Collagen (CAS: 9064-67-9)

Collagen is the main structural protein of the various connective tissues in animals.

(The name collagen comes from the Greek kolla meaning glue and suffix -gendenoting

producing.) As the main component of connective tissue, it is the most abundant protein

in mammals, making up from 25% to 35% of the whole-body protein content. Collagen,

in the form of elongated fibrils, is mostly found in fibrous tissues such as tendons, ligaments

and skin, and is also abundant in corneas, cartilage, bones, blood vessels, the gut, and

intervertebral discs. The fibroblast is the most common cell that creates collagen.

In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes

one to two percent of muscle tissue, and accounts for 6% of the weight of strong, tendinous

muscles. Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed.

Chemistry

Collagen is composed of a triple helix, which generally consists of two identical chains (α1) and an

additional chain that differs slightly in its chemical composition (α2). The amino acid composition

of collagen is atypical for proteins, particularly with respect to its high hydroxyproline content. The

most common motifs in the amino acid sequence of collagen are glycine-proline-X and glycine-X-

hydroxyproline, where X is any amino acid other than glycine, proline or hydroxyproline. The

average amino acid composition for fish and mammal skin is given.

Amino acids

Collagen has an unusual amino acid composition and sequence:

–Glycine is found at almost every third residue.

–Proline makes up about 17% of collagen.

–Collagen contains two uncommon derivative amino acids not directly inserted during 

translation. These amino acids are found at specific locations relative to glycine and

are modified post-translationally by different enzymes, both of which require vitamin

C as a cofactor.

–Hydroxyproline derived from proline

–Hydroxylysine derived from lysine – depending on the type of collagen, varying

numbers of hydroxylysines are glycosylated (mostly having disaccharidesattached).

Cortisol stimulates degradation of (skin) collagen into amino acids

Collagen I formation

Most collagen forms in a similar manner, but the following process is typical for type I:

–Inside the cell

–Two types of alpha helices are formed during translation on ribosomes along the rough

endoplasmic reticulum (RER): alpha-1 and alpha-2 helices. These form peptide chains

(known as preprocollagen) have registration peptides on each end and a signal peptide.

–Polypeptide chains are released into the lumen of the RER.

–Signal peptides are cleaved inside the RER and the chains are now known as

pro-alpha chains.

–Hydroxylation of lysine and proline amino acids occurs inside the lumen. This

process is dependent on ascorbic acid (vitamin C) as a cofactor.

–Glycosylation of specific hydroxylysine residues occurs.

–Triple ɣ helical structure is formed inside the endoplasmic reticulum from

each two alpha-1 chains and one alpha-2 chain.

–Procollagen is shipped to the Golgi apparatus, where it is packaged and

secreted by exocytosis.

–Outside the cell

–Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.

–Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking (aldol

reaction) by lysyl oxidase which links hydroxylysine and lysine residues. Multiple

collagen fibrils form into collagen fibers.

–Collagen may be attached to cell membranes via several types of protein, including

 fibronectin and integrin.

Synthetic pathogenesis

Vitamin C deficiency causes scurvy, a serious and painful disease in which defective

collagen prevents the formation of strong connective tissue. Gums deteriorate and bleed,

with loss of teeth; skin discolors, and wounds do not heal. Prior to the 18th century, this

condition was notorious among long-duration military, particularly naval, expeditions

during which participants were deprived of foods containing vitamin C.

An autoimmune disease such as lupus erythematosus or rheumatoid arthritis may attack

healthy collagen fibers.

Many bacteria and viruses secrete virulence factors, such as the enzyme collagenase,

which destroys collagen or interferes with its production.