Disease relevance of SLC25A20

• Indeed, all the described effects were completely overcome by CACT neo-expression by recombinant adenovirus vector or by addition of acetyl-carnitine to cultures [1].
• CACT deficiency is a life-threatening, recessively inherited disorder of lipid beta-oxidation which manifests in early infancy with hypoketotic hypoglycemia, cardiomyopathy, liver failure, and muscle weakness [2].
• The deleterious effect of the p.Arg133Trp substitution was demonstrated by measuring CACT activity upon expression of the normal and the mutant protein in E. coli and functional reconstitution into liposomes [2].
• Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis [3].
• To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002) [4].

Psychiatry related information on SLC25A20

• BACKGROUND: The goal was to investigate the relation of alcohol consumption to the presence of calcified atherosclerotic plaque in the coronary arteries (CAC) and aorta [5].

High impact information on SLC25A20

• Instead of an inverted repeat (CANNTG), the target for all known bHLH-ZIP proteins, SRE-1 contains a direct repeat of CAC [6].
• Brief report: a deficiency of carnitine-acylcarnitine translocase in the inner mitochondrial membrane [7].
• Genes encoding the CAF-I subunits (collectively referred to as CAC genes) are not essential for cell viability [8].
• Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts [9].
• Sequence analysis of amplified fragments from one patient revealed a single base substitution in exon 8, codon 448 from CGC (arginine) to CAC (histidine) [10].

Chemical compound and disease context of SLC25A20

• One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC) [4].
• The mutation of the cell line was a missense mutation from GAC (asparagine) to CAC (histidine) at codon 281, which was different from the G-to-T transversion of codon 249 that is frequently found in adult hepatocellular carcinomas (HCCs) [11].
• On the basis of recent studies using a human tumor pancreatic cancer (PC) xenograft in nude mice, a Phase I clinical trial of cisplatin, high-dose cytosine arabinoside (Ara-C), and caffeine (CAC) was performed in patients with advanced incurable PC [12].
• Conduction disorders and atrial tachycardias were observed in patients with defects of long-chain fatty acid transport across the inner mitochondrial membrane (carnitine palmitoyl transferase type II deficiency and carnitine acylcarnitine translocase deficiency) and in patients with trifunctional protein deficiency [13].
• Metabolic consequences of a defective CACT are hypoketotic hypoglycaemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and an abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines [14].

Biological context of SLC25A20

• We cloned and sequenced the human CAC cDNA, which has an open reading frame of 903 nucleotides [15].
• To probe the effect of CACT down-expression on lipid metabolism in muscle, human myocytes were stably transfected with CACT-antisense construct [1].
• All the introns except one are located at the level of the sequences coding for the extramembranous loops of CACT [16].
• We have designed a series of intronic oligonucleotide primers for amplifying each of the CACT exons together with their flanking intronic sequences, in segments well suited to detect mutations that would affect splicing of mRNA as well as the coding sequence itself [16].
• Assignment of the carnitine/acylcarnitine translocase gene (CACT) to human chromosome band 3p21.31 by in situ hybridization [17].

Anatomical context of SLC25A20

• The carnitine-acylcarnitine carrier (CAC) catalyzes the translocation of long-chain fatty acids across the inner mitochondrial membrane [15].
• The carnitine/acylcarnitine translocase (CACT) transports acylcarnitines into mitochondria in exchange for free carnitine and it is, therefore, essential for the fatty acid beta-oxidation pathway [16].
• CACT activity was totally deficient in cultured skin fibroblasts from all three patients [18].
• We describe the cellular and molecular biologic studies of the erythrocyte pyruvate kinase (PK) deficiency of the Amish deme in Pennsylvania. Nucleotide sequencing of the patient's PK gene showed a point mutation, CGC to CAC, corresponding to no [19].
• Introduction: This analysis studied the association of spine volumetric BMD (vBMD) with aortic (AC) and coronary artery (CAC) calcification in middle-aged women and evaluated whether such associations were independent of age and shared risk factors between osteoporosis and cardiovascular disease (CVD) or explained by endogenous estradiol levels [20].

Associations of SLC25A20 with chemical compounds

• Import of acylcarnitine into mitochondrial matrix through carnitine/acylcarnitine-translocase (CACT) is fundamental for lipid catabolism [1].
• Thus, in our experimental model the modulation of CACT expression has consequences for CPT 1 activity, while the biologic effects of acetyl-carnitine are not associated with a generic supply of energy compounds but to the anaplerotic property of the molecule [1].
• Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion [4].
• Structural features at the extra adenosine bulge sites in DNA duplexes have been elucidated from an NMR analysis of two-dimensional through space and through bond connectivities in the self-complementary d(C-C-G-G-A-A-T-T-C-A-C-G-G) (CAC 13-mer) and d(C-C-G-A-G-A-A-T-T-C-C-G-G) (GAG 13-mer) duplexes in aqueous solution [21].
• Estradiol did not influence this association. vBMD was related to high CAC in unadjusted (OR = 1.35; 95% CI, 1.08-1.70) but not adjusted models [20].

Other interactions of SLC25A20

• Control by [acetyl-CoA]/[CoASH] may also be significant, but it is probably via export of acyl groups by carnitine acylcarnitine translocase and CPT II rather than via accumulation of 3-ketoacyl-CoA esters [22].

Analytical, diagnostic and therapeutic context of SLC25A20

• Sequence analysis of the CACT gene (SLC25A20) disclosed five novel mutations and three previously reported mutations [2].
• Northern blot studies revealed different expression levels of CAC in various human tissues [15].
• Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant [4].
• The main outcome measures were CAC and AC, measured by electron beam tomography [23].
• Serum phenytoin concentrations, total and free, measured by two homogeneous enzyme immunoassays (EMIT, CAC) were reported to be within the therapeutic range, yet the patient experienced seizures [24].

References