Редактирование: FAH

Fumarylacetoacetase (EC 3.7.1.2) (FAA) (Beta-diketonase) (Fumarylacetoacetate hydrolase)

==Publications==

{{medline-entry
|title=Oxaloacetate decarboxylase [[FAH]]D1 - a new regulator of mitochondrial function and senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30055189
|abstract=[[FAH]]D1, a member of the [[FAH]] superfamily of enzymes, was identified in a proteomic screen for mitochondrial proteins with differential expression in young versus senescent human endothelial cells. [[FAH]]D1 acts as oxaloacetate decarboxylase, and recent observations suggest that [[FAH]]D1 plays an important role in regulating mitochondrial function. Thus, mutation of the nematode homolog, fahd-1, impairs mitochondrial function in Caenorhabditis elegans. When [[FAH]]D1 gene expression was silenced in human cells, activity of the mitochondrial electron transport (ETC) system was reduced and the cells entered premature senescence-like growth arrest. These findings suggest a model where [[FAH]]D1 regulates mitochondrial function and in consequence senescence. These findings are discussed here in the context of a new concept where senescence is divided into deep senescence and less severe forms of senescence. We propose that genetic inactivation of [[FAH]]D1 in human cells induces a specific form of cellular senescence, which we term senescence light and discuss it in the context of mitochondrial dysfunction associated senescence (MiDAS) described by others. Together these findings suggest the existence of a continuum of cellular senescence phenotypes, which may be at least in part reversible.
|mesh-terms=* Animals
* Caenorhabditis elegans
* Cellular Senescence
* Endothelial Cells
* Humans
* Hydrolases
* Mitochondria
|keywords=* FAHD1
* Mitochondria
* Oxaloacetate (OAA)
* Oxaloacetate decarboxylase (ODx)
* Senescence
* Senescence light
|full-text-url=https://sci-hub.do/10.1016/j.mad.2018.07.007
}}
{{medline-entry
|title=Depletion of oxaloacetate decarboxylase [[FAH]]D1 inhibits mitochondrial electron transport and induces cellular senescence in human endothelial cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28286170
|abstract=In this study we report the identification of [[FAH]] domain containing protein 1 ([[FAH]]D1), a recently described member of the fumarylacetoacetate hydrolase ([[FAH]]) superfamily of metabolic enzymes, as a novel player in the regulation of cellular senescence. [[FAH]]D1 was found in a proteomic screen searching for mitochondrial proteins, which are differentially regulated in mitochondria from young and senescent human endothelial cells, and subsequently identified as oxaloacetate decarboxylase. We report here that depletion of [[FAH]]D1 from human endothelial cells inhibited mitochondrial energy metabolism and subsequently induced premature senescence. Whereas senescence induced by [[FAH]]D1 depletion was not associated with DNA damage, we noted a reduction of mitochondrial ATP-coupled respiration associated with upregulation of the cdk inhibitor p21. These results indicate that [[FAH]]D1 is required for mitochondrial function in human cells and provide additional support to the growing evidence that mitochondrial dysfunction can induce cellular senescence by metabolic alterations independent of the DNA damage response pathway.
|mesh-terms=* Cell Line
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p21
* DNA Damage
* Electron Transport
* Endothelial Cells
* Energy Metabolism
* Humans
* Hydrolases
* Mitochondria
|keywords=* DNA damage
* Energy metabolism
* FAHD1
* Mitochondria
* Oxaloacetate decarboxylase
* Premature senescence
|full-text-url=https://sci-hub.do/10.1016/j.exger.2017.03.004
}}
{{medline-entry
|title=Associations between toe grip strength and hallux valgus, toe curl ability, and foot arch height in Japanese adults aged 20 to 79 years: a cross-sectional study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25972928
|abstract=The associations between toe grip strength (TGS) and foot structure are not well known, although foot structure is inferred to affect TGS. This study investigated the associations between TGS and hallux valgus angle (HVA), toe curl ability, and foot arch height ([[FAH]]). This study analysed 227, 20 to 79-year-old, community-dwelling participants. TGS, HVA formed by the first metatarsal bone and the proximal phalanx of the hallux, toe curl ability (percentage) calculated as (foot length-flexed foot length)/foot length, and [[FAH]] (percentage) calculated as navicular height/truncated foot length were measured. To elucidate associations between TGS and foot structure, a correlation analysis and stepwise multivariate linear regression analyses were performed, based on the participant's sex. Pearson's correlation coefficients for TGS with age, height, weight, HVA, toe curl ability, and [[FAH]] were also calculated. In the stepwise, multivariate linear regression analyses, the independent variable was TGS and the dependent variables were those that significantly correlated with TGS, as shown by the Pearson's correlation coefficients. The significance level was set at 5%. According to the Pearson's correlation coefficients, in men, TGS was significantly correlated with age, height, toe curl ability, and [[FAH]]. According to the stepwise multiple regression analysis, TGS correlated with age and toe curl ability (adjusted R(2)=0.22). In women, TGS was significantly correlated with age, height, and toe curl ability (adjusted R(2)=0.40). TGS was associated with toe curl ability in both men and women. However, TGS was not associated with HVA and [[FAH]] in men or women. The results of this study may lead to the development of effective interventions to improve TGS. However, factors other than structure of the foot require more detailed investigation to clarify the factors contributing to TGS.

|keywords=* Aging
* Foot
* Hallux valgus
* Muscle strength
* Range of motion
* Sex
* Toes
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430032
}}
{{medline-entry
|title=The Caenorhabditis elegans K10C2.4 gene encodes a member of the fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of type I tyrosinemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18227072
|abstract=In eukaryotes and many bacteria, tyrosine is degraded to produce energy via a five-step tyrosine degradation pathway. Mutations affecting the tyrosine degradation pathway are also of medical importance as mutations affecting enzymes in the pathway are responsible for type I, type II, and type III tyrosinemia. The most severe of these is type I tyrosinemia, which is caused by mutations affecting the last enzyme in the pathway, fumarylacetoacetate hydrolase ([[FAH]]). So far, tyrosine degradation in the nematode Caenorhabditis elegans has not been studied; however, genes predicted to encode enzymes in this pathway have been identified in several microarray, proteomic, and RNA interference (RNAi) screens as perhaps being involved in aging and the control of protein folding. We sought to identify and characterize the genes in the worm tyrosine degradation pathway as an initial step in understanding these findings. Here we describe the characterization of the K10C2.4, which encodes a homolog of [[FAH]]. RNAi directed against K10C2.4 produces a lethal phenotype consisting of death in young adulthood, extensive damage to the intestine, impaired fertility, and activation of oxidative stress and endoplasmic stress response pathways. This phenotype is due to alterations in tyrosine metabolism as increases in dietary tyrosine enhance it, and inhibition of upstream enzymes in tyrosine degradation with RNAi or genetic mutations reduces the phenotype. We also use our model to identify genes that suppress the damage produced by K10C2.4 RNAi in a pilot genetic screen. Our results establish worms as a model for the study of type I tyrosinemia.
|mesh-terms=* Aging
* Animals
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* Disease Models, Animal
* Fertility
* Hydrolases
* Intestines
* Mutation
* Oxidative Stress
* Phenotype
* Protein Folding
* RNA Interference
* Tyrosine
* Tyrosinemias

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431024
}}