Disease relevance of Alas2

• Heme administration causes inhibition of delta-aminolevulinate synthase (ALAS), best tested in the allylisopropylacetamide (AIA)-treated rat, a model for hepatic porphyrias [1].

High impact information on Alas2

• An alternate pathway for delta-aminolevulinic acid synthesis, in contrast to the condensation of succinate and glycine by delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] has been suggested [2].
• Translational inhibition by heme of the synthesis of hepatic delta-aminolevulinate synthase in a cell-free system [3].
• Incorporation of cytosol delta-aminolevulinate synthase of rat liver into the mitochondria in vitro [4].
• The size of the purified papain-resistant core catalytic domain of ALAS-E was estimated electrophoretically to be 49,000 Da [5].
• To obtain direct evidence for a unique ALAS-E, we have purified ALAS-E to homogeneity for the first time, from rat reticulocyte lysate [5].

Biological context of Alas2

• By combining the nucleotide sequence information of the cDNA and genomic clones, the rat ALAS-E precursor is predicted to be composed of 587 amino acids with a calculated molecular mass of 64,841 Da [5].

Anatomical context of Alas2

• Cobalt protoporphyrin inhibited the drug-induced increase of delta-aminolevulinate synthase as well as its transfer from the cytosol fraction to the mitochondria in rat liver in a similar way to protoheme [6].

Associations of Alas2 with chemical compounds

• The pH optimum (7.6) and apparent Km values for the substrates, glycine (6.5 mM) and succinyl-CoA (2 microM), were similar to those of the non-specific form of delta-aminolevulinate synthase (ALAS-N); but, in contrast to ALAS-N, the substrate inhibition by succinyl-CoA was not evident in ALAS-E [5].
• Effects of hemin on the synthesis and intracellular translocation of delta-aminolevulinate synthase in the liver of rats treated with 3,5-dicarbethoxy-1,4-dihydrocollidine [7].
• The observed regulatory effects of cobalt chloride with respect to the induction and the intracellular translocation of delta-aminolevulinate synthase may be mediated by cobalt protoporphyrin synthesized in vivo [6].

Analytical, diagnostic and therapeutic context of Alas2

• Northern blot and in situ hybridization analyses demonstrated that the non-specific ALAS (ALAS-N) mRNA is highly expressed in this tissue, whereas the erythroid-specific ALAS (ALAS-E) mRNA is not [8].

References