Research Topics
Genomes and Genes | P A WatkinsSummaryAffiliation: Kennedy Krieger Institute Country: USA Publications
Research Grants
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Publications
Human and great ape red blood cells differ in plasmalogen levels and compositionAnn B Moser
Hugo W Moser Research Institute at Kennedy Krieger, and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lipids Health Dis 10:101. 2011..Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease...- Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functionsPaul A Watkins
Department ofNeurology, Johns Hopkins University School of Medicine, Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA
BMC Physiol 10:19. 2010..Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism... - Disruption of a yeast very-long-chain acyl-CoA synthetase gene simulates the cellular phenotype of X-linked adrenoleukodystrophyP A Watkins
Kennedy Krieger Institute and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Cell Biochem Biophys 32:333-7. 2000..Characterization of the gene(s) responsible for the residual peroxisomal VLCS activity may suggest new therapeutic approaches in X-ALD... - Human very long-chain acyl-CoA synthetase and two human homologs: initial characterization and relationship to fatty acid transport proteinP A Watkins
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Prostaglandins Leukot Essent Fatty Acids 60:323-8. 1999..Elucidation of the biochemical functions of all VLCS/FATP family members should provide new insights into cellular fatty acid metabolism... - Brain uptake and utilization of fatty acids: applications to peroxisomal biogenesis diseasesP A Watkins
Kennedy Krieger Institute, Baltimore, MD 21205, USA
J Mol Neurosci 16:87-92; discussion 151-7. 2001..In addition to assessing the current state of knowledge, areas requiring additional investigation were identified and recommendations for future research were made. A brief overview of the invited talks is presented here... - Disruption of the Saccharomyces cerevisiae FAT1 gene decreases very long-chain fatty acyl-CoA synthetase activity and elevates intracellular very long-chain fatty acid concentrationsP A Watkins
Kennedy Krieger Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 273:18210-9. 1998..These studies suggest that the FAT1 gene product has VLCS activity that is essential for normal cellular very long-chain fatty acid homeostasis... - Very-long-chain acyl-CoA synthetasesPaul A Watkins
Kennedy Krieger Institute, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 283:1773-7. 2008 - Roundtable discussion of session 4: fatty acids and lipids in brain disordersPaul A Watkins
Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA
J Mol Neurosci 33:120-4. 2007 - Roundtable discussion of session 3: eicosanoids in brain functionPaul A Watkins
Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA
J Mol Neurosci 33:100-4. 2007 - Roundtable discussion of session 2: lipoproteins and polyunsaturated fatty acidsPaul A Watkins
Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA
J Mol Neurosci 33:74-9. 2007 - Roundtable discussion of session 1: mechanisms of lipid uptake and transport in the brainPaul A Watkins
Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA
J Mol Neurosci 33:45-50. 2007 - Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genomePaul A Watkins
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Lipid Res 48:2736-50. 2007..Knowing the full complement of ACS genes in the human genome will facilitate future studies to characterize their specific biological functions... - Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloning and characterization of a second enzymatically active proteinS J Steinberg
Kennedy Krieger Institute and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Mol Genet Metab 68:32-42. 1999..Thus, the primary role of hVLCS-H2 is likely to be in fatty acid elongation or complex lipid synthesis rather than in degradation... - The human liver-specific homolog of very long-chain acyl-CoA synthetase is cholate:CoA ligaseS J Steinberg
Kennedy Krieger Institute and the Departments of Neurology and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 275:15605-8. 2000..Our results are consistent with a role for hVLCS-H2 in the re-activation and re-conjugation of bile acids entering liver from the enterohepatic circulation rather than in de novo bile acid synthesis... - Very long-chain acyl-CoA synthetases. Human "bubblegum" represents a new family of proteins capable of activating very long-chain fatty acidsS J Steinberg
Kennedy Krieger Institute and Departments of Neurology and Pediatrics and the Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 275:35162-9. 2000..Because hsBG is expressed in brain but previously described VLCSs were not highly expressed in this organ, hsBG may play a central role in brain VLCFA metabolism and myelinogenesis... - Peroxisomal straight-chain Acyl-CoA oxidase and D-bifunctional protein are essential for the retroconversion step in docosahexaenoic acid synthesisH M Su
Department of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 276:38115-20. 2001..Our data are consistent with the retroconversion hypothesis and demonstrate that peroxisomal beta-oxidation enzymes acyl-CoA oxidase and D-bifunctional protein are essential for this process in human skin fibroblasts... - Altered expression of ALDP in X-linked adrenoleukodystrophyP A Watkins
Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Am J Hum Genet 57:292-301. 1995..Furthermore, the study of female relatives of immunonegative ALD probands may aid in the assessment of heterozygote status... - Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteinsL T Braiterman
