Disease relevance of Slc25a20

• CAC mutants, in which one or more Cys residues had been replaced with Ser, were overexpressed in Escherichia coli and reconstituted into liposomes [1].
• The effect of hyperthyroidism on fatty acid oxidation and on carnitine-acylcarnitine translocase activity in rat heart mitochondria has been studied [2].
• The effect of hypothyroidism on fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid composition in rat heart mitochondria has been examined [3].

High impact information on Slc25a20

• Pan-1 and Pan-2 bind to the consensus sequence CAC/GCTGT/C, the CACCTGTC motif, which is present in transcriptional control elements of several genes [4].
• Both the in vivo and in vitro assays are affected by mutagenesis of nucleotides adjacent to the CAC [5].
• Nine HCCs contained a transition from adenine to guanine in the second base of codon 231 (CAC to CGC), which resulted in a histidine to arginine amino acid substitution; 4 HCCs contained a nonmiscoding transition from cytosine to thymidine in the third base of codon 294 (TGC to TGT; cysteine to cysteine) [6].
• The effect of SH oxidizing, cross-linking, and coordinating reagents was evaluated on the carnitine/carnitine exchange catalyzed by the recombinant reconstituted CAC proteins [1].
• However, whether their site of action is at the level of CPT I (outer membrane), CPT II (inner membrane), carnitine-acylcarnitine translocase (CACT, inner membrane), or some combination of these elements has never been resolved [7].

Biological context of Slc25a20

• The methylation of C-A is very low in the trinucleotides ACA and CAC, the other C-A containing trinucleotides in DNA are much better methylacceptors [8].
• The tandem repeat and its adjacent region consisted of a similar motif of CAC/TCC/AC/T [9].
• The cellular weakening or cytoxic consequences of CAC are intertwined in the most fundamental sense with energy intake, production, storage, and mobilization [10].
• Four groups of male Sprague-Dawley rats were used: CAC (24, control for acclimated), HAC (24, heat acclimated), TCAC (3, telemetry implanted control for acclimation), and THAC (3, telemetry implanted, heat acclimated) [11].
• The impact of CAC on the HPA axis to increase GCs makes this energy regulatory hormone along with pancreatic hormones a potential major player in the site-specific organ pathologies associated with CAC [10].

Anatomical context of Slc25a20

• On the basis of the values of internal and external transport affinities (K(m)) for carnitine and of their comparison with those measured in mitochondria, the recombinant CAC is oriented unidirectionally in the liposomes, right side out compared to mitochondria [12].
• Characterization of carnitine acylcarnitine translocase system of heart mitochondria [13].
• Enhancement of mitochondrial carnitine and carnitine acylcarnitine translocase-mediated transport of fatty acids into liver mitochondria under ketogenic conditions [14].
• A high-abundance protein of identical molecular size as the mitochondrial CAC that is immunoreactive with an anti-peptide antibody raised against a linear epitope of mitochondrial CAC is present in peroxisomes but not in microsomes [15].
• We interpret these data as evidence against a major role for an increase in the pH of hepatocyte lysosomes in CAC-induced phospholipidosis [16].

Associations of Slc25a20 with chemical compounds

• The proximity of the Cys residues present in the mitochondrial rat carnitine/acylcarnitine carrier (CAC) primary structure was studied by using site-directed mutagenesis in combination with chemical modification [1].
• Substitution of Cys-136 with Ser caused a nearly complete loss of sensitivity of the CAC to N-ethylmaleimide, (2-aminoethyl)methanethiosulfonate hydrobromide (MTSES), and other hydrophilic SH reagents but not to the very hydrophobic N-phenylmaleimide [12].
• Some of the known inhibitors of pyruvate transport inhibited the activity of carnitine-acylcarnitine translocase [17].
• This new approach has permitted the import of long chain acylcarnitine to be followed unambiguously; the results have confirmed that the carnitine acylcarnitine translocase is indeed involved in this import which also proceeds by a mole to mole exchange-diffusion against internal carnitine [18].
• The exchange of external carnitine and acylcarnitines for intramitochondrial carnitine was also inhibited by mersalyl and 1 mM mersalyl proved suitable for the inhibitor-stop assay of carnitine acylcarnitine translocase [13].

Other interactions of Slc25a20

• The mitochondrial carnitine palmitoyltransferase (CPT) system is composed of two proteins, CPT-I and -II, which, together with carnitine acylcarnitine translocase, are involved in the transport of fatty acids into the mitochondrial matrix for beta-oxidation [19].
• The carnitine acylcarnitine translocase activity is unlikely to be shared by one of the carnitine acyltransferases because the mersalyl inhibition of carnitine palmitoyltransferase and carnitine acetyltransferase was noncompetitivcase [13].
• We speculate that ALCAR may operate through interference with organic cation transporters such as OCTN2 and/or carnitine-acylcarnitine translocase (CACT), based partly on the above findings and on semi-empirical electronic similarity calculations on ALCAR, MPP+, and two other substrates for these transporters [20].

Analytical, diagnostic and therapeutic context of Slc25a20

• Gel mobility-shift assays demonstrate that the transcriptionally active 68-kDa fragment of the sterol regulatory element (SRE-1)-binding protein assays (SREBP-1) binds to an oligonucleotide containing the wild-type sequence but not to an oligonucleotide in which the CAC has been mutated [5].

References