5,6-dihydroxyindole-2-carboxylic acid oxidase

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5,6-dihydroxyindole-2-carboxylic acid oxidase
Properties of human protein
Mass / length primary structure 513 amino acids
Secondary to quaternary structure single pass type 1 membrane protein
Cofactor 2 copper
Identifier
Gene name TYRP1
External IDs
Enzyme classification
EC, category 1.14.18.- ,  oxidoreductase
Substrate 5,6-dihydroxyindole-2-carboxylate (DHICA)
Products (Poly) melanin
Occurrence
Homology family Tyrosinase
Parent taxon Creature

5,6-Dihydroxyindole-2-carboxylic acid oxidase , DHICA oxidase for short ( gene : TYRP1 , from earlier tyrosinase-related protein 1 (Trp-1) ) is the enzyme that converts 5,6-dihydroxyindole-2-carboxylic acid into melanin . It is therefore essential for one of two metabolic pathways through which the pigment melanin is built up in melanocytes . Mutations in the TYRP1 gene are responsible for oculocutaneous albinism type 3 . Animals immunized with this enzyme show symptoms of Vogt-Koyanagi-Harada syndrome .

One allele of TYRP1 in humans is typical of people of the Solomon Islands with blonde hair. Even if these look similar to the European expression, this allele does not occur in Europeans. The variation is likely 10,000 years old.

Catalyzed reaction

5,6-dihydroxyindole-2-carboxylate+ 2 Ox. Acc. ⇒
⇒ Polymelanin+ 2 red. Acc. + CO 2

The carbonic acid residue is split off oxidatively from DHICA and the product polymerizes to eumelanin , a brown-black pigment which, together with other pigments, gives skin and hair its color.

More functions

DHICA oxidase forms heterodimers with tyrosinase , stabilizes them and thus possibly contributes to the regulation of melanin synthesis through the formation of a protein complex, the transcription of which is activated by a protein called Mitf .

inhibition

The active ingredient rucinol is supposed to inhibit pigment formation in a targeted manner by inhibiting tyrosinase and TRP-1.

See also

Individual evidence

  1. ↑ UniProt P17643
  2. ↑ Yamaki K, Ohono S: Animal models of Vogt-Koyanagi-Harada disease (sympathetic ophthalmia) . In: Ophthalmic Res . 40, No. 3-4, 2008, pp. 129-35. doi : 10.1159 / 000119863 . PMID 18421226 .
  3. ↑ New Scientist, Blonde hair - so good we evolved it (at least) twice , Vol. 214, No. 2864, p. 16
  4. ↑ Alonso S, Izagirre N, Smith-Zubiaga I, et al : Complex signatures of selection for the melanogenic loci TYR, TYRP1 and DCT in humans . In: BMC Evol. Biol . 8, 2008, p. 74. doi : 10.1186 / 1471-2148-8-74 . PMID 18312627 .
  5. ↑ dirt SM, Berryere TG: Genes Affecting coat color and pattern in domestic dogs: a review . In: Anim. Genet. . 38, No. 6, December 2007, pp. 539-49. doi : 10.1111 / j.1365-2052.2007.01664.x . PMID 18052939 .
  6. ↑ Kobayashi T, Hearing VJ: Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo . In: J. Cell. Sci. . 120, No. Pt 24, December 2007, pp. 4261-8. doi : 10.1242 / jcs.017913 . PMID 18042623 .
  7. ↑ Ray K, Chaki M, Sengupta M: Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1 . In: Prog Retin Eye Res . 26, No. 4, July 2007, pp. 323-58. doi : 10.1016 / j.preteyeres.2007.01.001 . PMID 17355913 .
  8. ↑ Denat L, Larue L: [Malignant melanoma and the role of the paradoxal protein Microphthalmia transcription factor .] In: Bull Cancer . 94, No. 1, January 2007, pp. 81-92. PMID 17237008 .
  9. ↑ Kim DS, Kim SY, Park SH, et al : Inhibitory effects of 4-n-butylresorcinol on tyrosinase activity and melanin synthesis . (PDF) In: Biol Pharm Bull . 28, No. 12, December 2005, pp. 2216-9. PMID 16327152 .

Web links

Wikibooks: Tyrosine Metabolism  - Learning and Teaching Materials