My notes on collagen

As an elementary school student, my favorite subject was Health and Science. I still remember that time when I had to study the effects of deficiencies of vitamins in the body. For example, I learned that vitamin C deficiency could cause scurvy. I did not fully understand then what scurvy was and how or why a lack of vitamin C would cause scurvy. Not until I took college biochemistry did I become inquisitive about this. I found out that scurvy is a disease associated with dysfunction of the protein collagen. Let me discuss collagen because there is now a lot of interest in this protein.

Function and 3-D structure of collagen

Collagen is one of the most abundant body proteins, comprising about 25 percent of the total amount of proteins in human. It is a fibrous protein located in the extracellular matrix of connective tissues. Collagen is a structural protein that supports body parts, such as bones, skin, teeth, cornea and blood vessels, among others. It acts like glue that connects parts of the body. Without collagen, the body would fall to pieces.

There are more than 20 types of collagen; a great majority of collagen is type I. Type I collagen is present in bones, tendons, ligaments, skin, teeth and arteries. The unique features of the various types of collagen are mainly due to variations in amino acids found in segments that can fold into different three-dimensional (3-D) structures. Nevertheless, the different types of collagen serve the same function in providing tissues form, firmness and strength.

The basic structural unit of collagen is a triple helical molecule. Type I collagen molecule is about 300 nanometers long (1 nanometer is 10-9 meter) and 1.5 nanometer in diameter. It consists of three coiled polypeptide chains, such as, two alpha1(I) chains and one alpha2(I) chain. Each chain with approximately 1,000 amino acids is wound around one another in a right-handed triple helix. Collagen molecules assemble to form long thin fibrils.

The triple-helical structure of collagen is due to a large number of amino acids glycine (Gly), proline (Pro) and hydroxyproline (Hyp). These amino acids make up the typical collagen repeating motif Gly-Pro-X or Gly-X-Hyp, where X can be any other amino acid. Glycine has no side chain and instead has a hydrogen atom which is small enough to easily fit into the crowded core of a triple helix. The inflexible angle of carbon to nitrogen peptidyl-proline bond or peptidyl-hydroxyproline bond allows each polypeptide chain to fold into a helix so that the three chains can wind together to form the rigid triple helix. Hydrogen bonds connecting hydrogen atoms in one chain with corresponding oxygen atoms in an adjacent chain are crucial in binding the polypeptide chains together.

Skin aging and collagen-related diseases

As one grows old, the ability of the skin to produce collagen diminishes resulting in wrinkles. When skin is excessively exposed to sunlight, it is damaged by the sun’s ultraviolet (UV) rays. In the UV damaged skin, collagen is broken down by the enzyme collagenase and procollagen synthesis is inhibited, causing the skin tissues to deteriorate. Protecting the skin from sunlight is an excellent way to maintain a youthful skin for a longer time.

Some genetic diseases are associated with collagen deficiency. For example, osteogenesis imperfecta, also called brittle bone disease, is due to the substitution of Gly by the bigger amino acid cysteine (Cys), thereby disrupting the repeating motif Gly-X-Pro that gives collagen its characteristic triple-helical structure. This substitution results in collagen misfolding causing bone deformity and in certain cases, leading to fatality.

Modification of procollagen after its biosynthesis is essential in the production of collagen and its organization into fibrils. A defect in this process caused scurvy that ancient sailors experienced during their long voyage because of inadequate supply of foodstuffs containing ascorbic acid (vitamin C). The synthesis of collagen requires vitamin C as a cofactor of the enzymes lysyl hydroxylase and prolyl hydroxylase needed in the hydroxylation of the amino acids lysine and proline, respectively.  Hydroxylysine and hydroxyproline are important in stabilizing the 3-D structure of collagen by a cross-linking process. In tissues deficient in vitamin C, the procollagen chains are not adequately hydroxylated, and unhydroxylated procollagen chains are degraded. Consequently, normal collagen fibrils cannot be formed, causing bone deformity, skin wounds, abnormal bleeding, ulceration of gums, loss of teeth, deterioration of immune system, and other symptoms that can lead to death. Vitamin C needed to prevent scurvy can be obtained from citrus fruits and many vegetables.

Postscript: Collagen supplements

Collagen supplements are available as collagen peptides (hydrolyzed collagen in the form of “small proteins”) or collagen constituent amino acids, usually with vitamin C and other additives. Collagen supplements are claimed to slow down the aging process by replenishing the collagen, thereby aiding the body to maintain a youthful look. The supplements are also believed to relieve inflammation and pain in joints, as in the case of rheumatoid arthritis.

Collagen molecules are very large and have a complex structure and so they cannot be absorbed when applied on the skin. Collagen peptide taken in through the mouth is broken down to amino acids by enzymes present in the stomach and intestinal juices. The amino acids obtained are further processed by other enzymes to metabolic intermediates that can have varied functions aside from the production of body proteins. Nonessential amino acids (amino acids not needed in the diet) such as glycine and proline, among others, can be synthesized in the body from metabolic intermediates obtained from non-protein and protein sources. Body proteins are produced from essential amino acids (amino acids needed in the diet; can be obtained from egg, meat, dairy products, soybean, etc.) and nonessential amino acids, through complicated biochemical processes as dictated by respective genes encoding the proteins. After biosynthesis, procollagen undergoes biochemical reactions during its conversion to collagen. Thus, there is no direct metabolic route from a collagen supplement to biochemically produced collagen. As such, collagen supplement is not necessarily a source of substances for the biochemical production of collagen that ultimately becomes part of body tissues.

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Dr. Elsie C. Jimenez, a biochemist and molecular biologist, is a professor emeritus at the University of the Philippines Baguio. She taught biochemistry for many years. Her research interests include protein chemistry, proteomics and toxinology. She also has interest in nutritional biochemistry and its applications to health and wellness. She can be reached at [email protected].