Marlaire, Simon
Van Schaftingen, Emile
[UCL]
Veiga da Cunha, Maria
[UCL]
Glutarate, a side-product in the metabolism of tryptophan and lysine, is metabolized by conversion to glutaryl-CoA by a transferase using succinyl-CoA as a coenzyme donor. The enzyme catalyzing this conversion has not been formally identified. However, a benign form of glutaric aciduria (glutaric aciduria type III) is due to mutations in C7orf10, a putative member of the coenzyme A transferase class III family. In the present work, we show that recombinant human C7orf10 catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. C7orf10 could use many dicarboxylic acids as CoA acceptors, the best ones being glutarate, succinate, adipate, and 3-hydroxymethylglutarate. Confocal microscopy analysis of CHO cells transfected with a C7orf10-GFP fusion protein indicated that C7orf10 is a mitochondrial protein, in agreement with the presence of a predicted mitochondrial propeptide at its N-terminus. The effect of a missense mutation (p.Arg336Trp) found in the homozygous state in several patients with glutaric aciduria type III and present in the general population at a low frequency was also investigated. The p.Arg336Trp mutation led to the production of insoluble and inactive C7orf10 both in Escherichia coli and in HEK293T cells. These findings indicate that C7orf10 is implicated in the metabolism of glutarate, but possibly also of longer dicarboxylic acids. Homologues of this enzyme are found in numerous bacterial operons comprising also a putative glutaryl-CoA dehydrogenase, indicating that an enzyme with similar specificity exists in prokaryotes.
- Alfares A., Nunez L. D., Al-Thihli K., Mitchell J., Melancon S., Anastasio N., Ha K. C. H., Majewski J., Rosenblatt D. S., Braverman N., Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype, 10.1136/jmedgenet-2011-100230
- Amendt B A, Rhead W J, The multiple acyl-coenzyme A dehydrogenation disorders, glutaric aciduria type II and ethylmalonic-adipic aciduria. Mitochondrial fatty acid oxidation, acyl-coenzyme A dehydrogenase, and electron transfer flavoprotein activities in fibroblasts., 10.1172/jci112553
- Bennett M. J., Pollitt R. J., Goodman S. I., Hale D. E., Vamecq J., Atypical riboflavin-responsive glutaric aciduria, and deficient peroxisomal glutaryl-CoA oxidase activity: a new peroxisomal disorder, 10.1007/bf01800589
- Berthold Catrine L., Toyota Cory G., Richards Nigel G. J., Lindqvist Ylva, Reinvestigation of the Catalytic Mechanism of Formyl-CoA Transferase, a Class III CoA-transferase, 10.1074/jbc.m709353200
- Bonthron David T., Brady Nlcola, Donaldson lain A., Steinmann Beat, Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase), 10.1093/hmg/3.9.1627
- Bouteldja Nadia, Timson David J., The biochemical basis of hereditary fructose intolerance, 10.1007/s10545-010-9053-2
- Danhauser Katharina, Sauer Sven W., Haack Tobias B., Wieland Thomas, Staufner Christian, Graf Elisabeth, Zschocke Johannes, Strom Tim M., Traub Thorsten, Okun Jürgen G., Meitinger Thomas, Hoffmann Georg F., Prokisch Holger, Kölker Stefan, DHTKD1 Mutations Cause 2-Aminoadipic and 2-Oxoadipic Aciduria, 10.1016/j.ajhg.2012.10.006
- Deana R (1992) Substrate specificity of a dicarboxyl-CoA: dicarboxylic acid coenzyme A transferase from rat liver mitochondria. Biochem Int 26:767–773
- Emanuelsson Olof, Nielsen Henrik, Brunak Søren, von Heijne Gunnar, Predicting Subcellular Localization of Proteins Based on their N-terminal Amino Acid Sequence, 10.1006/jmbi.2000.3903
- FitzPatrick David R., Hill Alison, Tolmie John L., Thorburn David R., Christodoulou John, The Molecular Basis of Malonyl-CoA Decarboxylase Deficiency, 10.1086/302492
- Francesconi Maria Angela, Donella-Deana Arianna, Furlanetto Valerio, Cavallini Lucia, Palatini Pietro, Deana Renzo, Further purification and characterization of the succinyl-CoA:3-hydroxy-3-methylglutarate coenzyme A transferase from rat-liver mitochondria, 10.1016/0167-4838(89)90213-6
- Fu Zhuji, Wang Ming, Paschke Rosemary, Rao K. Sudhindra, Frerman Frank E., Kim Jung-Ja P., Crystal Structures of Human Glutaryl-CoA Dehydrogenase with and without an Alternate Substrate: Structural Bases of Dehydrogenation and Decarboxylation Reactions†,‡, 10.1021/bi049290c
