The Antipyridoxine Effect of Penicillamine in Man*

Jaffe, Israeli A.; Altman, Kurt I.; Merryman, Parvin

doi:10.1172/jci105060

Cited by 104 publications

(31 citation statements)

References 20 publications

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“…Penicillamine causes inhibition of the kynurenine pathway and pyridoxine metabolism (2), the reduction of the activities of liver transaminases and liver cysteine desulfhydrase (3,4), the inhibition of collagen fibre crosslinking (5), and the inhibition in bone marrow of DNA, RNA, and protein synthesis (6). In all but the last of the toxic effects cited above, penicillamine is acting on an ubiquitous coenzyme called pyridoxal-5-phosphate.…”

Section: Introductionmentioning

confidence: 99%

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2R,4S-2-(2′-Methyl-3′-hydroxy-5′-hydroxymethylenepyridine-C4′)-5,5-dimethylthiazolidine-4-carboxylic acid, the product of the reaction of D-penicillamine and vitamin B6

Faggiani¹,

Howard-Lock²,

Lock³

et al. 1991

Can. J. Chem.

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R. FAGGIANI, H. E. HOWARD-LOCK, C. J. L. LOCK, and R. ORGIAS. Can. J. Chem. 69, 1 (1991).We have studied the reaction of both D-and L-penicillamine with pyridoxal hydrochloride and examined the products by single crystal X-ray diffraction. The structure of the title compound, A, formed by the reaction of D-penicillamine and pyridoxal was determined. Crystals are orthorhombic, P212121, with cell dimensions a = 9.507(5), b = 19.185(5), c = 7.766(2) a and Z = 4. The structure was solved by standard methods and refined to R = 0.088, R,, = 0.079 for 2433 independent reflections. A exists as a zwitterion, and bond lengths and angles are normal. In the solid state, A and the corresponding product obtained from L-penicillamine, B, have identical geometrical structure but are of opposite chirality; that is, D-penicillamine produces the 2R,4S diastereomer and L-penicillamine produces the 2S,4R diastereomer (with no S , S and R,R components). In solution, however, NMR spectra show the presence of both pairs of diastereomers (2R,4S and 2S,4S; 2S,4R and 2R,4R). In neutral or alkaline solution there appears to be a rapid epimerization at the thiazolidine carbon atom attached to the pyridoxal moiety. Features of the mass, 'H NMR, vibrational, and electronic spectra are also discussed. On a CtudiC la reaction des D-et L-~Cnicillamines avec le chlorhydrate du pyridoxal et on a examink la nature des produits obtenu: par diffraction des rayons-X par un cristal unique. On a dtterminC la structure du composC A mentionnC dans le titre et form6 par la rtaction de la D-ptnicillamine avec le pyridoxal. Les cristaux sont orthorhombiques, P212121, avec a = 9,507(5), identiques, mais de chiralitts oppostes; c'est-a-dire que la D-pCnicillamine conduit au diastCrCoisomkre 2R,4S alors que la L-~Cnicillamine conduit au diasttrCoisomkre 2S,4R (sans contamination par les composantes S,S ou R,R). Toutefois, en solution, les spectres RMN montrent qu'il existe deux paires de diastCrCoisomkres (2R,4S et 2S,4S; 2S,4R et 2R,4R). I1 semble que, en solutions neutres ou alcalines, il se produit une tpimkrisation rapide de I'atome de carbone de la thiazolidine qui est attache a la portion pyridoxal. On discute aussi des caracttristiques spectrales (masse, RMN du 'H, vibrationnels et Clectroniques) de ces produits.

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Section: Introductionmentioning

confidence: 99%

“…The principal derivatives of vitamin B6 are pyridoxal, pyridoxal-5-phosphate, pyridoxamine, and pyridoxine, all of which are interconvertible in vivo (2). The postulated targets of penicillamine are the aldehydes, pyridoxal and pyridoxal-5-phosphate.…”

Section: Introductionmentioning

confidence: 99%

2R,4S-2-(2′-Methyl-3′-hydroxy-5′-hydroxymethylenepyridine-C4′)-5,5-dimethylthiazolidine-4-carboxylic acid, the product of the reaction of D-penicillamine and vitamin B6

Faggiani¹,

Howard-Lock²,

Lock³

et al. 1991

Can. J. Chem.

