Literature summary for 2.3.1.37 extracted from

Fratz, E.J.; Hunter, G.A.; Ferreira, G.C.
Expression of murine 5-aminolevulinate synthase variants causes protoporphyrin IX accumulation and light-induced mammalian cell death (2014), PLoS ONE, 9, e93078.

Search for more literature for 2.3.1.37

Application

Application	Comment	Organism
medicine	delivery of stable and highly active ALAS2 variants has the potential to expand and improve upon current photodynamic therapies regimes	Mus musculus

Cloned(Commentary)

Cloned (Comment)	Organism
gene ALAS, recombinant expression in HeLa cells, stable expression of enzyme variants in K-562 cells	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
K313A	site-directed mutagenesis, inactive mutant	Mus musculus
additional information	generation of enzyme mutant with mutated mitochondrial presequences, at residues C11 C38, and C70, and a mutation in the active site loop Expression of the mutants in human cells causes significant cellular accumulation of protoporphyrin IX, particularly in the membrane. ALAS2 expression results in an increase in cell death in comparison to aminolevulinic acid treatment producing a similar amount of protoporphyrin IX. Supplementation of cell culture medium with glycine leads to increased protoporphyrin IX accumulation in Malas2-expressing HeLa cells	Mus musculus
R433K	site-directed mutagenesis, mALAS2 variant with a mutated presequence, the mutation results in an increase in activity to twice that of the wild-type enzyme, i.e. a 2fold increase in the kcat value and a 1.65 to 1.85fold enhancement in the specificity constants for glycine and succinyl-CoA over those of wild-type, mature mALAS2, 2.5fold increase in protoporphyrin IX accumulation in HeLa cells expressing the R433K precursor with a mutated presequence	Mus musculus
V423L/Y428R/P432E/R433I/G434N/E435Q/L437K	site-directed mutagenesis,	Mus musculus

Inhibitors

Inhibitors	Comment	Organism	Structure
heme	feedback inhibition of mitochondrial import	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Mus musculus	5739	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
succinyl-CoA + glycine	Mus musculus	-	5-aminolevulinate + CoA + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	P08680	gene alas2	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
succinyl-CoA + glycine	-	Mus musculus	5-aminolevulinate + CoA + CO2	-	?

Synonyms

Synonyms	Comment	Organism
5-aminolevulinate synthase	-	Mus musculus
ALAS	-	Mus musculus

Expression

Organism	Comment	Expression
Mus musculus	the enzyme is negatively regulated by heme at the level of mitochondrial import	down

General Information

General Information	Comment	Organism
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	Mus musculus
metabolism	5-aminolevulinate synthase catalyzes the first committed step of heme biosynthesis in animals	Mus musculus

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Release 2023.1 (January 2023)