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Literature summary extracted from

  • Clavero, S.; Bishop, D.F.; Haskins, M.E.; Giger, U.; Kauppinen, R.; Desnick, R.J.
    Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations (2010), Hum. Mol. Genet., 19, 584-596.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.5.1.61 medicine cats with naturally occurring mutant enzymes can be used as animal model for acute intermittent porphyria Felis catus

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.61 expression in Escherichia coli BL21+ Felis catus

Protein Variants

EC Number Protein Variants Comment Organism
2.5.1.61 A84T type OregonAR (c250G>A), autosomal recessive, therefore phenotype is homozygous, about 35% wild type activity Felis catus
2.5.1.61 L64S c.189dupT mutant type Saskatchewan with duplication that leads to a frameshift and thus to a trunkated enzyme due to a premature stop codon 65 and the exchange L64S, autosomal dominant Felis catus
2.5.1.61 additional information 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way Felis catus
2.5.1.61 additional information 4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way Felis catus
2.5.1.61 additional information type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity Felis catus
2.5.1.61 R149W type Missouris (c.445C>T), substitution identical to human mutation but there leading to an nonsense mutation, autosomal dominant, less than 1% wild type activity Felis catus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.5.1.61 40500
-
 erythroid enzyme, SDS-PAGE Felis catus
2.5.1.61 43000
-
 housekeeping enzyme, SDS-PAGE Felis catus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.61 4 porphobilinogen + H2O Felis catus
-
 hydroxymethylbilane + 4 NH3
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.61 Felis catus D3W810 wild type siblings of mutant cats or unrelated wild type cats, porphyric mutant cats type Saskatchewan (c.189dupT = trunkated (premature stop codon 65) L64S), type Massachusetts (c842_844delGAG = delGly281), type Missouris (c.445C>T = R149W), type OregonAR (c250G>A = A84T)
-
2.5.1.61 Felis catus D3W811 wild type siblings of mutant cats or unrelated wild type cats, porphyric mutant cats type Saskatchewan (c.189dupT = trunkated (premature stop codon 65) L64S), type Massachusetts (c842_844delGAG = delGly281), type Missouris (c.445C>T = R149W), type OregonAR (c250G>A = A84T)
-
2.5.1.61 Felis catus D3W812 wild type siblings of mutant cats or unrelated wild type cats, porphyric mutant cats type Saskatchewan (c.189dupT = trunkated (premature stop codon 65) L64S), type Massachusetts (c842_844delGAG = delGly281), type Missouris (c.445C>T = R149W), type OregonAR (c250G>A = A84T)
-
4.2.1.75 Felis catus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.5.1.61 packed red blood cells are washed in phosphate buffered saline, lysed with buffer containing 0.1 M KHEPES, pH 7.5, 0.1% Triton X-100, 1 mM DTT, and 0.02% sodium azide, liver and spleen are diced and homogenized in buffer containing 50 mM KHEPES, pH 7.5, 150 mM KCl, 1 mM Na2EDTA, 1 mM DTT, 0.1 mM PMSF, for activity and thermostability experiments enzymes are expressed in Escherichia coli, cells are harvested and resuspended in 50 mM HEPES, pH 7.8, 0.5 M NaCl, 5 mM DTT, 330 microg/ml lysozyme, 5 microg/ml DNAse and RNAse, freeze-thawed 3times in dry-ice/ethanol, centrifuged, adjusted to pH 7.4 and 8.0 with NaOH, incubated at 37°C or 50°C for 1 h Felis catus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.5.1.61 erythrocyte
-
 Felis catus
-
2.5.1.61 liver
-
 Felis catus
-
2.5.1.61 spleen
-
 Felis catus
-
4.2.1.75 erythrocyte
-
 Felis catus
-
4.2.1.75 liver
-
 Felis catus
-
4.2.1.75 spleen
-
 Felis catus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.61 4 porphobilinogen + H2O
-
 Felis catus hydroxymethylbilane + 4 NH3
-
 ?
4.2.1.75 hydroxymethylbilane
-
 Felis catus uroporphyrinogen III + H2O
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.61 HMBS1a-synthase housekeeping, GenBank GQ850461, isolated from liver Felis catus
2.5.1.61 HMBS1b-synthase housekeeping, truncated form, GenBank GQ850462, isolated from liver Felis catus
2.5.1.61 HMBS2a-synthase erythroid-specific, GenBank GQ850463, isolated from spleen Felis catus
2.5.1.61 HMBS2b-synthase erythroid-specific, GenBank GQ850464, isolated from spleen Felis catus
2.5.1.61 hydroxymethylbilane synthase
-
 Felis catus
4.2.1.75 URO-synthase
-
 Felis catus
4.2.1.75 uroporphyrinogen-III-synthase
-
 Felis catus

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.5.1.61 50
-
 A84T mutant houskeeping enzyme (OregonAR cat) at pH 8.0 has a prolonged half-life of 6.9 h compared to 1.9 h for the wild-type Felis catus

Expression

EC Number Organism Comment Expression
4.2.1.75 Felis catus the hepatic and splenic URO-synthase activities are normal or elevated (1-1.6fold) compared with age and sex-matched feline control activities in the dominantly inherited acute intermittent porphyria lines up

General Information

EC Number General Information Comment Organism
2.5.1.61 malfunction half-maximal activity of the enzyme causes acute intermittent porphyria due to an error of heme biosynthesis Felis catus