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Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans.| Autors: | Ana C Calvo, Angel L Pey, Ming Ying, Curtis M Loer, Aurora Martinez | | Idioma: | ENG. | | Data: | 7-5-2008 | | Revista: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(1530-6860)
| | Lliurament: | FASEB J. 6 May 2008 |
Abstract:
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In humans, liver phenylalanine hydroxylase (PAH) has an established catabolic function, and mutations in PAH cause phenylketonuria, a genetic disease characterized by neurological damage, if not treated. To obtain novel evolutionary insights and information on molecular mechanisms operating in phenylketonuria, we investigated PAH in the nematode Caenorhabditis elegans (cePAH), where the enzyme is coded by the pah-1 gene, expressed in the hypodermis. CePAH presents similar molecular and kinetic properties to human PAH [S0.5(L-Phe) approximately 150 microM; Km for tetrahydrobiopterin (BH4) approximately 35 microM and comparable Vmax], but cePAH is devoid of positive cooperativity for L-Phe, an important regulatory mechanism of mammalian PAH that protects the nervous system from excess L-Phe. Pah-1 knockout worms show no obvious neurological defects, but in combination with a second cuticle synthesis mutation, they display serious cuticle abnormalities. We found that pah-1 knockouts lack a yellow-orange pigment in the cuticle, identified as melanin by spectroscopic techniques, and which is detected in C. elegans for the first time. Pah-1 mutants show stimulation of superoxide dismutase activity, suggesting that cuticle melanin functions as oxygen radical scavenger. Our results uncover both an important anabolic function of PAH and the change in regulation of the enzyme along evolution.-Calvo, A. C., Pey, A. L., Ying, M., Loer, C. M., Martinez, A. Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans.
| | Copyright: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
*Department of Biomedicine, University of Bergen, Bergen, Norway; andDepartment of Biology, University of San Diego, San Diego, California, USA. | | Full text: | | | | |
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Articles d'altres especialitats: Pediatria, Medicina Interna, Bioquímica Clínica, Rehabilitacio, Cirurgia Toràcica, Oncologia, Oto-rino-laringologia (O.R.L.), Psicologia, Anatomia Patològica, Cardiologia, Medicina Intensiva, Cirurgia Plàstica, Estètica i Reparadora |
