EC Number   |
General Information |
Reference |
|---|
    2.3.1.37 | evolution |
vertebrate genomes encode two highly conserved, but differentially expressed, ALAS genes, a housekeeping gene (ALAS1)5,6 and an erythroid-specific gene (ALAS2) |
735684 |
| 2.3.1.37 | malfunction |
enzyme mutations are associated with two different blood disorders, X-linked sideroblastic anemia and X-linked protoporphyria |
756091 |
| 2.3.1.37 | malfunction |
genetic mutations in the erythroid-specific isoform ALAS2 are associated with two inherited blood disorders, X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP). XLSA is caused by diminished ALAS2 activity leading to decreased ALA and heme syntheses and ultimately ineffective erythropoiesis, whereas XLPP results from gain-of-function ALAS2 mutations and consequent overproduction of protoporphyrin IX and increase in Zn2+-protoporphyrin levels |
756992 |
| 2.3.1.37 | malfunction |
mutation in Alas gena cause massive water loss. The cuticle of alas mutant larvae detaches from the epidermis and its basal region is frayed. Reduction of Alas function results in weakening of the extracellular dityrosines network in the cuticle. Alas activity, which initiates heme biosynthesis in the mitochondrion, might be needed for the formation of a dityrosine-based barrier that confers resistance to the internal hydrostatic pressure protecting both the cuticle from transcellular infiltration of body fluid and the animal from dehydration |
719402 |
| 2.3.1.37 | malfunction |
mutations in the C-terminal region of human erythroid-specific enzyme ALAS are associated with X-linked protoporphyria, a disease characterized by extreme photosensitivity, with elevated blood concentrations of free protoporphyrin IX and zinc protoporphyrin. The protein conformational transition step associated with product release is predominantly affected, because the mutations alter the microenvironment of the pyridoxal 5'-phosphate cofactor, which undergoes further and specific alterations upon succinyl-CoA binding. This results in enhanced activities of the XLPP mutant enzyme variants due to accelerations in the rate at which the product 5-aminolevulinate is released from the enzyme. The erythroid 5-aminolevulinate synthase mutations disrupt the conformational equilibrium. Molecular mechanism, overview |
735684 |
| 2.3.1.37 | malfunction |
mutations of the murine ALAS2 active site loop result in increased production of protoporphyrin IX, the precursor for heme. Generation of protoporphyrin IX is a crucial component in the widely used photodynamic therapies of cancer and other dysplasias. ALAS2 variants that cause high levels of protoporphyrin IX accumulation provide a means of targeted, and potentially enhanced, photosensitization. ALAS2-induced protoporphyrin IX accumulation followed by light exposure combined with paclitaxel treatment causes cell death |
737145 |
| 2.3.1.37 | malfunction |
X-linked protoporphyria is a erythropoietic porphyria due to gain-of-function mutations in the erythroid-specific aminolevulinate synthase gene (ALAS2). Two exon 11 small deletions, c.1699_1670DELTAAT and c.1706_1709DELTAAGTG (DELTAAGTG), that prematurely truncate or elongate the ALAS2 polypeptide, are reported to increase enzymatic activity 20 to 40fold, causing the erythroid accumulation of protoporphyrins, cutaneous photosensitivity and liver disease |
736819 |
| 2.3.1.37 | metabolism |
5-aminolevulinate synthase catalyzes the first committed step of heme biosynthesis in animals |
737145 |
| 2.3.1.37 | metabolism |
5-aminolevulinate synthase catalyzes the initial step of mammalian heme biosynthesis |
736491 |
| 2.3.1.37 | metabolism |
5-aminolevulinate synthase catalyzs the initial step of mammalian heme biosynthesis |
736116, 736454 |
