Aminolevulinic acid synthase (ALA synthase, ALAS, or delta-aminolevulinic acid synthase) is an enzyme (EC 2.3.1.37) that catalyzes the synthesis of δ-aminolevulinic acid (ALA) the first common precursor in the biosynthesis of all tetrapyrroles such as hemes, cobalamins and chlorophylls.[1]
The reaction is as follows:
succinyl-CoA + glycine δ-aminolevulinic acid + CoA + CO2
This enzyme is expressed in all non-plant eukaryotes and the α-class of proteobacteria and the reaction it catalyses is sometimes referred to as the Shemin pathway for ALA formation.[2] Other organisms produce ALA through a three enzyme pathway known as the C5 pathway. ALA is synthesized through the condensation of glycine and succinyl-CoA. In humans, transcription of ALA synthase is tightly controlled by the presence of Fe2+-binding elements, to prevent accumulation of porphyrin intermediates in the absence of iron. There are two forms of ALA synthase in the body. One form is expressed in red blood cell precursor cells (ALAS2), whereas the other (ALAS1) is ubiquitously expressed throughout the body. The red blood cell form is coded by a gene on chromosome X, whereas the other form is coded by a gene on chromosome 3.
The disease X-linked sideroblastic anemia is caused by mutations in the ALA synthase gene on chromosome X, whereas no diseases are known to be caused by mutations in the other gene. Gain of function mutations in the erythroid specific ALA synthase gene have been shown recently to cause a previously unknown form of porphyria known as X-linked-dominant protoporphyria.
^Hunter, Gregory A.; Ferreira, Gloria C. (November 2011). "Molecular enzymology of 5-Aminolevulinate synthase, the gatekeeper of heme biosynthesis". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1814 (11): 1467–1473. doi:10.1016/j.bbapap.2010.12.015. PMC 3090494. PMID 21215825.
^Shemin, David; Rittenberg, D (June 18, 1945). "The utilization of glycine for the synthesis of a porphyrin". Journal of Biological Chemistry. 159: 567–568.
and 28 Related for: Aminolevulinic acid synthase information
Aminolevulinicacidsynthase (ALA synthase, ALAS, or delta-aminolevulinicacidsynthase) is an enzyme (EC 2.3.1.37) that catalyzes the synthesis of δ-aminolevulinic...
δ-Aminolevulinicacid (also dALA, δ-ALA, 5ALA or 5-aminolevulinicacid), an endogenous non-proteinogenic amino acid, is the first compound in the porphyrin...
Aminolevulinicacid dehydratase deficiency porphyria (also known as "Doss porphyria", "plumboporphyria", or "ADP") is an extremely rare autosomal recessive...
chlorophyll depends on aminolevulinicacidsynthase, a PLP-dependent enzyme that uses succinyl-CoA and glycine to generate aminolevulinicacid, a chlorophyll...
Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ALAS1 gene. ALAS1 is an aminolevulinicacidsynthase. Delta-aminolevulinate...
Pyridoxal phosphate (a derivative of pyridoxine) is required for δ-aminolevulinicacidsynthase, the enzyme responsible for the rate-limiting step in heme synthesis...
complementary therapy for obesity. β-lipoic acid is a thiosulfinate of α-lipoic acidAminolevulinicacid "Lipoic Acid". Pubmed. NCBI. Retrieved October 18,...
Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene. ALAS2 is an aminolevulinicacidsynthase. The product...
in erythrocytes. Screening for FECH mutation on one allele or aminolevulinicacidsynthase 2 gain-of-function mutation in selected family members may be...
Givlaari is an siRNA drug that downregulates the expression of aminolevulinicacidsynthase 1 (ALAS1), a liver enzyme involved in an early step in heme production...
Soybean Root Nodules: I. On the Role of Bacteroid δ-AminolevulinicAcidSynthase and δ-AminolevulinicAcid Dehydrase in the Synthesis of the Heme of Leghemoglobin"...
Root Nodules: I. On the Role of Bacteroid delta-AminolevulinicAcidSynthase and delta-AminolevulinicAcid Dehydrase in the Synthesis of the Heme of Leghemoglobin"...
received EMA approval. Givosiran is an siRNA that breaks down aminolevulinicacidsynthase 1 (ALAS1) mRNA in the liver. Breaking down ALAS1 mRNA prevents...
dominant erythropoietic protoporphyria", associated with ALAS2 (aminolevulinicacidsynthase), has also been described. X-linked dominant erythropoietic protoporphyria...
heme and siroheme. The initial steps incorporate glutamic acid into 5-aminolevulinicacid (ALA); two molecules of ALA are then reduced to porphobilinogen...
eukaryotes, δ-aminolevulinicacid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA by the enzyme ALA synthase. Glycine provides...
iron-responsive element in murine and human erythroid delta-aminolevulinicacidsynthase mRNA". The EMBO Journal. 10 (7): 1903–1909. doi:10.1002/j.1460-2075...
"Estimation and application of biological variation of urinary delta-aminolevulinicacid and porphobilinogen in healthy individuals and in patients with acute...
Tretinoin, also known as all-trans retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it...
in structure to the metabolite that they interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites...
succinylacetone has been shown to decrease heme concentrations by inhibiting δ-aminolevulinicacid in murine erythroleukemia cells. The primary structure of heme-sequestering...
formation of δ-aminolevulinicacid (δ-ALA, 5-ALA or dALA) by the reaction of the amino acid glycine with succinyl-CoA from the citric acid cycle. In plants...
Vorinostat (rINN), also known as suberoylanilide hydroxamic acid (suberoyl+anilide+hydroxamic acid abbreviated as SAHA), is a member of a larger class of compounds...
Many steps are involved in converting aminolevulinicacid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it is used by...
Global Information
