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Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], ino...

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Published in:	The Journal of clinical investigation 1995-04, Vol.95 (4), p.1440-1445
Main Authors:	Whyte, M P, Landt, M, Ryan, L M, Mulivor, R A, Henthorn, P S, Fedde, K N, Mahuren, J D, Coburn, S P
Format:	Article
Language:	English
Subjects:	Alkaline Phosphatase - metabolism Diphosphates - metabolism Ethanolamines - metabolism Female Heterozygote Humans Hypophosphatasia - enzymology Hypophosphatasia - genetics Isoenzymes - metabolism Placenta - enzymology Pregnancy - physiology Prospective Studies Pyridoxal Phosphate - metabolism Substrate Specificity
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creator	Whyte, M P Landt, M Ryan, L M Mulivor, R A Henthorn, P S Fedde, K N Mahuren, J D Coburn, S P
description	Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.
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Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy</title><source>Open Access: PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Whyte, M P ; Landt, M ; Ryan, L M ; Mulivor, R A ; Henthorn, P S ; Fedde, K N ; Mahuren, J D ; Coburn, S P</creator><creatorcontrib>Whyte, M P ; Landt, M ; Ryan, L M ; Mulivor, R A ; Henthorn, P S ; Fedde, K N ; Mahuren, J D ; Coburn, S P</creatorcontrib><description>Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. 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Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.</description><subject>Alkaline Phosphatase - metabolism</subject><subject>Diphosphates - metabolism</subject><subject>Ethanolamines - metabolism</subject><subject>Female</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Hypophosphatasia - enzymology</subject><subject>Hypophosphatasia - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Placenta - enzymology</subject><subject>Pregnancy - physiology</subject><subject>Prospective Studies</subject><subject>Pyridoxal Phosphate - metabolism</subject><subject>Substrate Specificity</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNpVUs1u1DAQthCobAsHHgDJJ1AlUuwkjh0kDtWKn6JKHIBzNHEmGxfHDnaCSB-Y58DVbhc4jeXvbzT6CHnG2QXnMn99o02aipcPyIYLoTKVF-oh2TCW86yWhXpMTmO8YYyXpShPyImUrCpLuSG_L-13sMYhnQYfpwFmiPiGThY0uhksBdfR2cS4YOa8ixNq0xtNTfTobtcRIx3WLni73t5beJwHcN7CmGxfUeN82IFLmmkN_j4lAXfO6ct0_lfKES-zI3ZBvyxtnEN6UtB6GRcLs_EueVENIRgMkfo-JU_-79oGqPYhoJ4j7ZZg3I5OAXcOnF6fkEc92IhPD_OMfHv_7uv2Y3b9-cPV9vI606UUcyawLXTX59hpDlBzJSrN844xVFj2Ku8r1rVccVV2PBda1krrShS15LLFUtbFGXm7952Wdkwu6YYBbDMFM0JYGw-m-R9xZmh2_meT16LKRdK_OOiD_7FgnJvRRI3WgkO_xEbKnHHFqkQ83xN18DEG7I8ZnDV3nWg-ba_2nUjc5_8udWQeSlD8AZopvG8</recordid><startdate>19950401</startdate><enddate>19950401</enddate><creator>Whyte, M P</creator><creator>Landt, M</creator><creator>Ryan, L M</creator><creator>Mulivor, R A</creator><creator>Henthorn, P S</creator><creator>Fedde, K N</creator><creator>Mahuren, J D</creator><creator>Coburn, S P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950401</creationdate><title>Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy</title><author>Whyte, M P ; Landt, M ; Ryan, L M ; Mulivor, R A ; Henthorn, P S ; Fedde, K N ; Mahuren, J D ; Coburn, S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-5eb3cdf2edc1aa91856c12d00e8e4f82f60db18184d125c798cc6539717be4793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Alkaline Phosphatase - metabolism</topic><topic>Diphosphates - metabolism</topic><topic>Ethanolamines - metabolism</topic><topic>Female</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Hypophosphatasia - enzymology</topic><topic>Hypophosphatasia - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Placenta - enzymology</topic><topic>Pregnancy - physiology</topic><topic>Prospective Studies</topic><topic>Pyridoxal Phosphate - metabolism</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Whyte, M P</creatorcontrib><creatorcontrib>Landt, M</creatorcontrib><creatorcontrib>Ryan, L M</creatorcontrib><creatorcontrib>Mulivor, R A</creatorcontrib><creatorcontrib>Henthorn, P S</creatorcontrib><creatorcontrib>Fedde, K N</creatorcontrib><creatorcontrib>Mahuren, J D</creatorcontrib><creatorcontrib>Coburn, S P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Whyte, M P</au><au>Landt, M</au><au>Ryan, L M</au><au>Mulivor, R A</au><au>Henthorn, P S</au><au>Fedde, K N</au><au>Mahuren, J D</au><au>Coburn, S P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1995-04-01</date><risdate>1995</risdate><volume>95</volume><issue>4</issue><spage>1440</spage><epage>1445</epage><pages>1440-1445</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.</abstract><cop>United States</cop><pmid>7706447</pmid><doi>10.1172/jci117814</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects	Alkaline Phosphatase - metabolism Diphosphates - metabolism Ethanolamines - metabolism Female Heterozygote Humans Hypophosphatasia - enzymology Hypophosphatasia - genetics Isoenzymes - metabolism Placenta - enzymology Pregnancy - physiology Prospective Studies Pyridoxal Phosphate - metabolism Substrate Specificity
title	Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy
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