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Copper and Its Role in Collagen Development

By: Michael Q. Pugliese
Posted: May 30, 2014, from the June 2014 issue of Skin Inc. magazine.
Copper and Its Role in Collagen Development

In the development of professional skin care products, the ingredients selected by the cosmetic chemist are impacted by the discovery of new raw material technologies, and their ability to enhance or work synergistically with the reliable, proven and popular ingredients that provide desirable results. It has been said that old becomes new again, and nowhere is this more evident than in the category of peptides. As new peptides have been embraced by the skin care professional, information will be added to the discussion about a new use and, perhaps, usefulness, of copper, a cosmetic ingredient that has been around since the time of Nefertiti herself.

Brief history

Copper was one of the first metals used in cosmetics in ancient Egypt. Copper oxide is a green compound, known as malachite, initially used as an eye shadow. Lead sulfide, known as galena, was used to produce the color black. There is little in the written history of cosmetics that shows copper being used for anything other than makeup, although it was used medically in the treatment of certain conditions. For hundreds of years, copper and copper compounds have been used empirically by experimenting with treatment of a variety of diseases. There is mention of the use of copper in the Ebers papyrus, one of the oldest medical manuscripts in the world. The 20th century saw no other use for copper compounds until scientists isolated a sequence of amino acids (glycyl-L-histadyl-L-lysine (GHL-Cu)—a peptide) in a human serum that bound copper. In 1973, Loren Pickart, PhD, who was studying the biochemistry and physiology of aging, found that the copper peptide GHL-Cu was abundant in young people, but present in much lower levels in older people. Throughout the next 10 years, he worked to establish many favorable properties of the copper tripeptide. In 1983, Pickart applied for a number of patents in the area of wound-healing and hair growth. An interest in wound-healing was soon tied to the role of copper in the synthesis of both elastin and collagen.

Collagen synthesis

The synthesis of collagen is quite complex, but a key enzymatic reaction involves copper and the enzyme lysyl oxidase. Lysyl oxidase is an extracellular copper enzyme that catalyzes the formation of aldehydes from lysine residues in collagen and elastin precursors. Being highly reactive, they undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This action forms the basis of the crosslinking of collagen and elastin, an essential process for the stabilization of collagen fibrils, and for the integrity and elasticity of mature elastin. There are other complex crosslinks, some formed in collagen (pyridinolines derived from three lysine residues) and some in elastin (desmosines derived from four lysine residues) that differ in structure. The absence of crosslinking results in lathyrism, which is characterized by poor bone formation and strength, hyperextensible skin and weak ligaments.

Collagen, the main structural protein of connective tissue, is the most abundant tissue in animals—including humans—comprising 25–35% of whole-body protein content. The name “collagen” comes from the Greek kolla meaning “glue” with the suffix -gen denoting “producing.” The fibroblast is the most common cell that creates collagen. Collagen occurs in many places throughout the body. Although 28 types of collagen have been identified, more than 90% of the collagen in the body is type I.

The five most common types of collagen are:

  • Collagen I—found in skin, tendons, vascular ligatures and organs, is the main component of the organic part of bone, while calcium is the mineral part;
  • Collagen II—the main component of cartilage;
  • Collagen III—a reticulate, commonly found alongside type I;
  • Collagen IV—essential for binding the epidermis to the dermis as it forms the basal lamina, the epithelium-secreted layer of the basement
    membrane; and
  • Collagen V—found on and in cell surfaces, hair and placenta.

Copper peptides