The effect of pyridoxine treatment of a homocystinuric
patient on the urinary excretion of some sulfur-containing amino acids was studied and the following results were obtained. As a result of pyridoxine treatment, urinary homocystine decreased to a fairly great extent, and its unusual metabolites S.(3-hydroxy-3-carboxyn- propylthio) homocysteine (HCPTHC) and S-C8-carboxyethylthio homocysteine (j3-CETHC) increased to some extent. But its oxidation product (homocysteic acid) showed a tendency to decrease slightly. Urinary methionine and cystine increased to some extent, but cysteinehomocysteine mixed disulfide showed no remarkable change.</p

Ikegami, T.

Kodama, H.

Oura, T.

Yao, K.

English

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Effect of pyridoxine treatment of a homocystinuric patient on the urinary excretion of some sulfur-containing amino acids

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 28, Issue 4 1974 Article 1AUGUST 1974Effect of pyridoxine treatment of ahomocystinuric patient on the urinaryexcretion of some sulfur-containing aminoacidsH. Kodama∗ T. Ikegami†K. Yao‡ T. Oura∗∗∗Okayama University,†Okayama University,‡Okayama University,∗∗Children’s Medical Center oj Osaka City,Copyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Effect of pyridoxine treatment of ahomocystinuric patient on the urinaryexcretion of some sulfur-containing aminoacids∗H. Kodama, T. Ikegami, K. Yao, and T. OuraAbstractThe effect of pyridoxine treatment of a homocystinuric patient on the urinary excretion ofsome sulfur-containing amino acids was studied and the following results were obtained. As aresult of pyridoxine treatment, urinary homocystine decreased to a fairly great extent, and itsunusual metabolites S.(3-hydroxy-3-carboxyn- propylthio) homocysteine (HCPTHC) and S-C8-carboxyethylthio homocysteine (j3-CETHC) increased to some extent. But its oxidation product(homocysteic acid) showed a tendency to decrease slightly. Urinary methionine and cystine in-creased to some extent, but cysteinehomocysteine mixed disulfide showed no remarkable change.∗PMID: 4280234 [PubMed - indexed for MEDLINE] Copyright c©OKAYAMA UNIVERSITYMEDICAL SCHOOLActa Med. Okayama 28, 243-246 (1974,EFFECT OF PYRIDOXINE TREATMENT OF A HOMO·CYSTINURIC PATIENT ON THE URINARY EXCRETIONOF SOME SULFUR·CONTAINING AMINO ACIDSH. KODAMA, T. IKEGAMI and K. YAODepartment of Biochemistry, Okayama University Medical School,Okayama, Japan (Director: Prof. S. Mizuhara)T.OURAChildren's Medical Center oj Osaka City, Osaka, JapanReceived for publication, January 19, 1974Abstract: The effect of pyridoxine treatment of a homocystinuricpatient on the urinary excretion of some sulfur-containing aminoacids was studied and the following results were obtained. As aresult of pyridoxine treatment, urinary homocystine decreased to afairly great extent, and its unusual metabolites S.(3-hydroxy-3-carboxy-n-propylthio) homocysteine (HCPTHC) and S-C8-carboxyethylthio)homocysteine (j3-CETHC) increased to some extent. But its oxidationproduct (homocysteic acid) showed a tendency to decrease slightly.Urinary methionine and cystine increased to some extent, but cysteine-homocysteine mixed disulfide showed no remarkable change.At least two types of homocystinuria have been recognized: one ispyridoxine-sensitive and the other fails to respond to pyridoxine treatment,and most of these investigations are concerned with the changes of methionine,homocystine and cystine in blood and urine. Recently, however, many un-usual sulfur-containing amino acids