is enhanced. 

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