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Lysine 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. [Pg.496]

Hydroxylation of lysine Iron lysine hydroxylase (animals)... [Pg.353]

Ehlers-Danlos syndromes Mutations in collagen genes and lysine hydroxylase gene Hyperextensible, fragile skin HypermobUe joints, dislocations, varicose veins, ecchymoses, arterial, intestinal ruptures... [Pg.60]

The formation of Hyp and Hyl residues in procollagen is catalyzed by iron-containing oxygenases ( proline and lysine hydroxylase, EC 1.14.11.1/2). Ascorbate is required to maintain their function. Most of the symptoms of the vitamin C deficiency disease scurvy (see p. 368) are explained by disturbed collagen biosynthesis. [Pg.344]

Procollagen lysine 5-dioxygenase [Fe, ascorbate]— lysine hydroxylase ... [Pg.422]

One-third of the amino acid residues in collagen are Gly, while another quarter are Pro. The hydroxylated amino acids 4-hydroxyproline (Hyp) and 5-hydroxylysine (Hyl) are formed post-translationally by the action of proline hydroxylase and lysine hydroxylase. These Fe2+-containing enzymes require ascorbic acid (vitamin C) for activity. In the vitamin C deficiency disease scurvy, collagen does not form correctly due to the inability to hydroxylate Pro and Lys. Hyl residues are often post-translationally modified with carbohydrate. [Pg.43]

Proline/lysine hydroxylase (mammalian) mononuclear iron complement Clq and collagen synthesis Substrate carbanion and iron bound hydroxyl 3.2.2. [Pg.69]

Progressive fibro-proliferative diseases (e.g. liver cirrhosis, pulmonary fibrosis, rheumatoid arthritis) result in a dramatic increase in collagen synthesis [227], This is preceded by inflammation that correlates with an increased activity of proline and lysine hydroxylase [228], Although they are unlikely to be the primary initiators of these diseases the increased activities of these enzymes may cause other problems. For example, in vitro the enzyme can turn over in the absence of a peptide substrate (but the presence of the 2-oxoglutarate cofactor). In this case stoichiometric amounts of ascorbate are required, probably to reduce the ferryl ion back to ferrous [229]. In vivo, lower concentrations of ascorbate are utilised [229,230], possibly to reactivate the enzyme after a non-productive activation (for example in the presence of a peptide that can bind to the active site, but cannot be hydroxylated). As the amount of proline-hydroxylase activity increases in the fibro-proliferative diseases, the concentration of ascorbate might not be sufficient to reduce these inactive complexes, resulting in the formation of potentially reactive ferryl intermediates. [Pg.101]

The ability to synthesise ascorbic acid from glucose is absent in a small group of animal species that include man, primates, the guinea pig and the fruit-bat this is due to the absence of the gene that codes for one of the enzymes required for ascorbate synthesis. These species are therefore dependent on an external source of the vitamin in their diet and it is needed as a cofactor for several hydroxylase enzymes, notably the iron-dependent proline and lysine hydroxylases and the copper-dependent dopamine-(3-hydroxylase the function of ascorbate in these enzymes is likely to be its ability to keep the metal in the reduced form which is necessary for hydroxylation. The ability of ascorbate to reduce Fe3+ to Fe2+ is important in promoting the gastrointestinal uptake of iron and for its release from the iron store ferritin. [Pg.122]

Ascorbic acid has specific and weU-deflned roles in two classes of enzymes the copper-containing hydroxylases (such as dopamine /3-hydroxylase and peptidyl glycine hydroxylase) and the 2-oxoglutarate-linked iron-containing hydroxylases, of which the best studied are the proline and lysine hydroxylases involved in maturation of connective tissue (and other) proteins. [Pg.364]

