A Hydrophilic Tetrahydro-β-Carboline in Human Urine

Abstract

A substance that exhibited a tryptophan-like fluorescence peak at 354 nm on excitation at 295 nm at neutral pH was isolated from human urine. This compound was determined by visible-light absorption spectroscopy, fluorescence spectroscopy, 1H and 13C NMR spectroscopies, and FAB-MS to be 1-(1',2',3',4',5'-pentahydroxypentyl)-1,2,3,4-tetrahydro-2-carboli ne-3- carboxylic acid. This compound, named tetrahydropentoxyline, is a new type of hydrophilic tetrahydro-beta-carboline, and its elution position was between those of 4-pyridoxic acid and kynurenic acid on C18 reversed-phase HPLC. The amount of tetrahydropentoxyline excreted in the urine of normal subjects [n = 21; age, 45 (SD 20) years] was about 5.2 (SD 1.0) mg per day.

Tryptophan glycoconjugates in food and human urine

“…The chemical shifts and coupling constants of compound 1 correspond to reported results [7], but the topological assignments of the "$C-NMR signals are different. In the "H-NMR spectrum of compound 1, the signal of the indole H-2 is absent, indicating that tryptophan is substituted at C-2 by the hexose moiety (indole H-1 was not observable owing to proton exchange in the applied solvents C#H $ O#H and #H # O).…”

“…This compound was proposed to have a tetrahydro-β-carboline structure, but the identity of the sugar part remained to be established [7]. As the occurrence of related tryptophan glycoconjugates in dietary sources has not yet been investigated, an exogenous origin for the tryptophan metabolite could not be excluded.…”

The diagnostic value of serum concentrations of 2-(α-mannopyranosyl)-l-tryptophan for normal renal function

“…The structure of MPT is illustrated in Figure 1. MPT is found in serum and cerebrospinal fluid [2]. Although its metabolism and physiologic role remain to be clarified, our previous report has shown that MPT clearance is almost identical to inulin clearance in experimental animals, indicating a similar renal handling of the two molecules [4].…”

“…Serum creatinine concentration is widely used for assessing renal function in the clinical setting, because of its speed and simplicity. However, as it is greatly influenced by muscle mass as well as renal function [1][2][3], the measurement of serum creatinine concentration can be prone to misinterpretation of the results in subjects with diminished muscle mass, such as the elderly, children, and females. Thus, the measurement of serum creatinine concentration may overestimate renal function in these populations.…”

“…We have previously reported that the serum concentration of MPT is an accurate measure of renal function even in subjects with diminished muscle mass and a better indicator of renal function than serum creatinine concentration [4]. MPT, isolated from human urine [2], is a stable substance with a molecular weight of 366 D. This substance has been demonstrated to be a tryptophan c-glycoside and to be characterized by a sugar moiety bound to the carbon [3]. The structure of MPT is illustrated in Figure 1.…”