Disease relevance of HACL1

• Very recently, a nontumorigenic liver epithelial cell line (HACL-1) with a finite life-span and expressing a number of hepatocyte-specific markers was established from a human hepatocellular adenoma in our laboratory [1].
• The effect of thiamine deficiency on 2-HPCL and alpha-oxidation has not been studied, nor have possible adverse effects of deficient alpha-oxidation been considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA) [2].

High impact information on HACL1

• Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids [3].
• To analyze the role of mutated p53 in the immortalization of human liver cells, we transfected HACL-1 cells with an expression vector containing a human p53 complementary DNA mutated at the third base of codon 249 and analyzed the consequences of this gene transfer on the growth properties of this cell line [1].
• One peptide, HIPDVITY, is encoded by squalene synthase, and the other one, QFADVIVLF, is encoded by 2-hydroxyphytanoyl-CoA lyase [4].
• The HACL-1 cells have a finite life span (i.e., they proliferate for a period of 2 months and then senesce), show cell-cell contact inhibition, do not grow in soft agar, are not tumorigenic when injected in nude mice, and possess a normal diploid karyotype [5].
• The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the alpha-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes [2].

Anatomical context of HACL1

• The subcellular localization of the enzymes involved has remained enigmatic, with the exception of phytanoyl-CoA hydroxylase and 2-hydroxyphytanoyl-CoA lyase which are both localized in peroxisomes [6].
• HPCL-purified CF sputum defensins were pure as judged by acid urea-PAGE and N-terminal sequencing, which revealed a mixture of defensins-1, -2 and -3 at ratios of approximately 4:2:1 [7].
• Metabolism of dextromethorphan in human liver microsomes: a rapid HPCL assay to monitor cytochrome P450 2D6 activity [8].

Associations of HACL1 with chemical compounds

• Concentrations of this steroid were then measured using radioimmunoassay upon which analysis of HPCL and gas chromatograms permitted the calculation of the individual pregnenolone ester contributions within the samples [9].
• Selected food items in edible form were analyzed for the coenzyme Q content by HPCL with UV-detection, and their contribution to the total intake calculated [10].
• We have studied the second step in the alpha-oxidation pathway, which involves conversion of 2-hydroxyphytanoyl-CoA to pristanal catalysed by 2-hydroxyphytanoyl-CoA lyase [11].
• METHODS: The Leiden mutation was measured by the method of polymerase chain reaction, the retinoid level in the patient's serum was measured by high liquid cromathografic method (HPCL) [12].

Other interactions of HACL1

• Phytanic acid alpha-oxidation in man: identification of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal enzyme with normal activity in Zellweger syndrome [13].

Analytical, diagnostic and therapeutic context of HACL1

• METHODS: 5HT (platelet rich plasma, platelet poor plasma, urine, HPLC with electrochemical detection) and 5HIAA (plasma, urine, HPCL with electrochemical detection) levels were evaluated in 14 conservatively treated (CT) and 12 hemodialysed (HD) patients with CRI and were compared to those of 60 healthy volunteers (HV) [14].
• Cell fractionation studies demonstrate that in rat liver 2-hydroxyphytanoyl-CoA lyase is localised in peroxisomes [11].

References