Procollagen proline 4-hydroxylase is the best studied of this class of enzymes it is assumed that the others have essentially the same mechanism, although proline and lysine hydroxylases show very little sequence homology (Kivirikko and Pihlajaniemi, 1998). Although 3-hydroxyproline is found only in collagen, 4-hydroxyproline and hydroxylysine are found in a variety of other proteins, including the Clq component of complement, osteocalcin, macrophage receptor proteins, and a variety of transmembrane and intercellular proteins and proteins of the cytoskeleton, as weU as some enzymes. 4-Hydroxyproline, but not hydroxylysine, also occurs in elastin. [Pg.367]

Proline and lysine hydroxylases are found in the lumen of rough endoplasmic reticulum. Hydroxylation of the peptide substrate occurs both cotransla-tionaUy and later as a postsynthetic modification. The enzymes act only on peptides and not on free amino acids. [Pg.368]

Most of the other clinical signs of scurvy can be accounted for by effects of deficiency on collagen synthesis as a result of impaired proUne and lysine hydroxylase activity (Section 13.3.3). [Pg.372]

The enzyme that catalyzes this reaction, lysine hydroxylase, is, like prolyl hydroxylase, a Fe(II)/2-oxoglutarate dependent dioxygenase but exhibits a distinct substrate specificity. [Pg.5497]

Lysine hydroxylase Posttranslational hydroxylation of lysine Crosslinking of collagen... [Pg.417]

Trimethyl lysine hydroxylase Hydroxylation of trimethyl lysine Carnitine synthesis... [Pg.417]

EDS-V is an X-linked form of EDS-I in which skin fragility is prominent. EDS VI is a severe form of EDS-I associated with corneal degeneration. The genetic mutations of both are unknown, but EDS-VI has reduced lysine hydroxylase activity despite no detectable mutation of any of its three genes (Sect. 7.3.1) or of the genes involved in ascorbate metabolism (Sect. 7.4.1). [Pg.106]

Fig. 7.5 Structure of the diglycan attached to hydroxylysine. The LH3 isoform of lysine hydroxylase attaches UDP- galactose to hydroxylysine in a fi-linkage, and then a-links UDP glucose to the C2 atom of the galactose. This reaction occurs in the endoplasmic reticulum and in the connective tissue matrix (From Fig. 11.4 in Biochemistry, L. Stryer, 3rd Ed. 1988. W.H. Freeman Co., New York)... Fig. 7.5 Structure of the diglycan attached to hydroxylysine. The LH3 isoform of lysine hydroxylase attaches UDP- galactose to hydroxylysine in a fi-linkage, and then a-links UDP glucose to the C2 atom of the galactose. This reaction occurs in the endoplasmic reticulum and in the connective tissue matrix (From Fig. 11.4 in Biochemistry, L. Stryer, 3rd Ed. 1988. W.H. Freeman Co., New York)...
Vitamin C (ascorbic acid, Fig. 2) is a water-soluble vitamin that dissociates at physiological pH. It is essential as a cofactor of several enzymes, including proline hydroxylase and lysine hydroxylase. Scurvy is known as the result of malnutrition with ascorbic acid. This vitamin deficiency is characterized by instable collagen. This results from insufficient hydroxylation of collagen molecules. Besides this, ascorbic acid has a function as an antioxidant. [Pg.81]


See other pages where Lysine hydroxylase is mentioned: [Pg.229]    [Pg.44]    [Pg.45]    [Pg.203]    [Pg.367]    [Pg.367]    [Pg.367]    [Pg.5496]    [Pg.5497]    [Pg.367]    [Pg.351]    [Pg.101]    [Pg.107]    [Pg.108]    [Pg.108]    [Pg.109]    [Pg.109]    [Pg.109]    [Pg.118]   
See also in sourсe #XX -- [ Pg.44 , Pg.45 ]

See also in sourсe #XX -- [ Pg.367 ]

See also in sourсe #XX -- [ Pg.107 ]

See also in sourсe #XX -- [ Pg.84 ]

See also in sourсe #XX -- [ Pg.242 , Pg.243 ]




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