Studies of Thiamine Metabolism in Man. Ii. Thiamine and Pyrimidine Excretion With Special Reference to the Relationship Between Injected and Excreted Thiamine in Normal and Abnormal Subjects 1

Abstract

Although numerous attempts have been made to devise tests for thiamine nutrition based upon the urinary excretion of the vitamin after its oral or parenteral administration (1 to 9), the relationship between the dose of the vitamin given and the amount which can be recovered in the urine is obscure. Thiamine administered orally or parenterally rapidly appears in the urine, but the increment in the urine after a single dose represents only a fraction of the total amount given (10, 11, 6) and the fate of the remainder is unknown.The difference between the amount of thiamine administered and the amount excreted may be explained in part by storage of the vitamin in the body. Tissue B, in dogs can be increased by daily injections of the vitamin (12), but the increase is too small to account for the large losses of administered thiamine. In man, studies of tissue thiamine concentration before and after B, administration are not feasible; a few observations on autopsy material from subjects who received thiamine parenterally indicate some storage of the vitamin (13), but not enough to account for the amount of administered thiamine which fails to appear in the urine. Furthermore, administration of B, supplements over a prolonged period should saturate the tissues. Yet even under such conditions (14, 15) urinary thiamine accounts for only a fraction of the total. B, administered.Urine normally contains both thiamine and another substance which accelerates yeast fermentation (16). The urinary concentration of this substance, as well as of thiamine, increases after the oral or parenteral administration of thiamine supplements (14,15,17). Little is known regarding the factors which influence the conversion of the I This investigation was aided by a grant from the Josiah Macy, Jr. Foundation.vitamin to this substance, and the excretion of the latter in relation to thiamine intake also requires elucidation.This investigation was designed to clarify the following points:1. The relation between the intake and excretion of thiamine in normal and abnormal subjects.2. The fate of that portion of administered thiamine which cannot be recovered in the urine.3. The relation between the intake of thiamine and the excretion of the non-thiamine factor which accelerates yeast fermentation. Throughout this paper this substance is referred to as "pyrimidine" or as "PAYF."4. The rate of excretion of excessive stores of thiamine. METHODExperiments were done on 10 subjects, of whom 6 were normal, 1 had hyperthyroidism and 3 were chronic diabetics. One of the latter also had carcinoma of the pancreas. In all the experiments thiamine was administered intramuscularly. In 3 of the normal individuals and in all the abnormal subjects thiamine was given daily for from 2 to 5 days in doses which ranged from 8.8 to 100 mgm. In some individuals the experiment was repeated with the same or a different dose. In the other 3 normal subjects the daily dose was increased every day or every 3 days over periods of from 9 to 37 days. In the first (B. A.) the d...

Genetic defects of thiamine transport and metabolism: A review of clinical phenotypes, genetics, and functional studies

“…TMP can also be recycled to free‐thiamine . Thiamine is also eliminated by feces (from gut microflora unrelated to the quantity of thiamine intake), sweat (5%‐15% of the thiamine intake) and breast milk (mostly as TMP, suggesting that folate carrier‐1 could be responsible for this excretion) …”

Biomarkers for In Vivo Assessment of Transporter Function

“…Under physiologic conditions and without thiamine supplementation, elimination of thiamine is mainly extrarenal. Upon thiamine supplementation resulting in increased plasma concentrations, extrarenal elimination may become saturated, and renal excretion may become the principal path of elimination (Alexander et al, 1946;Weber et al, 1990). In addition to free glomerular filtration, which may be assumed due to low molecular weight and absence of protein binding (Weber et al, 1990), both extensive tubular secretion and reabsorption processes may occur.…”

Mitochondrial transport and metabolism of the vitamin B‐derived cofactors thiamine pyrophosphate, coenzyme A,FADandNAD+, and related diseases: A review

“…Excess thiamine from intestinal absorption and cell secretion (9-18 days turnover time) is eliminated from circulation mainly through urine by glomerular filtration and in minor quantities in faeces and sweat in the form of free thiamine, ThMP, ThPP or more than 20 different degradation intermediates. 75,86,87 Once imported into the cytoplasm of animal cells, thiamine is transformed into ThPP by thiamine pyrophosphokinase (TPK1, thiamine pyrophosphotransferase or thiamine diphosphokinase) by transfer of a pyrophosphate from ATP onto thiamine (Figure 2). 88 Most probably cell-imported ThMP is converted into free thiamine and then to ThPP as in yeast and plants.…”