Biological Chemistry - Berezov, T. T., & Korovkin, B. F. 1998

Connective Tissue
Extracellular Organic Matrix of Connective Tissue
Collagen

A characteristic structural component of Connective Tissue is Collagen fibers. They are constructed primarily from a unique protein known as collagen. Collagen accounts for 25–33% of the total protein content in an adult human body, or 6% of body weight.

Collagen fibers visible under a Light Microscope consist of fibrils discernible only with an Electron microscope, which are elongated protein molecules called tropocollagen. Tropocollagen is the primary structural unit of collagen (Fig. 21.2). It is essential to clearly distinguish between The concepts of "collagen fibers" and "collagen." The former concept is essentially morphological and cannot be reduced to biochemical ideas of collagen simply as a protein. A collagen fiber is a heterogeneous Structure containing other chemical components In addition to the protein collagen. The tropocollagen molecule is, in fact, the protein collagen. One of the distinguishing features of this protein is that ¹/₃ of all its amino acid residues are Glycine, ¹/₃ are Proline and 4-hydroxyproline, about 1% is hydroxylysine, and some molecular forms of collagen also contain 3-hydroxyproline, albeit in very limited amounts:

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The Molecular Weight of tropocollagen is approximately 285,000. Tropocollagen consists of three polypeptide chains of equal size that wind together into a helical triplet. The triple helix is stabilized by numerous interfibrillar and interchain cross-links between Lysine and hydroxylysine residues. Each polypeptide chain of tropocollagen contains about 1,000 amino acid residues. Thus, the fundamental structural unit of collagen is exceptionally large—for instance, roughly 10 times larger than Chymotrypsin.

Studies of the Amino Acid Composition and sequence in The polypeptide chains of tropocollagen have demonstrated the existence of two main chain types, a1 and a2, as well as four Variants of the a1 chain: a1 (I), a1 (II), a1 (III), and a1 (IV). Data on The structure of collagens from various Tissues are presented in Table 21.1.

Table 21.1. Types of collagens and some of their structural properties (according to White et al., 1981)

Like all Proteins, collagen is synthesized by Cells from free amino acid residues. Hydroxyproline and hydroxylysine, The amino acid residues specific to the collagen molecule, are not formed directly from their corresponding free Amino Acids. Instead, these residues are generated after proline and lysine have been incorporated into the polypeptide chain through the action of the Enzymes prolyl hydroxylase or lysyl hydroxylase, requiring ascorbic acid as a cofactor.

Given the presence of different molecular forms within a single type (for example, type I collagen has either the composition [a1 (I)]₂a2 or [a1 (I)]₃), there is good reason to believe that at least 10 distinct molecular forms of collagen exist (E.S. Severin).

Recall that collagen is an extracellular protein, yet it is initially synthesized as an intracellular precursor molecule that undergoes post-translational modification before mature collagen fibrils are formed. The collagen precursor (first preprocollagen, then procollagen) undergoes Processing as it passes through the Endoplasmic reticulum and the Golgi apparatus before emerging into the extracellular space. Extracellular procollagen amino- and carboxy-proteinases cleave the amino-terminal and carboxy-terminal propeptides, respectively. The newly formed collagen molecules then spontaneously assemble into collagen fibrils. Through cross-linking of the chains and helical molecules within the fibrils via Schiff base formation and aldol Condensation (i.e., stabilization via a series of covalent bonds), the resulting fibrils acquire the tensile strength characteristic of mature collagen fibers.