Kennedy Krieger Research Institute, 707 North Broadway, Baltimore, MD 21205, USA
Hum Mol Genet 7:239-47. 1998..Thus it is likely that complex protein interactions are involved in the function and biogenesis of peroxisomal membranes that may contribute to disease heterogeneity... - Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophyM C McGuinness
Kennedy Krieger Institute and Departments of Neurology, Baltimore, Maryland 21205, USA
Mol Cell Biol 23:744-53. 2003..In support of this hypothesis, mitochondrial structural abnormalities were observed in adrenal cortical cells of ALD mice... - Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to branched-chain fatty acid metabolismS J Steinberg
Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
Biochem Biophys Res Commun 257:615-21. 1999..This orientation, coupled with the observation that hVLCS activates branched-chain fatty acids, suggests that hVLCS could play a role in the intraperoxisomal reactivation of pristanic acid produced via alpha-oxidation of phytanic acid... - Peroxisomal activation of long- and very long-chain fatty acids in the yeast Pichia pastorisJ E Kalish
Kennedy Krieger Research Institute, Baltimore, MD 21205
Biochem Biophys Res Commun 206:335-40. 1995..Thus, we conclude that VLCS is a peroxisomal enzyme in P. pastoris and this organism may serve as an excellent model system to investigate the molecular basis of XALD... - A mouse model for X-linked adrenoleukodystrophyJ F Lu
Department of Biology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 94:9366-71. 1997..We conclude that X-ALD mice exhibit biochemical defects equivalent to those found in human X-ALD and thus provide an experimental system for testing therapeutic intervention... - Identification of PAHX, a Refsum disease geneS J Mihalik
Kennedy Krieger Institute, Baltimore, Maryland, USA
Nat Genet 17:185-9. 1997..We find that both Refsum disease patients examined are homozygous for inactivating mutations in PAHX, demonstrating that mutations in PAHX can cause Refsum disease... - A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblastsS J Steinberg
Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland 21205, USA
J Inherit Metab Dis 32:109-19. 2009..Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver... - X-linked adrenoleukodystrophy: genes, mutations, and phenotypesK D Smith
The Kennedy Krieger Institute and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Neurochem Res 24:521-35. 1999..Finally, we discuss variable expression of the peroxisomal ABC proteins and ALDP independent VLCS in relation to the variable clinical presentations of X-ALD... - Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screeningL Bezman
Department of Neurology, Kennedy Krieger Institute and the Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Ann Neurol 49:512-7. 2001..Identification of heterozygotes provides the opportunity for disease prevention through genetic counseling. Diagnostic tests should be offered to all at-risk relatives of X-ALD patients and should include members of the extended family... - Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficienciesP A Watkins
Kennedy Krieger Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Ann Neurol 38:472-7. 1995..Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal beta-oxidation enzymes is possible... - Mouse very long-chain Acyl-CoA synthetase 3/fatty acid transport protein 3 catalyzes fatty acid activation but not fatty acid transport in MA-10 cellsZhengtong Pei
Kennedy Krieger Research Institute and Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 279:54454-62. 2004..These studies cast doubt on the designation of ACSVL3 as a fatty acid transport protein... - Peroxisomal bifunctional enzyme deficiencyP A Watkins
Kennedy Institute of Handicapped Children, Baltimore, Maryland 21205
J Clin Invest 83:771-7. 1989..It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone... - Mutational analysis of patients with X-linked adrenoleukodystrophyF Kok
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Hum Mutat 6:104-15. 1995..There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD... - The fatty acid transport protein (FATP) family: very long chain acyl-CoA synthetases or solute carriers?Zhenzhen Jia
Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205, USA
J Mol Neurosci 33:25-31. 2007..We conclude that, in the cell lines studied, endogenous FATP4 does not function to translocate FA across the plasma membrane... - Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA synthetase in skin fibroblastsZhenzhen Jia
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 707 N Broadway, Baltimore, MD 21205, USA
J Biol Chem 282:20573-83. 2007..FATP4-deficient cells also contained abnormal neutral lipid droplets. These additional defects indicate that metabolic abnormalities in these cells are not limited to very long chain fatty acids... - The second member of the human and murine bubblegum family is a testis- and brainstem-specific acyl-CoA synthetaseZhengtong Pei
Kennedy Krieger Institute and Department of Neurology and The Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 281:6632-41. 2006.... - X-linked adrenoleukodystrophy: role of very long-chain acyl-CoA synthetasesZhenzhen Jia
Institute for Genetic Medicine, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Mol Genet Metab 83:117-27. 2004..However, BG1 depletion in Neuro2a cells using RNA interference did not decrease incorporation of labeled VLCFA into cholesterol esters. We conclude that the role, if any, of ACSVL1 and BG1 in X-ALD biochemical pathology is indirect... - A very long-chain acyl-CoA synthetase-deficient mouse and its relevance to X-linked adrenoleukodystrophyAnn K Heinzer
