Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology

Enrico Garattini, Ralf Mendel, Maria João Romão, Richard Wright, Mineko Terao

Research output: Contribution to journalReview article

182 Citations (Scopus)

Abstract

The molybdo-flavoenzymes are structurally related proteins that require a molybdopterin cofactor and FAD for their catalytic activity. In mammals, four enzymes are known: xanthine oxidoreductase, aldehyde oxidase and two recently described mouse proteins known as aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2. The present review article summarizes current knowledge on the structure, enzymology, genetics, regulation and pathophysiology of mammalian molybdo-flavoenzymes. Molybdo-flavoenzymes are structurally complex oxidoreductases with an equally complex mechanism of catalysis. Our knowledge has greatly increased due to the recent crystallization of two xanthine oxidoreductases and the determination of the amino acid sequences of many members of the family. The evolution of molybdo-flavoenzymes can now be traced, given the availability of the structures of the corresponding genes in many organisms. The genes coding for molybdo-flavoenzymes are expressed in a cell-specific fashion and are controlled by endogenous and exogenous stimuli. The recent cloning of the genes involved in the biosynthesis of the molybdenum cofactor has increased our knowledge on the assembly of the apo-forms of molybdo-flavoproteins into the corresponding holo-forms. Xanthine oxidoreductase is the key enzyme in the catabolism of purines, although recent data suggest that the physiological function of this enzyme is more complex than previously assumed. The enzyme has been implicated in such diverse pathological situations as organ ischaemia, inflammation and infection. At present, very little is known about the pathophysiological relevance of aldehyde oxidase, aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2, which do not as yet have an accepted endogenous substrate.

Original languageEnglish
Pages (from-to)15-32
Number of pages18
JournalBiochemical Journal
Volume372
Issue number1
DOIs
Publication statusPublished - 15 May 2003

Fingerprint

Aldehyde Oxidase
Genetic Structures
Xanthine Dehydrogenase
Genes
Enzymes
Proteins
Flavoproteins
Purines
Flavin-Adenine Dinucleotide
Mammals
Cloning
Biosynthesis
Protein Sequence Analysis
Crystallization
Catalysis
Organism Cloning
Catalyst activity
Oxidoreductases
Ischemia
Availability

Keywords

  • Aldehyde oxidase
  • Molybdenum
  • Molybdenum cofactor
  • Molybdo-flavoenzymes
  • Xanthine dehydrogenase
  • Xanthine oxidase

Cite this

Garattini, Enrico ; Mendel, Ralf ; Romão, Maria João ; Wright, Richard ; Terao, Mineko. / Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology. In: Biochemical Journal. 2003 ; Vol. 372, No. 1. pp. 15-32.
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Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology. / Garattini, Enrico; Mendel, Ralf; Romão, Maria João; Wright, Richard; Terao, Mineko.

In: Biochemical Journal, Vol. 372, No. 1, 15.05.2003, p. 15-32.

Research output: Contribution to journalReview article

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