Y-butyrobetaine hydroxylase

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

The mechanism of a-ketoglutarate participation in the dioxygenase reaction has been proposed by Lindstedt and his co-workers6S,220) as shown in Eq. (27) with y-butyrobetaine hydroxylase. 

In general, the effects on collagen synthesis are more marked and more important than those of decreased formation of carnitine (as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases Section 14.1.1), impaired xenobiotic metabolism, or hypercholesterolemia (Section 13.3.8). However, depletion of muscle carititine may account for the lassitude and fatigue that precede clinical signs of scurvy. 

In general, the effects on collagen synthesis are more marked and more important than those of decreased formation of carnitine (as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases Section... 

Figure 14.2. Biosynthesis of carnitine. Trimethyllysine hydroxylase, EC 1.14.11.8 aldolase, EC 4.1.2. x aldehyde dehydrogenase, EC 1.2.1.47 y-butyrobetaine hydroxylase, EC 1.14.11.1. Relative molecular mass (Mr) carnitine, 161.2.

In this manner, y-butyrobetaine hydroxylase catalyzes the terminal step in carnitine biosynthesis, the hydroxylation of 4-A(-trimethyl-aminobutyrate. a-Kctoglutaratc-dcpendent dioxygenases act as oxygenation catalysts only in the presence of iron ions. Formation of thermodynamically stable CO2 helps to produce a high-valent center (Scheme XI. 12) [38a]. 

Lindstedt, G. Linstedt, S. (1970) J. Biol. Chem., 245, 4 1 78-4 1 86, Cofactor requirements of y-butyrobetaine hydroxylase from rat liver. 

Kondo, A., Blanchard, IS. Englard, S. ( 9S )Arch. Biochem. Biophys, 212, 338-346, Purification and properties of calf liver y-butyrobetaine hydroxylase. 

Lindstedt, G, Lindstedt, S. Nordin, I. (1977) Biochemistry, 16, 2181-2188, Purification and properties of y-butyrobetaine hydroxylase from Pseudomonas sp AK 1. 

Paul, H.S., Sekas, G. Adibi, S.A. (1992) Eur. J. Biochem. 203, 599-605. Carnitine biosynthesis in hepatic peroxisomes. Demonstration of y-butyrobetaine hydroxylase activity. 

Lindstedt, G., S. Lindstedt, and I. Nordin Puriflcation and Some Properties of y-Butyrobetaine Hydroxylase from Pseudomonas sp. AK I. Biochem. 16, 2181 (1977). 

Dunn, W. A., Rettura, G., Seifter, E., and Englard, S., 1984, Carnitine biosynthesis from y butyrobe-taine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver Effect of ascorbic acid deficiency on the in situ activity of y butyrobetaine hydroxylase, J. Biol. Chem. 259 10764-10770. 

Trimethyllysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine (section 5.5.1). 

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