shown in Fig. 1 have been found in theurine of homocystinuric patient (1-4), so the studies of pyridoxine effect onthe urinary excretion of these unusual metabolites will be of great interest.Chemical terms and abbreviations of unusual sulfur-containing amino acidsare listed in Fig. 1.MATERIALS AND METHODSPyridoxine hydrochloride (200 mgjdl) was administered daily to a homo-cystinuric patient found in Osaka for two weeks from October 12 to 26 in 1972,and four urine samples were collected as follows: 1. Control urine before Betreatment (6.2liters), August 24-31; 2. Be Administration I in Table 1 (2.6liters), October 13-19; 3. Be Admimstration II (3.8 liters), October 20-26; 4.After Be Administration (3.9 liters), November 6-12.According to our usual method (5), two liters each of urine samples was atfirst divided into two fractions by using a column containing one liter of DiaionSK-l (H form, mesh 1(0), and so-called Fraction I (5) was further divided into2431Kodama et al.: Effect of pyridoxine treatment of a homocystinuric patient on theProduced by The Berkeley Electronic Press, 1974244 H. KODAMA, T. IKEGAMI, K. YAO and T. OURAFig. I. Unusual Metabolism of Homocysteine in HomocystinuricPatents./ ....-5.....-<><,-oo-COOH_ :=;;::::=:::::::::;=~::::=~Homocl"!~:--_:~l:::OO- COOH~ @",,5-\,,-COOH'~ CH-COOHHomorCyal'~~ i I® ~omoCYl"ine Sulfinic Acid I. I (!) Homocy.,.ic Acid Iy,'"ne@ CyS-S-CHz-CHz-COOHCyS-S-CHrCHz-CO-COOH- @ CYS-S-CHz-CHz-9H-COOH~ OH"li..d Di.ulfide'\. @ HcyS-S-CHz-COOHHcyS-S-CHz-CO-COOH - <U> HcyS-S-CH2-~H-COOHOH1. S-(p'-carboxyethylthio) homocysteine2. S-(3-hydroxy-3-carboxy-n-propylthio) homocysteine3. S-I,B-carboxyethyl) homocysteine4. S-(3-hydroxy-3-carboxy-n-propyl) homocysteine5. S-(1, 2-dicarboxyethyl) homocysteine8. S-(,B-carboxyethylthio) cysteine9. S-(3-hydroxy·3-carboxy-n-propylthio) cysteine10. S-(carboxymethylthio) homocysteineII. S-(2-hYdroxY-2-carboxyethYI thio) homocysteineAbbreviations,B-CETHCHCPTHC$-CEHCHCPHCDCEHC,B-CETCHCPTCCMTHCHCETHCTABLE I EFFECT OF PYRIDOXINE ADMINISTRATION ON THE EXCRETION OF SULFUR-CONTAINING AMINO ACIDS IN THE URINE OF A HOMOCYSTINURIC PATIENTBefore B6 Administration AfterI IIMethionine 82.0 129.0 210.0 490.0Homocystine 260.0 110.0 131. 0 157.0Mixed disulfide 337.0 233.0 345.8 281.8Cystine (Half) 49.3 44.0 143.0 89.0Homocysteic acid 6.72 6.21 4.86 2.20p-CETHC 0.30 0.95 1. 53 O. 74HCPTHC 5.17 22.10 15.40 26.50Values are expressed in f1 moles/literthree fractions by using a column containing 400 ml of Amberlite IRA-68 (ace-tate form, mesh 50). Fractions Ib and Ic thus obtained were combined andtransferred to a column containing 500 ml of Diaion SK-l (H form, mesh 1(0).The effluent and water washings were evaporated to dryness and used for thedetermination of homocysteic acid.2Acta Medica Okayama, Vol. 28 [1974], Iss. 4, Art. 1http://escholarship.lib.okayama-u.ac.jp/amo/vol28/iss4/1Effect of Pyridoxine Treatment on a Homocystinuric Patient 245After washing with water, the column was further washed with 2000 mlof 2 N HCI, 2000 ml of water, and then eluted with 1000 ml of 2 N NH 3 • Theammonia eluate containing fi-CETHC and HCPTHC was evaporated to dry-ness and analyzed on an automatic amino acid analyzer (Hitachi Model 034Liquid Chromatograph). Cystine, methionine, mixed disulfide and homo-cystine were analyzed directly on an amino acid analyzer after hydrolysis ofeach original urine without further fractionation.RESULTS AND DISCUSSIONResults of pyridoxine effect on the urinary excretion of several sulfur-containing amino acids are summarized in Table 