Ketoglutarate -dependent enzymes

Figure 13.21 Mononuclear non-haem iron enzymes from each of the five families in structures which are poised for attack by 02. (a) The extradiol-cleaving catechol dioxygenase, 2,3-dihydroxy-biphenyl 1,2-dioxygenase (b) the Rieske dioxygenase, naphthalene 1,2-dioxygenase (c) isopenicillin N-synthase (d) the ot-ketoglutarate dependent enzyme clavaminate synthase and (e) the pterin-dependent phenylalanine hydroxylase. (From Koehntop et al., 2005. With kind permission of Springer Science and Business Media.)...

Scheme 9.38 Trichlorination of leucine with enzymes from the barbamide biosynthesis pathway (BarBl. BarB2 represent nonheme iron ketoglutarate-dependent halogenases).

The a-ketoacid-dependent enzymes are distinguished from other non-haem iron enzymes by their absolute requirement for an a-ketoacid cofactor as well as Fe(II) and O2 for activity. They catalyse two types of reaction (Table 2.3), hydroxyla-tion and oxidation. In both, the a-ketoglutarate is decarboxylated and one oxygen atom introduced into the succinate formed in the hydroxylases, the other oxygen atom is introduced into the substrate, while in the oxidases it is found in water, together with the cyclized product. In general these enzymes require one equivalent of Fe(II) an a-ketoacid, usually a-ketoglutarate and ascorbate. Examples of these enzymes include proline 4-hydroxylase, prolyl and lysyl hydroxylase, which... 

This enzyme [EC 2.6.1.42], also referred to as transaminase B, catalyzes the reversible reaction of leucine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-methyl-2-oxopentanoate and glutamate. The pyridoxal-phosphate-dependent enzyme will also utilize isoleucine and valine as substrates. However, this enzyme is distinct from that of valine pyruvate aminotransferase [EC 2.6.1.66]. See also Leucine Aminotransferase... 

This pyridoxal 5-phosphate-dependent enzyme [EC 2.6.1.4] catalyzes the transamination of glyoxylate from L-glutamate to produce glycine and a-ketoglutarate. 

This pyridoxal-phosphate-dependent enzyme [EC 2.6.1.6] catalyzes the reversible reaction of leucine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-methyl-2-oxopentanoate and glutamate. See also... 

Two distinct IDHs have been identified in living organisms NAD-IDH (EC 1.1.1.41) is limited exclusively to eukaryotic organisms, and NADP-IDH (EC 1.1.1.42) is ubiquitously present in both prokaryotes and eukaryotes [15], These enzymes play important biological roles NAD-IDH is involved in the supply of NADH used for respiratory ATP production in mitochondria of eukaryotic organisms the bacterial NADP-IDH is also part of the Krebs cycle machinery. However, the eukaryotic NADP-dependent enzyme is primarily involved in providing NADPH and a-ketoglutarate for biosynthesis [15],... 

Zhou J, Gunsior M, Bachmann BO, Townsend CA, Solomon El. Substrate binding to the a-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2 coupling mechanism of oxidative decarboxylation and hydroxylation. J. Am. Chem. Soc. 1998 120 13539-13540. 

An unusual sulfatase mechanism is observed for alkyl sulfatases from the nonheme Fe, a-ketoglutarate-dependent dioxygenase superfamilyThese enzymes cleave a variety of sulfate esters by a complex radical mechanism, yielding the corresponding aldehyde and inorganic sulfate. The crystal structure of AtsK from Pseudomonas putida, a member of this group of enzymes, has been solved and a mechanism proposed... 

The other major class of nonheme iron-dependent dioxygenases are the a-ketoglutarate-dependent dioxygenases, which catalyze the oxidative decarboxylation of cosubstrate a-ketoglutarate to form succinate and an iron(IV)-oxo intermediate, which is then used to carry out a range of hydroxylation, desaturation, and other oxidative reactions. While the majority of reactions catalyzed by this family of enzymes are involved in biosynthetic pathways, enzymes such as HPPD (see Section 8.16.2.1) are involved in degradation pathways, therefore it is appropriate to discuss this family of enzymes, and contrast them with the nonheme iron-dependent dioxygenases described in Section 8.16.1. 

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