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Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes
Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of bio...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253636/ https://www.ncbi.nlm.nih.gov/pubmed/32508887 http://dx.doi.org/10.3389/fgene.2020.00510 |
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author | Cronan, John E. |
author_facet | Cronan, John E. |
author_sort | Cronan, John E. |
collection | PubMed |
description | Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of biochemical analysis at the enzyme level. An exception was the LIPT1 protein for which a perplexing property had been reported, a ligase lacking the ability to activate its substrate. This led to several models, some contradictory, to accommodate the role of LIPT1 protein activity in explaining the phenotypes of the afflicted neonatal patients. Recent evidence indicates that this LIPT1 protein activity is a misleading evolutionary artifact and that the physiological role of LIPT1 is in transfer of lipoic acid moieties from one protein to another. This and other new biochemical data now define a straightforward pathway that fully explains each of the human disorders specific to the assembly of lipoic acid on its cognate enzyme proteins. |
format | Online Article Text |
id | pubmed-7253636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72536362020-06-05 Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes Cronan, John E. Front Genet Genetics Three human mitochondrial diseases that directly affect lipoic acid metabolism result from heterozygous missense and nonsense mutations in the LIAS, LIPT1, and LIPT2 genes. However, the functions of the proteins encoded by these genes in lipoic acid metabolism remained uncertain due to a lack of biochemical analysis at the enzyme level. An exception was the LIPT1 protein for which a perplexing property had been reported, a ligase lacking the ability to activate its substrate. This led to several models, some contradictory, to accommodate the role of LIPT1 protein activity in explaining the phenotypes of the afflicted neonatal patients. Recent evidence indicates that this LIPT1 protein activity is a misleading evolutionary artifact and that the physiological role of LIPT1 is in transfer of lipoic acid moieties from one protein to another. This and other new biochemical data now define a straightforward pathway that fully explains each of the human disorders specific to the assembly of lipoic acid on its cognate enzyme proteins. Frontiers Media S.A. 2020-05-21 /pmc/articles/PMC7253636/ /pubmed/32508887 http://dx.doi.org/10.3389/fgene.2020.00510 Text en Copyright © 2020 Cronan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Cronan, John E. Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title | Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title_full | Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title_fullStr | Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title_full_unstemmed | Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title_short | Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes |
title_sort | progress in the enzymology of the mitochondrial diseases of lipoic acid requiring enzymes |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253636/ https://www.ncbi.nlm.nih.gov/pubmed/32508887 http://dx.doi.org/10.3389/fgene.2020.00510 |
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