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Difference between revisions of "Calvo 2008 FASEB J"

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{{Publication
{{Publication
|title=Calvo AC, Pey AL, Ying M, Loer CM, Martinez A (2008) Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans. FASEB J 22: 3046-3058
|title=Calvo AC, Pey AL, Ying M, Loer CM, Martinez A (2008) Anabolic function of phenylalanine hydroxylase in ''Caenorhabditis elegans''. FASEB J 22: 3046-3058
|info=[http://www.ncbi.nlm.nih.gov/pubmed/18460651 PMID: 18460651]
|info=[http://www.ncbi.nlm.nih.gov/pubmed/18460651 PMID: 18460651]
|authors=Calvo AC, Pey AL, Ying M, Loer CM, Martinez A
|authors=Calvo AC, Pey AL, Ying M, Loer CM, Martinez A
|year=2008
|year=2008
|journal=FASEB J
|journal=FASEB J
|abstract=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 [S(0.5)(L-Phe) approximately 150 microM; K(m) for tetrahydrobiopterin (BH(4)) approximately 35 microM and comparable V<sub>max</sub>], 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.
|abstract=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 [S(0.5)(L-Phe) approximately 150 microM; ''K''(m) for tetrahydrobiopterin (BH(4)) approximately 35 microM and comparable ''V''<sub>max</sub>], 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.
|keywords=Phenylketonuria, Melanin, cuticle, Oxygen radical scavenging, Tetrahydrobiopterin
|keywords=Phenylketonuria, Melanin, cuticle, Oxygen radical scavenging, Tetrahydrobiopterin
|discipline=Biomedicine
|discipline=Biomedicine

Revision as of 21:50, 22 June 2013

Publications in the MiPMap
Calvo AC, Pey AL, Ying M, Loer CM, Martinez A (2008) Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans. FASEB J 22: 3046-3058

Β» PMID: 18460651

Calvo AC, Pey AL, Ying M, Loer CM, Martinez A (2008) FASEB J

Abstract: 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 [S(0.5)(L-Phe) approximately 150 microM; K(m) for tetrahydrobiopterin (BH(4)) 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. β€’ Keywords: Phenylketonuria, Melanin, cuticle, Oxygen radical scavenging, Tetrahydrobiopterin


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Organism: Caenorhabditis elegans 

Preparation: Enzyme 



HRR: Oxygraph-2k 

worm