PMID- 11171088
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 354
IP  - Pt 1
DP  - 2001 Feb 15
TI  - The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human 
      tyrosinase.
PG  - 131-9
AB  - Melanin synthesis in mammals is catalysed by at least three enzymic proteins, 
      tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 
      1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to 
      the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the 
      rate-limiting generation of L-dopaquinone from L-tyrosine and is also able to 
      oxidize L-dopa to L-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, 
      catalyses the oxidation of the indolic intermediate 
      5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 
      5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA 
      units into eumelanin. The catalytic activities of the human melanogenic enzymes 
      are still debated. TYRP1 has been reported to lack DHICA oxidase activity, 
      whereas tyrosinase appears to accelerate DHICA consumption, thus raising the 
      question of DHICA metabolism in human melanocytes. Here we have used two 
      different approaches, comparison of the catalytic activities of human melanocytic 
      cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, 
      and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that 
      human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse 
      enzyme. Therefore, human tyrosinase displays a broader substrate specificity than 
      its mouse counterpart, and might be at least partially responsible for the 
      incorporation of DHICA units into human eumelanins.
FAU - Olivares, C
AU  - Olivares C
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, University 
      of Murcia, Apto 4021, Campus Espinardo, 30100 Murcia, Spain.
FAU - Jimenez-Cervantes, C
AU  - Jimenez-Cervantes C
FAU - Lozano, J A
AU  - Lozano JA
FAU - Solano, F
AU  - Solano F
FAU - Garcia-Borron, J C
AU  - Garcia-Borron JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Cell Extracts)
RN  - 0 (DNA Primers)
RN  - 0 (Melanins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.18.- (TYRP1 protein, human)
RN  - EC 1.14.18.- (tyrosinase-related protein-1)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Cell Extracts
MH  - DNA Primers
MH  - Humans
MH  - Melanins/biosynthesis
MH  - Melanoma/enzymology/metabolism/pathology
MH  - *Membrane Glycoproteins
MH  - Molecular Sequence Data
MH  - Monophenol Monooxygenase/chemistry/*metabolism
MH  - Oxidation-Reduction
MH  - *Oxidoreductases
MH  - Proteins/chemistry/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Tumor Cells, Cultured
PMC - PMC1221637
EDAT- 2001/02/15 11:00
MHDA- 2001/04/03 10:01
PMCR- 2001/08/15
CRDT- 2001/02/15 11:00
PHST- 2001/02/15 11:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2001/02/15 11:00 [entrez]
PHST- 2001/08/15 00:00 [pmc-release]
AID - 10.1042/0264-6021:3540131 [doi]
PST - ppublish
SO  - Biochem J. 2001 Feb 15;354(Pt 1):131-9. doi: 10.1042/0264-6021:3540131.