R. N. Gupta

Biosynthesis of the piperidine nucleus: The occurrence of two pathways from lysine

Abstract 2- 3 H,6- 14 C- dl -Lysine was administered to the intact rat, to intact bean plants ( Phaseolus vulgaris ) and to excised shoots of Sedum acre . Pipecolic acid (IV), which was isolated from each of these tissues, contained 14 C but was free of tritium. Since incorporation of label from 6- 3 H,6- 14 C- dl -lysine into pipecolic acid had previously been shown 1 to take place specifically and to occur without change in 3 H: 14 C ratio in each of these systems, the evidence is now complete that conversion of lysine (I) into pipecolic acid (IV) proceeds via ϵ-amino-α-ketocaproic acid (II) and Δ 1 -piperideine-2-carboxylic acid (III) and not via α-aminoadipic-δ-semialdehyde (VI) and Δ 1 -piperideine-6-carboxylic acid (V). In S. acre , 2- 3 H,6- 14 C- dl -lysine was incorporated into sedamine (X) without change in 3 H: 14 C ratio. It follows that ϵ-amino-α-ketocaproic acid (II) cannot be an intermediate in the biosynthesis of sedamine from lysine, as had been previously suggested. Specific conversion of 6- 3 H,6- 14 C- dl -lysine into sedamine without change in 3 H: 14 C ratio had been demonstrated earlier. This and other evidence had been interpreted to show that α-aminoadipic-δ-semialdehyde (VI) is not an intermediate on the route from lysine to sedamine and other piperidine alkaloids. An alternative pathway, which invokes neither ϵ-amino-α-ketocaproic acid nor α-aminoadipic-δ-semialdehyde as intermediate, is now suggested.

Influence of renal clearance on peripheral homovanillic acid measurements in healthy subjects and schizophrenic patients

In order to investigate the effect of renal clearance on plasma homovanillic acid (HVA) concentrations, we examined plasma concentration and urinary excretion of HVA and creatinine per 4 h over 24 h in eight male schizophrenic patients and eight healthy male subjects. Renal clearances of HVA and of creatinine were determined per 4 h period. No significant differences were found between groups in the total 24 h excretion of either HVA or creatinine. Although differences between groups in plasma HVA concentrations and urinary HVA excretion per 4 h did not reach statistical significance, the renal clearance of HVA was significantly lower in the patient group than in the control group. There was no difference between groups in creatinine clearance. Diurnal changes were seen in the renal clearance of HVA and creatinine in both groups. Renal HVA clearance decreased from 23.00-07.00 h, with a coincident decrease in urinary HVA excretion and an increase in plasma HVA concentration. We provide evidence that renal clearance is an important determinant of plasma HVA concentration, and should be considered when interpreting plasma HVA data.

Concentration response relationships of amiodarone and desethylamiodarone

Twelve patients with frequent ventricular premature depolarizations (VPDs) received amiodarone, 600 mg/day, for up to 8 weeks. On days 0, 1, 4, 8, 15, 22, 36, and 57 of treatment, 24-hour ambulatory ECGs were obtained, and multiple blood samples were taken for determination of amiodarone and desethylamiodarone plasma concentrations. All patients had at least 75% suppression of VPDs. The mean duration of therapy before the onset of antiarrhythmic effect was 13.2 days (range 1 to 36 days). Trough amiodarone and desethylamiodarone plasma concentrations at the time of onset of antiarrhythmic effect were 0.86 +/- 0.48 mg/L and 0.23 +/- 0.15 mg/L, respectively. Sixty-seven percent of patients responded at amiodarone concentrations below 1.0 mg/L. For each patient there was a progressive decrease in frequency of VPDs as both amiodarone and desethylamiodarone concentrations increased. Regression modeling indicated that both amiodarone and desethylamiodarone plasma concentrations explained significant variability in the frequency of VPDs, and amiodarone and desethylamiodarone plasma concentrations were highly correlated with each other. There was a trend for desethylamiodarone to explain more variability in frequency of VPDs than amiodarone.

Biosynthesis of N-methylpelletierine ☆

Abstract The biosynthesis of N -methylpelletierine (VII) was studied in excised shoots of Sedum sarmentosum . Consistent with classical biogenetic concepts, the piperidine nucleus of the alkaloid is generated from lysine, which is incorporated by way of nonsymmetrical intermediates, very probably ϵ-amino-α-ketocaproic acid and Δ 1 -piperideine-2-carboxylic acid. The propanone side-chain originates from acetate. Direct incorporation into the side-chain of an intact three-carbon unit derived from acetoacetate could not be demonstrated.

Biosynthesis of the Lycopodium alkaloids: the origin of cernuine

Even though lysine and pelletierine (I) serve as precursors of the Lycopodium alkaloid, cernuine (IV), the alkaloid is not a modified dimer of pelletierine, as might have been anticipated on the basis of structural relations, since only one pelletierine unit is incorporated.