Galactosylation of collagen propeptide hydroxylysines by procollagen galactosyltransferases 1, 2

Hydroxylysine glycosides are specific to collagen. Collagen glycosylation takes place in the endoplasmic reticulum before triple-helix formation. Either galactose or glucose-galactose are attached to approximately one third of hydroxylysine residues by specific transferases, beta(1-O)galactosyl- and alpha(1-2)glucosyltransferase, forming galactosyl hydroxylysine (Gal-Hyl) and glucosyl-galactosyl hydroxylysine (Glu-Gal-Hyl) respectively. The genes GLT25D1 and GLT25D2 encode galactosyltransferases that are active with various types of collagen and the serum mannose-binding lectin MBL, which also contains a collagen domain. GLT25D1 gene is constitutively expressed in human tissues, whereas the GLT25D2 gene was found to be expressed only at low levels in the nervous system. These galactosyltransferases convert 5-hydroxylysine to 5-galactosyl hydroxylysine (Gal-Hyl). The extent of hydroxylysine galactosylation is variable between collagen types and locations; it is particularly common in bone type I collagen (Al-Dehaimi et al. 1999). Although the fraction of hydroxylysine residues that are glycosylated does not differ between skin and bone (the major sources of type I collagen) the pattern of hydroxylysine glycosylation is different. Glu-Gal-Hyl predominates in skin, where the Glu-Gal-Hyl/Gal-Hyl ratio is approximately 2 (Pinnell et al. 1971), whereas Gal-Hyl predominates in bone, where the Glu-Gal-Hyl/Gal-Hyl ratio is 0.47 (Krane et al. 1977).

羟基赖氨酸糖苷是胶原蛋白的特异性标志。胶原蛋白的糖基化过程发生在内质网中，此过程先于三螺旋结构的形成。通过特定的转移酶，如β(1-O)半乳糖基转移酶和α(1-2)葡萄糖基转移酶，将半乳糖或葡萄糖-半乳糖分别连接到约三分之一的羟基赖氨酸残基上，从而形成半乳糖基羟基赖氨酸（Gal-Hyl）和葡萄糖基-半乳糖基羟基赖氨酸（Glu-Gal-Hyl）。基因GLT25D1和GLT25D2编码的半乳糖基转移酶能够与多种类型的胶原蛋白以及血清中的甘露糖结合凝集素MBL（含有胶原蛋白结构域）发生作用。GLT25D1基因在人类组织中恒定表达，而GLT25D2基因仅在神经系统中发现低水平表达。这些半乳糖基转移酶将5-羟基赖氨酸转化为5-半乳糖基羟基赖氨酸（Gal-Hyl）。胶原蛋白中羟基赖氨酸的半乳糖化程度在不同类型和不同部位之间存在差异；尤其是在I型骨胶原蛋白中（Al-Dehaimi等，1999年），该现象尤为常见。尽管在皮肤和骨骼（I型胶原蛋白的主要来源）中糖基化的羟基赖氨酸残基比例无显著差异，但羟基赖氨酸糖基化的模式却不同。在皮肤中，Glu-Gal-Hyl/Gal-Hyl的比例约为2（Pinnell等，1971年），而在骨骼中，该比例降至0.47（Krane等，1977年）。