Dihydroorotate Dehydrogenase: A Mitochondrial Enzyme Of Pyrimidine Biosynthesis
Sukumar Taria - Scientist, Plant Science, Krishi Vigyan Kendra, Puri, OUAT, BBSR-751003
Gopa Mishra - Ph.D Scholar,Department Of Fruit Science and Horticulture Technology, OUAT, BBSR-751003
Pyrimidine biosynthesis differs significantly from purine biosynthesis in that ring is synthesized first and then attached to the ribose moieties as 5-phosphoribosyl-1-pyrophosphate (PRPP). In bacteria, the first three enzymes of the pathways namely carbamoyl phosphate synthetase II, aspartate transcarbamoylase and dihydroorotate dehydrogenase function as multienzymes complex, contain three different polypeptide having three different active site for these reaction.
Carbamoyl phosphate synthatase I is involved in the biosynthesis of uric acid which is present in the mitochondrial matrix where as carbamoyl phosphate synthatase I is present in the cytosol. The reaction catalysed by the aspartate transcarbamoylase is the regulatory step in the pyrimidine synthesis. Out of the several enzymes involved in the pyrimidine biosynthesis which are cytosolic enzymes, the reaction catalysed by the dihydroorotate dehydrogenase is the only mitochondrial enzyme present in the outer surface of the inner membrane.
DHODH can vary in cofactor content, oligomeric state, sub cellular localization, and membrane association. There are two classes of dihydroorotate dehydrogenase (DHODHs): the cytosolic Class 1 and the membrane-bound Class 2. In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, where as in Class 2, the serine serves this catalytic function.
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other is heterotetramers and uses NAD+ as its electron acceptor. This second subclass contains an addition subunit (PyrK) containing an iron-sulfur cluster and a flavin adenine dinucleotide (FAD). Meanwhile, Class 2 DHODHs use coenzyme Q/ ubiquinones for their oxidant.
In higher eukaryotes, this class of DHODH contains an N-terminal bipartite signal comprising a cationic, amphipathic mitochondrial targeting sequence of about 30 residues and a hydrophobic transmembrane sequence.
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