- Goodman Stephen I., Stene Dan O., McCabe Edward R.B., Norenberg Michael D., Shikes Robert H., Stumpf David A., Blackburn Glen K., Glutaric acidemia type II: Clinical, biochemical, and morphologic considerations, 10.1016/s0022-3476(82)80525-8
- Goodman SI, Frerman FE (2001) Organic acidemias due to defects in lysine oxidation: 2-ketoadipic academia and glutaric academia. In: Scriver CR, Beaudet AL, Valle D, Childs B, Kinzler KW, Vogelstein B (eds). The metabolic and molecular bases of inherited disease, 8th edn. Chap. 95, pp 2195–2204. McGraw-Hill, New York
- Gregersen N., Kølvraa S., Rasmussen K., Christensen E., Brandt N. J., Ebbesen F., Hansen F. H., Biochemical studies in a patient with defects in the metabolism of acyl-CoA and sarcosine: Another possible case of glutaric aciduria type II, 10.1007/bf02312527
- Knerr I., Zschocke J., Trautmann U., Dorland L., de Koning T. J., Müller P., Christensen E., Trefz F. K., Wündisch G. F., Rascher W., Hoffmann G. F., 10.1023/a:1021207419125
- Kölker Stefan, Christensen Ernst, Leonard James V., Greenberg Cheryl R., Boneh Avihu, Burlina Alberto B., Burlina Alessandro P., Dixon Marjorie, Duran Marinus, García Cazorla Angels, Goodman Stephen I., Koeller David M., Kyllerman Mårten, Mühlhausen Chris, Müller Edith, Okun Jürgen G., Wilcken Bridget, Hoffmann Georg F., Burgard Peter, Diagnosis and management of glutaric aciduria type I – revised recommendations, 10.1007/s10545-011-9289-5
- Sloan Jennifer L, Johnston Jennifer J, Manoli Irini, Chandler Randy J, Krause Caitlin, Carrillo-Carrasco Nuria, Chandrasekaran Suma D, Sysol Justin R, O'Brien Kevin, Hauser Natalie S, Sapp Julie C, Dorward Heidi M, Huizing Marjan, Barshop Bruce A, Berry Susan A, James Philip M, Champaigne Neena L, de Lonlay Pascale, Valayannopoulos Vassilli, Geschwind Michael D, Gavrilov Dimitar K, Nyhan William L, Biesecker Leslie G, Venditti Charles P, Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria, 10.1038/ng.908
- Sherman Eric A., Strauss Kevin A., Tortorelli Silvia, Bennett Michael J., Knerr Ina, Morton D. Holmes, Puffenberger Erik G., Genetic Mapping of Glutaric Aciduria, Type 3, to Chromosome 7 and Identification of Mutations in C7orf10, 10.1016/j.ajhg.2008.09.018
- Swigoňová Zuzana, Mohsen Al-Walid, Vockley Jerry, Acyl-CoA Dehydrogenases: Dynamic History of Protein Family Evolution, 10.1007/s00239-009-9263-0
- Veiga-da-Cunha Maria, Hadi Farah, Balligand Thomas, Stroobant Vincent, Van Schaftingen Emile, Molecular Identification of Hydroxylysine Kinase and of Ammoniophospholyases Acting on 5-Phosphohydroxy-l-lysine and Phosphoethanolamine, 10.1074/jbc.m111.323485
- Veiga-da-Cunha M, Verhoeven-Duif NM, de Koning TJ, Duran M, Dorland B, Van Schaftingen E (2013) Mutations in the AGXT2L2 gene cause phosphohydroxylysinuria. J Inherit Metab Dis. 2012 Dec 14 Epub ahead of print
- Veiga-da-Cunha Maria, Tyteca Donatienne, Stroobant Vincent, Courtoy Pierre J., Opperdoes Fred R., Van Schaftingen Emile, Molecular Identification of NAT8 as the Enzyme That Acetylates CysteineS-Conjugates to Mercapturic Acids, 10.1074/jbc.m110.110924
- Verhoeven Nanda M., Huck Jojanneke H.J., Roos Birthe, Struys Eduard A., Salomons Gajja S., Douwes Adriaan C., van der Knaap Marjo S., Jakobs Cornelis, Transaldolase Deficiency: Liver Cirrhosis Associated with a New Inborn Error in the Pentose Phosphate Pathway, 10.1086/320108
- Wamelink Mirjam M.C., Struys Eduard A., Jansen Erwin E.W., Levtchenko Elena N., Zijlstra Fokje S.M., Engelke Udo, Blom Henk J., Jakobs Cornelis, Wevers Ron A., Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of theCARKLgene, 10.1002/humu.20685
- Wendel U., Bakkeren J., de Jong J., Bongaerts G., Glutaric aciduria mediated by gut bacteria, 10.1007/bf00710431
- Wiame Elsa, Tyteca Donatienne, Pierrot Nathalie, Collard François, Amyere Mustapha, Noel Gaëtane, Desmedt Jonathan, Nassogne Marie-Cécile, Vikkula Miikka, Octave Jean-Noël, Vincent Marie-Françoise, Courtoy Pierre J., Boltshauser Eugen, van Schaftingen Emile, Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia, 10.1042/bj20091024
Bibliographic reference |
Marlaire, Simon ; Van Schaftingen, Emile ; Veiga da Cunha, Maria. C7orf10 encodes succinate-hydroxymethylglutarate CoA-transferase, the enzyme that converts glutarate to glutaryl-CoA.. In: Journal of Inherited Metabolic Disease, Vol. 37, no. 1, p. 13-9 (2014) |
Permanent URL |
http://hdl.handle.net/2078.1/139951 |