Keratins

The important molecules synthesized by the skin include keratin, melanin, collagen and glycosaminoglycans.

Keratins are high-molecular-weight polypeptide chains produced by keratinocytes (Fig. 1). They are the major constituent of the stratum corneum, hair and nails. The stratum corneum comprises 65% keratin (along with 10% soluble protein, 10% amino acid, 10% lipid and 5% cell membrane).

Fig. 1 Molecular structure of alpha-keratin.

The molecule forms a helical coil which, if stretched, unwinds irreversibly to produce the beta form. The covalent bonds linking the cystine molecules provide extra strength.

From J Invest Dermatol 2001: 116; 964–969, with permission of Blackwell Publishing.

Keratin proteins are of varying molecular weight (between 40 and 67 kDa). Different keratins are found at each level of the epidermis, depending on the stage of differentiation. Epidermal keratin contains less cystine and more glycine than the harder hair keratin.

Melanins

Melanin is produced from tyrosine (Fig. 2) in melanocytes and takes two forms:

Fig. 2 Biosynthesis of melanin.

Eumelanin is a high-molecular-weight polymer of complex structure formed by oxidative polymerization. The phaeomelanin polymer is synthesized from dopaquinone and cysteine (via cysteinyl dopa).

Most natural melanins are mixtures of eumelanin and phaeomelanin. Melanins act as an energy sink and as free radical scavengers, and absorb the energy of ultraviolet (UV) radiation.

Collagens

Collagens are synthesized by fibroblasts (Fig. 3) and are the major structural proteins of the dermis, forming 70–80% of its dry weight. The main amino acids in collagens are glycine, proline and hydroxyproline. Collagens are broken down, e.g. in wound healing, by collagenases, of which the matrix metalloproteinases are important. There are over 22 types of collagen; at least five are found in skin:

Fig. 3 Collagen production.

Tropocollagen is formed from three polypeptide chains that are coiled around each other in a triple helix. Assembled collagen fibrils are 100 nm wide, with cross-striations visible with electron microscopy every 64 nm.

Glycosaminoglycans (GAGs)

The ‘ground substance’ of skin is largely made up of GAGs, providing viscosity and hydration. In the dermis, chondroitin sulphate is the main GAG, along with dermatan sulphate and hyaluronan.

GAGs often exist as high-molecular-weight polymers with a protein core. These structures are known as proteoglycans (Fig. 4).

Fig. 4 Proteoglycan.

(a) Proteoglycan aggregate with central filament of hyaluronan. (b) Detailed view of proteoglycan monomer with protein core.

Skin surface secretions

The skin surface has a slightly acidic pH (between 6 and 7). Sebum (Table 1), sweat and the horny layer (including intercellular lipid) contribute to the surface conditions, which generally discourage microbial proliferation.

Table 1 Sebum and epidermal lipid composition

Subcutaneous fat

Triglyceride is synthesized from α-glycerophosphate and acyl coenzyme A (CoA). Triglyceride is broken down by lipase to give free fatty acid (FFA) – an energy source – and glycerol (Fig. 5).

Fig. 5 Metabolism of subcutaneous fat.

Hormones and the skin

The skin is the site of production of one hormone (vitamin D), but it is often a target organ for other hormones and is frequently affected in endocrine diseases (Table 2).

Table 2 Hormones and the skin

Hormone	Site of production	Effects
Vitamin D	Produced in the dermis from precursors though the action of UV radiation	Important for the absorption of calcium and for calcification
Corticosteroids	Adrenal cortex	Receptors on several cells in both epidermis and dermis Produce vasoconstriction Reduce mitosis by basal cells Generate anti-inflammatory effects on leucocytes Inhibit phospholipase A
Androgens	Adrenal cortex Gonads	Receptors on hair follicles and sebaceous glands Stimulate terminal hair growth and increased output of sebum
Melanocyte-stimulating hormone (MSH) Adrenocorticotrophic hormone (ACTH)	Pituitary gland	Stimulates melanogenesis
Oestrogens	Adrenal cortex Ovaries	Stimulate melanogenesis
Epidermal growth factor (EGF)	Skin (probably produced at several sites in, as well as outside, the skin)	Receptors found on keratinocytes, hair follicles, sebaceous glands and sweat duct cells Stimulates differentiation Alters calcium metabolism
Cytokines and eicosanoids	Cell membrane (may be produced by several skin cells, including keratinocytes and lymphocytes)	Effects on immune function, inflammation and cell proliferation

Web resource

http://www.ncbi.nlm.nih.gov/books/NBK22247/