Proteins of the skin

Presland, R. B., and Dale, B. A. (2000). Epithelial structural proteins of the skin and oral cavity Function in health and disease. Crit. Rev. Oral Biol. Med. 11, 383-408. 

The use of sulfur mustard as a vesicant CW agent implies that proteins of the skin are a primary target. It was found that upon exposure of human callus to [14C]sulfur mustard, a significant part of the radioactivity was covalently bound to keratin (30). Most of the radioactivity (80%) bound to keratin could be removed by treatment with alkali, indicating the presence of adducts to glutamic and/or aspartic acid residues. 

In both cases, intramolecular displacement of the chloride leaving group by the sulfur atom—or, as we should call it, participation by sulfur (see Chapter 37)—gives a three-membered cyclic sulfonium ion intermediate (an episulfonium or thiiranium ion). Nucleophilic attack on this electrophilic sulfonium ion, either by water or by the structural proteins of the skin, is very fast. Of course, mustard gas can react twice in this way. You will see several more examples of reactions in which a sulfonium ion intermediate acts as an electrophile in the next section. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Administration of protein substrates (amino acids) may result in nausea, fever, flushing of the skin, metabolic acidosis or alkalosis, and decreased phosphorus and calcium blood levels. 

FIGURE 8.46 Hyaluronic acid has the consistency of a soft gel. It absorbs water easily and bonds with the proteins in the skin, making it useful in the repair of wounds and joint injuries. 

Because of the risks of adverse reaction to the vaccine by persons who had already been exposed to the disease a sensitivity test must be carried out prior to immunization with BCG. A Mantoux skin test assesses an individual s sensitivity to a purified protein derivative (PPD) prepared fi om heat-treated antigens (tuberculin) extracted fiom M tuberculosis. A positive test imphes past infection or past, successful immunization Those with strongly positive tests may have active disease and should be referred to a chest clinic. Many people with active TB, especially disseminated TB, however, sero-convert fiom skin test positive to skin test negative. Results of the skin test must therefore be interpreted with care. 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

Leather is the material made from animal skin by the process of tanning, which entails chemically altering the composition of the skin so as to make it durable and resistant to decay. Leather is therefore not a protein but a protein derivative. Although the tanning process alters the composition of skin, leather retains the fibrous structure and utilitarian functionality that make skin suitable for multifarious applications. Shelter, clothing, and decorative objects made from leather are, unlike skin or hide, stable to physical, chemical, and biological decay under dry or wet conditions (O Flaherty et al. 1965 ... 

This order might provide the genetic code for the formation of, say, a protein in the skin collagen of a human being. At the same location in the DNA molecule of another human the order of the bases may be only slightly different, such as... 

Biosynthesis as a tandemly repetitive polypeptide which is cleaved into multiple functionally similar proteins is highly unusual, and the only similar examples are the filaggrins of the skin of mammals (Rothnagel and Steinert, 1990). The reason why NPAs and filaggrins are produced in this way remains obscure. If a protein needs to be produced in large quantities rapidly, then a polyprotein would seem advantageous, but it seems inefficient for a genome to encode multiple copies of a protein when one will do, and other abundantly produced proteins are produced in the conventional... 

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