2.3.1.37: 5-aminolevulinate synthase

This is an abbreviated version!
For detailed information about 5-aminolevulinate synthase, go to the full flat file.

Reaction

Synonyms

5-ALA synthase, 5-ALAS, 5-aminolevulinate synthase, 5-aminolevulinate synthetase, 5-aminolevulinic acid synthase, 5-aminolevulinic acid synthetase, ALA, ALA synthase, ALA synthetase, ALA-S, ALAS, ALAS2, alpha-aminolevulinic acid synthase, aminolevulinate synthase, aminolevulinate synthase 2, aminolevulinate synthetase, aminolevulinic acid synthase, aminolevulinic acid synthase 2, aminolevulinic acid synthetase, aminolevulinic synthetase, delta-ALAS, delta-aminolevulinate synthase, delta-aminolevulinate synthetase, delta-aminolevulinic acid synthase, delta-aminolevulinic acid synthase 2, delta-aminolevulinic acid synthetase, delta-aminolevulinic synthetase, erythroid 5-aminolevulinate synthase, erythroid-specific 5-aminolevulinate synthase, Hem1, hemA, HemT, mALAS-2, sigma-aminolevulinate synthase, synthase, aminolevulinate, synthetase, aminolevulinate

ECTree

     2 Transferases

         2.3 Acyltransferases

             2.3.1 Transferring groups other than aminoacyl groups

                2.3.1.37 5-aminolevulinate synthase

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Results	in table
34	Activating Compound
9466	AA Sequence
14	Application
1	CAS Registry Number
44	Cloned(Commentary)
117	Cofactor
2	Crystallization (Commentary)
765	Disease/ Diagnostics
17	Expression
23	General Information
14	General Stability
244	Inhibitors
83	kcat/KM [mM/s]
10	Ki Value [mM]
226	KM Value [mM]
53	Localization
17	Metals/Ions
74	Molecular Weight [Da]
80	Natural Substrates/ Products (Substrates)
337	Organism
1	Oxidation Stability
8	Pathway
76	PDB ID
31	pH Optimum
4	pH Range
3	pH Stability
4	Posttranslational Modification
100	Protein Variants
47	Purification (Commentary)
49	Reaction
13	Reaction Type
156	Reference
1	Renatured (Commentary)
109	Source Tissue
45	Specific Activity [micromol/min/mg]
17	Storage Stability
220	Substrates and Products (Substrate)
45	Subunits
104	Synonyms
1	Systematic Name
19	Temperature Optimum [°C]
15	Temperature Stability [°C]
90	Turnover Number [1/s]

General Information

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General Information on EC 2.3.1.37 - 5-aminolevulinate synthase

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GENERAL INFORMATION

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

evolution

Homo sapiens

P22557

vertebrate genomes encode two highly conserved, but differentially expressed, ALAS genes, a housekeeping gene (ALAS1)5,6 and an erythroid-specific gene (ALAS2)

735684

malfunction

6 entries

metabolism

8 entries

physiological function

5 entries

additional information

6 entries

malfunction

Drosophila melanogaster

-

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

malfunction

Homo sapiens

P22557

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

malfunction

Mus musculus

P08680

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

malfunction

Homo sapiens

P22557

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

malfunction

Homo sapiens

P22557

enzyme mutations are associated with two different blood disorders, X-linked sideroblastic anemia and X-linked protoporphyria

756091

malfunction

Mus musculus

P08680

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

metabolism

Mus musculus

P08680

5-aminolevulinate synthase catalyzes the first committed step of heme biosynthesis in animals

737145

metabolism

Mus musculus

P08680

5-aminolevulinate synthase catalyzes the initial step of mammalian heme biosynthesis

736491

metabolism

Mus musculus

P08680

5-aminolevulinate synthase catalyzs the initial step of mammalian heme biosynthesis

736116, 736454

metabolism

Mus musculus

-

5-aminolevulinate synthase catalyzs the initial step of mammalian heme biosynthesis

736454

metabolism

Homo sapiens

P22557

the enzyme catalyzes the first and rate-limiting step of heme formation

735684

metabolism

Mus musculus

P08680

the enzyme catalyzes the first step of heme formation

735711

metabolism

Rattus norvegicus

-

rate-limiting enzyme of heme biosynthesis

757560

metabolism

Saccharomyces cerevisiae

P09950

the enzyme catalyzes the first step in heme biosynthesis

758491

physiological function

Mus musculus

-

construction of a green fluorescent protein knock-in mouse line in which the Alas1 gene encoding ALAS-N is replaced with a green fluorescent protein gene. Mice bearing a homozygous knock-in allele Alas1GFP /GFP are lethal by embryonic day 8.5. The Alas1 expression level differs substantially in tissues

703855

physiological function

Homo sapiens

P22557

silencing by shRNA results in a decrease in iron-induced expression of band 3 protein

703095

physiological function

Xenopus laevis

Q68F30

aminolevulinate synthase 2 mediates erythrocyte differentiation by regulating larval globin expression during Xenopus primary hematopoiesis

735604

physiological function

Homo sapiens

P22557

the extended C-terminus of wild-type mammalian ALAS2 provides a regulatory role that allows for allosteric modulation of activity, thereby controlling the rate of erythroid heme biosynthesis, regulation of 5-aminolevulinate synthase is at the origin of balanced heme production in mammals

735684

physiological function

Rhodobacter capsulatus

-

coexpression of the enzyme improves the heterologous production of cytochrome P450, CYP119, from Sulfolobus acidocaldarius in Escherichia coli

756455

additional information

Mus musculus

P08680

residue Asn150 is essential for establishing a catalytic balance between the forward and reverse reactions

736491

additional information

Mus musculus

-

residue Asn150 is essential for establishing a catalytic balance between the forward and reverse reactions

736491

additional information

Mus musculus

P08680

the adenosyl-binding site Lys221 contributes to binding and orientation of succinyl-CoA for effective catalysis

736116

additional information

Mus musculus

-

the adenosyl-binding site Lys221 contributes to binding and orientation of succinyl-CoA for effective catalysis

736116

additional information

Homo sapiens

P22557

the N-terminal region, designated as region 2 and encoded by exons 3 and 4 of the human ALAS2 gene, is not required for activity and contains an heme-regulatory motif

735684

additional information

Homo sapiens

-

the N-terminal region, designated as region 2 and encoded by exons 3 and 4 of the human ALAS2 gene, is not required for activity and contains an heme-regulatory motif

735684