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“…The abnormal excretion of the B6 activity is expected to cause a depletion of B6 in animal tissues. JAFFE et al (14) also showed previously that the administration of D-PeA to patients with rheumatoid arthritis resulted in an increase in urinary excretion of xanthurenic acid and kynurenine, which have been known as a param eter of B6 deficiency. It is therefore concluded that D-PeA, like L-isomer, caused a depletion of PLP which can be attributed to the gross excretions of PL-T and PL in the urine.…”

Section: Methodsmentioning

confidence: 83%

“…It was therefore suggested that only D-PeA be used in treatments of the disease described above. Subsequent studies, however, showed that D-PeA also was capable of pro ducing evidence of an antivitamin B6 effect in the rat (13) and in man (14), using the urinary excretion of xanthurenic acid as a parameter of B6 deficiency. TAKA HASHI and MATSUDA (15) also demonstrated that the administration of D-PeA to mice resulted in the decrease of PLP content in the brain which could be due to the formation of PLP-T, though the diminution of the PLP content was slight as compared to that of L-PeA.…”

Section: Discussionmentioning

confidence: 99%

Effects of penicillamine on distribution of B6 vitamers in rat urine.

Kajiwara

Matsuda

1978

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe antivitamin B6 effect of DL and D-penicillamine has been studied in rats. A considerable elevation in the urinary excretion of vitamin B6 activity (pyridoxal and its thiazolidine derivative) has been shown as a parameter of B6 antagonism. Both DL and D-penicillamine have been shown to have an antivitamin B6 effect in rats, although that induced by the DL-form is considerably greater, as would be expected from previous studies. We suggest that B6 supplementation should be included in any long term penicillamine therapy, regardless of the isomer that is employed.

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“…This fact has also been found in scleroderma patients without EMS [16. 19], Such abnormalities, which are in part reversible upon pyridoxine loading, might be due to a silent pyridoxine deficiency similar to that occuring in D-pcnicillaminc-or isoniazid-treated patients [28][29][30], Heavy /.-tryptophan intake might uncover such a deficiency in some patients.…”

Section: A Deficiency In Monoamine Oximentioning

confidence: 99%

<i>L</i>-Tryptophan-Induced Eosinophilia-Myalgia Syndrome

Mainetti¹,

Fathi

Saurat³

1991

Dermatology

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Abnormal metabolism of tryptophan is one of the possible aetiological factors in the L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). We studied the plasma levels of tryptophan and serotonin and the urinary excretion of kynurenine and 5-hydroxyin-doleacetic acid after oral intake of L-tryptophan in 1 subject with EMS and 2 healthy subjects. The test was repeated with concomitant administration of pyridoxine. In the patient there were elevated levels of plasma tryptophan during the loading and increased elimination of kynurenine in the urine both during and after the L-tryptophan test. During pyridoxine administration tryptophan levels and kynurenine elimination were much reduced, and kynurenine elimination was similar to that of controls. This study (i) confirms that an abnormal metabolism of L-tryptophan occurs in EMS patients and (ii) shows that this can be corrected by pyridoxine.

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The Antipyridoxine Effect of Penicillamine in Man*

Cited by 104 publications

References 20 publications

2R,4S-2-(2′-Methyl-3′-hydroxy-5′-hydroxymethylenepyridine-C4′)-5,5-dimethylthiazolidine-4-carboxylic acid, the product of the reaction of D-penicillamine and vitamin B6

2R,4S-2-(2′-Methyl-3′-hydroxy-5′-hydroxymethylenepyridine-C4′)-5,5-dimethylthiazolidine-4-carboxylic acid, the product of the reaction of D-penicillamine and vitamin B6

Effects of penicillamine on distribution of B6 vitamers in rat urine.

<i>L</i>-Tryptophan-Induced Eosinophilia-Myalgia Syndrome

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