Loading tests, metabolic

A1-Waiz M, Ayesh R, Mitchell SC, Idle JR, Smith RL (1989) Trimethylaminuria the detection of carriers using a trimethylamine load test. J Inherit Metab Dis 12 80-85 Al-Waiz M, Mitchell SC, Idle JR, Smith RL (1987) The relative importance of N-oxidation and N-demethylation in the metabolism of trimethylamine in man. Toxicology 43 117-121 Anonymous (1980) Workplace environmental exposure level guide. Trimethylamine. Am Ind Hyg Assoc J 41 A35-A37... 

Metabolic loading tests and the determination of enzyme saturation with cofactor measure the ability of an individual to meet his or her idiosyncratic requirements from a given intake, and, therefore, give a nearly absolute indication of nutritional status, without the need to refer to population reference ranges. A number of factors other than vitamin intake or adequacy can affect responses to metabolic loading tests. This is a particular problem with the tryptophan load test for vitamin Be nutritional status (Section 9.5.4) a number of drugs can have metabolic effects that resemble those seen in vitamin deficiency or depletion, whether or not they cause functional deficiency. 

The tryptophan load test for vitamin Bg nutritional status (the ability to metabolize a test dose of tryptophan) is one of the oldest metabolic tests for functional vitamin nutritional status. It was developed as a result of observation of the excretion of an abnormal-colored compound, later identified as the tryptophan metabolite xanthurenic acid. 

Xanthurenic and kynurenic acids, and kynurenine and hydroxykynurenine, are easy to measure in urine, so the tryptophan load test, the ability to metabolize a test dose of 2 to 5 g (150 to 380 /xmol per kg of body weight) of tryptophan, was widely adopted as a convenient and sensitive index of vitamin Bg nutritional status. 

Early studies of vitamin Be requirements used the development of abnormalities of tryptophan or methionine metabolism during depletion, and normalization during repletion with graded intakes of the vitamin. Although tryptophan and methionine load tests are unreliable as indices of vitamin Be status in epidemiological studies (Section 9.5.4 and Section 9.5.5), under the controlled conditions of depletion/repletion studies they do give a useful indication of the state of vitamin Be nutrition. More recent studies have used more sensitive indices of status, including the plasma concentration of pyridoxal phosphate, urinary excretion of 4-pyridoxic acid, and erythrocyte transaminase activation coefficient. 

Brown et al. (B24) also observed in a few patients, without bladder tumor, that the surgical excision of most of the neoplastic tissue was followed by a return to normal tryptophan metabolism, after the loading test. In cases of bladder cancer, on the other hand, some of the most severe disturbances were observed in patients who had been clinically free of cancer for 1-13 years. 

A preliminary investigation on tryptophan metabolism in aged subjects (over 70 years old) was carried out by Avogaro, Crepaldi, and Parpajola and by Benassi and Allegri, using the tryptophan loading test. 

Thus, an anomaly after tryptophan loading exists in these patients in comparison to normal controls. Other results have been reached by Price et al. (P12) who, by means of their 2 g loading test, found that 6 patients with schizophrenia had a distinctly abnormal tryptophan metabolism while 13 other patients metabolized tryptophan in a normal manner. The patients with abnormal metabolism excreted significantly... 

Raskin (R4) tried the DL-tryptophan (10 g) loading test on 12 patients with infectious hepatitis, 72 with chronic hepatitis following the infectious phase, and 5 with Parkinsons disease. It was shown, by the xanthurenic acid test, that the chronic form was accompanied by a disturbance of tryptophan metabolism, and that xanthurenuria persisted even when amounts of pyridoxine were excreted, i.e., in a state of hyper-vitaminosis. Vitamin Bs was therefore well above the minimal daily requirement of the patients, thus showing that other factors are involved in the abnormal excretion of xanthurenic acid. 

Increased xanthurenic acid excretion after 10 g DL-tryptophan was demonstrated by Lerner et al. (L3) in 3 of 5 patients with rum fits. This metabolic defect was corrected by pyridoxine administration, as observed in a second tryptophan load test. Using the same xanthurenic acid test, significant vitamin Ba deficiency was not observed in patients with alcoholism and associated epilepsy, acute and chronic alcoholism, cirrhosis, acute hallucinosis-tremulousness, acute peripheral neuropathy, Wemicke-Korsakoff syndrome, and nonalcoholic, healthy individuals. It is postulated that pyridoxine deficiency is etiologically related to rum fits (L3). 

The histidine load test is not used in the clinical setting and is only sometimes used by researchers however, a description of this test provides a clear-cut example of how folates behave in the mediation of 1-carbon metabolism. Histidine catabolism takes place in the liver according to the pathway sho vn (Figures 9.16 and 9.17). The intermediates, formiminoglulamic acid and j-forrnirnino-H folate, bear the formimino group —CH hJH. 

Ammonium chloride, bicarbonate, and furosemide loading tests in an epileptic man with metabolic acidosis and episodic hypokalemia taking zonisamide showed evidence of distal renal tubular acidosis (9). On reexamination 7 weeks after zonisamide had been replaced with phenytoin, the renal tubular acidosis had resolved. 

Vezzoli G, Caumo A, Baragetti I, et al. 1999. Study of calcium metabolism in idiopathic hypercalciuria by strontium oral load test. Clin Chem 45(2) 257-261. 

The acid load test is occasionally used for the diagnosis of renal tubular acidosis, conditions in which metabolic acidosis arises from diminished tubular secretion of hydrogen ions. Ammonium chloride is administered orally in gelatin capsules. Urine samples are collected for the following 8 hours. With normal renal function, the pH of at least one sample should be less than 5.3. If necessary in a difficult diagnosis, the excretion rates of titratable acid and ammonium ion. and serum bicarbonate concentration, are all measured. This test should not be perl ormed on patients who are already acidotic or who have liver disease. 

Wl. Wachstein, M., and Gudaitis, A., Disturbance of vitamin Bi metabolism in pregnancy. II. The influence of various amounts of pyridoxine hydrochloride upon die abnormal tryptophan load test in pregnant women. J. Lab. CUn. Med. 42, 98-107 (1953). 

Linder N, Statter M, Leibovici V, et al. 1988. An oral zinc loading test in psoriasis. Metabolism 37 807-809. 

Puls, W., and Keup, U., 1974, Metabolic studies with an amylase inhibitor in acute starch loading tests in rats and men and its influence on the amylase content of the pancreas, in ... 

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