1.The excretion of homocystine tends to decrease after pyridoxine treat-ment and its unusual metabolites CB-CETHC and HCPTHC) increase to someextent. It is well known that cysteine and also homocysteine react withpyridoxal to give thiazo1idine derivatives and the latter derivatives cannotparticipate directly in pyridoxal-catalyzed reactions (6). So the reducedexcretion of homocystine after Be treatment might be attributed to someextent to the formation of thiazolidine derivative. But it cannot be deniedthat pyridoxine treatment enhances the deamination of homocysteine or homo-cystine, because of the excretion of its degradation products (p-CETHC andHCPTHC) being increased.Decreasing tendency of urinary homocysteic acid may be due to thereduction of homocysteine in tissues. Even if the amount of mixed disulfideis taken into account, the amount of urinary homocystine still has a tendencyto decrease and that of cystine to increase. As described above, cysteine alsoreacts with pyridoxal to give a thiazolidine derivative. So the increasingtendency of cystine excretion after Be treatment is inexplicable at present.Even if the cystathionine synthase remaining in tissues of the patient is con-sidered to be activated by Be treatment, it is still incomprehensible whyurinary methionine tends to increase after Be treatment. At any rate, such apatient has not been encountered as yet.The other sulfur-containing amino acids listed in Table I could not bemeasured at this time, because of the repeated fractionations being requiredfor their determinations as reported in previous papers (1-4).REFERENCES1. KODAMA, H., MIZUHARA, S., HARAGUCHI, H. and HIROSAWA, M.: S-(1,2-dicarboxyethyl)homocysteine in the urine of homocystinuric patients. Physiol. Chern. Phys. 1, 600, 19692. KODAMA, H., OHMORJ, S., SUZUKI, M., MIZUHARA, S., OURA, T., ISSHIKI, G. and UEMURA,I.: Unusual sulfur-containing amino acids in the urine of homocystinuric patients: I.Physiol. Chern. Phys. 3, 81, 19713. KODAMA, H.: Unusual sulfur-containing amino acids in the urine of homocystinuric3Kodama et al.: Effect of pyridoxine treatment of a homocystinuric patient on theProduced by The Berkeley Electronic Press, 1974246 H. KODAMA, T. IKEGAMI, K. YAO and T. OURApatients: II. Physiol. Chern. Phys. 3, 159, 19714. OHMORI, S., KODAMA, H., IKEGAMI, T., MIZUHARA, S., OURA, T., ISSHIKI, G. and UEMURA,I.: Unusual sulfur-containing amino acids in the urine of homocystinuric patients: III.Physiol. Chern. Phys. 4, 286, 19725. KODAMA, H., OHMORI, S., SUZUKI, M. and MIZUHARA, S.: New sulfur-containing aminoacids in the urine of cystathioninuric patients: Supplementary data. Physiol. Chern. Phys.2, 287, 19706. ABBOTT, E. H. and MARTELL, A. E.: Pyridoxine and pyridoxal analogs: XIII. ]. Am. chern.Soc. 92, 1754, 19704Acta Medica Okayama, Vol. 28 [1974], Iss. 4, Art. 1http://escholarship.lib.okayama-u.ac.jp/amo/vol28/iss4/1

New sulfur-containing amino acids in the urine of cystathioninuric patients: Supplementary data.

Pyridoxine and pyridoxal analogs:

S-(1,2-dicarboxyethyl) homocysteine in the urine of homocystinuric patients.

Unusual sulfur-containing amino acids in the urine of homocystinuric Kodama et al.: Effect of pyridoxine treatment of a homocystinuric patient on the Produced by The Berkeley Electronic Press,

Unusual sulfur-containing amino acids in the urine of homocystinuric patients:

Effect of pyridoxine treatment of a homocystinuric patient on the urinary excretion of some sulfur-containing amino acids

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