Butyrobetaine hydroxylase

Proline and lysine hydroxylases are required for the postsynthetic modification of collagen, and proline hydroxylase also for the postsynthetic modification of osteocalcin in bone and the Clq component of complement. Aspartate / -hydroxylase is required for the postsynthetic modification of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood-clotting cascade. Trimethyllysine and 7-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.

Butyrobetaine hydroxylase Oxidation of 4-butyrobetaine aldehyde Carnitine synthesis... 

Carnitine biosynthesis in humans. A lysyl residue is trimethylated by S-adenosyimethionine, with subsequent proteolytic release of trimethyllysine, the starting material. The reactions are catalyzed by (1) trimethyllysine A-hydroxylase, (2) /t-hydroxy-trimethyllysine aldolase (pyridoxal phosphate), (3) )/-trimethylaminobutyraldehyde dehydrogenase, and (4) /-butyrobetaine hydroxylase. 

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. 

Butyrobetaine hydroxylase (E.C. 1.14.11.1 - 4-Trimethylamino-butyrate, 2-oxoglutarate oxygen oxidoreductase (3-(/ )-hydroxylat-ing) (2). 

All the enzymes contain ferrous iron. Ferrous ions are essential for the catalytic activity of butyrobetaine hydroxylase (259), proline-4- 254) and 3- 242, 243), hydroxylases, thymidine hydroxylase 260), lysine hydroxylase 261), trimethyllysine hydroxylase 247), thymine oxygenase 262—264), cephalosporin hydroxylase 249), and hydroxy-phenylpyruvate 265—267). In addition, the enzymes show a non-stoichio-metric requirement for ascorbic acid which is supposed to maintain the ion co-factor in the ferrous oxidation state (2, 242, 243, 254). Labelling studies with butyrobetaine hydroxylase 268), proline-4-hydroxylase 269), thymine oxygenase (270), cephalosporin hydroxylase (257) and hydroxy-phenylpyruvate hydroxylase (277) all indicate a common pattern of oxygen incorporation. One atom of oxygen becomes the new hydroxyl group while the other is located in one of the carboxylic acid groups of succinic acid. 

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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