The Kennedy Krieger Institute, Baltimore, MD 21205, USA
Hum Mol Genet 12:1145-54. 2003.... - The acyl-CoA synthetase "bubblegum" (lipidosin): further characterization and role in neuronal fatty acid beta-oxidationZhengtong Pei
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, 707 N Broadway, Baltimore, MD 21205, USA
J Biol Chem 278:47070-8. 2003..mBG1 appears to play a minor role in very long-chain fatty acid activation in these cells, indicating that other acyl-CoA synthetases are necessary for very long-chain fatty acid metabolism in Neuro2a cells... - Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver diseaseZhiping Li
The Johns Hopkins University, Baltimore, MD 21205, USA
Hepatology 37:343-50. 2003..In conclusion, these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions... - Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesityLisa M Davis
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Neuroendocrinology 89:152-62. 2009.... - Mouse models and genetic modifiers in X-linked adrenoleukodystrophyAnn K Heinzer
The Kennedy Krieger Institute, The Johns Hopkins School of Medicine, 707 North Broadway, Baltimore, MD, 21205, USA
Adv Exp Med Biol 544:75-93. 2003 - Acyl-CoA synthetase VL3 knockdown inhibits human glioma cell proliferation and tumorigenicityZhengtong Pei
Hugo W Moser Research Institute at Kennedy Krieger and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Cancer Res 69:9175-82. 2009..These studies show that ACSVL3 maintains oncogenic properties of malignant glioma cells via a mechanism that involves, in part, the regulation of Akt function... - Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recyclingStephanie J Mihalik
Kennedy Krieger Institute and the Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 277:24771-9. 2002..Results of in situ hybridization, topographic orientation, and inhibition studies are consistent with the proposed roles of these enzymes in bile acid metabolism... - Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophyAnn K Heinzer
Kennedy Krieger Institute, The Department of Pediatrics, The Johns Hopkins University, Baltimore, Maryland 21205, USA
J Biol Chem 277:28765-73. 2002..These observations imply that ALDP is not necessary for the proper expression or localization of Vlcs protein, and the control of VLCFA levels does not depend on the direct interaction of Vlcs and ALDP... - Brain uptake and utilization of fatty acids, lipids & lipoproteins: recommendations for future researchRobert Katz
Omega 3 Research Institute, Inc, 16700 Sioux Lane, Gaithersburg, MD 20878, USA
J Mol Neurosci 33:146-50. 2007..12) The relationship between LC-PUFA, stroke, and AD should be clarified, and neurogenetic metabolic diseases that could benefit from supplementation with omega3 LC-PUFA such as DHA should be identified... - Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4Katrin Milger
Department of Gastroenterology, Im Neuenheimer Feld 345, University of Heidelberg, 69120 Heidelberg, Germany
J Cell Sci 119:4678-88. 2006..We propose that the enzyme FATP4 drives fatty acid uptake indirectly by esterification. It is not a transporter protein involved in fatty acid translocation at the plasma membrane... - Comparative biochemical studies of the murine fatty acid transport proteins (FATP) expressed in yeastConcetta C DiRusso
Ordway Research Institute, Center for Metabolic Disease, Albany, New York 12208, USA
J Biol Chem 280:16829-37. 2005..These data support the conclusion that the different mmFATP isoforms play unique roles in fatty acid trafficking, including the transport of exogenous long-chain fatty acids... - Brain uptake and utilization of fatty acids, lipids and lipoproteins: application to neurological disordersJames A Hamilton
Boston University School of Medicine, Boston, MA, USA
J Mol Neurosci 33:2-11. 2007..In this article, we will provide an overview of the topics discussed in these sessions... - Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disordersDeyanira Corzo
Division of Genetics, The Children s Hospital, Boston, Massachusetts, USA
Am J Hum Genet 70:1520-31. 2002..The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED.. - Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene familyDouglas G Mashek
Departments of Nutrition and Pediatrics, University of North Carolina, Chapel Hill, NC 27599, USA
J Lipid Res 45:1958-61. 2004..Splice variants of ACSL3, -4, -5, and -6 are cataloged. Suggestions for naming other family members and for the nonmammalian acyl-CoA synthetases are made...
Research Grants
- XALD--ROLE OF VERY LONG CHAIN FATTY ACYL COA SYNTHETASESPaul Watkins; Fiscal Year: 2002..abstract_text> ..
- Acyl-CoA synthetase ACSVL3 in Malignant Glioma: Metabolism and Oncogenic CellularPaul Watkins; Fiscal Year: 2009..Results of these studies will provide a critical assessment of the mechanism by which this enzyme contributes to the malignant phenotype, and the potential therapeutic benefit of targeting this enzyme in glioma. ..
- XALD: Role of Very Long Chain Fatty Acyl-CoA SynthetasesPaul Watkins; Fiscal Year: 2006..Furthermore, they will facilitate elucidation of the role of enzymes belonging to the VLACS or BG families in XALD. ..
- Brain Uptake and Utilization of Fatty Acids and LipidsPaul Watkins; Fiscal Year: 2004..Mol. Neurosci., which has committed to publish the proceedings of the proposed meeting. ..
- Acyl-CoA synthetase ACSVL3 in Malignant Glioma: Metabolism and Oncogenic CellularPaul A Watkins; Fiscal Year: 2010..Results of these studies will provide a critical assessment of the mechanism by which this enzyme contributes to the malignant phenotype, and the potential therapeutic benefit of targeting this enzyme in glioma. ..