Collagen Copper

Oxidative coupling of collagen Copper lysine oxidase (animals)... 

Calcium Carbonate Calcium Hydroxide Calcium Oxide Calcium Phosphate Calcium Silicate Calcium Sulfate Camphor Carbon Dioxide Carbon Monoxide Cellulose Cellulose Nitrate Cellulose Xanthate Chlorophyll Cholesterol Cinnamaldehyde Citric Acid Collagen Copper(I) Oxide Copper(II) Oxide Copper(II) Sulfate Cyanoacrylate Cyanocohalamin Denatonium Benzoate Dimethyl Ketone Ethyl Acetate Ethyl Alcohol Ethylene Glycol Ethylene Oxide... 

C30-50 alcohols Cellulose diacetate 2-Chloroacrylonitrile Collagen Copper Corn (Zea mays) starch C20-40 pareth-3 C20-40 pareth-40 C30-50 pareth-3 C30-50 pareth-10... 

Tom, K., M. Chen, W. Goettlich-Riemann, J. Tanimoto, S. Grey, D. Wake, and R.E. Rucker. 1977. Collagen and elastin metabolism in relation to dietary zinc and copper in the chick and rat. Nutr. Rep. Inter. 15 191-198. 

Collagen molecules assemble into fibrils. Cross-linking involves lysyl oxidase, an enzyme that requires and copper. 

Copper is a component of many enzymes including amine oxidase, lysyl oxidase, ferroxidase, cytochrome oxidase, dopamine P-hydroxylase, superoxide dismutase and tyrosinase. This latter enzyme is present in melanocytes and is important in formation of melanin controlling the colour of skin, hair and eyes. Deficiency of tyrosinase in skin leads to albinism. Cu " ion plays an important role in collagen formation. 

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

Mechanism of Action A heavy metal antagonist that chelates copper, iron, mercury, lead to form complexes, promoting excretion of copper. Combines with cystine-forming complex, thus reducing concentration of cystine to below levels for formation of cystine stones. Exact mechanism for rheumatoid arthritis is unknown. May decrease cell-mediated immune response. May inhibit collagen formation. Therapeutic Effect Promotes excretion of copper, prevents renal calculi, dissolves existing stones, acts as anti-inflammatory drug. 

Crosslinking of collagen is initiated by oxidation of some of the lysyl and hydroxylysyl side chains from amino groups to aldehyde groups under the action of a copper-containing oxidase (Eq. 8-8, Chapter 18). The aldehyde groups enter into a variety of reactions that... 

Lysine tyrosylquinone (LTQ). Another copper amine oxidase, lysyl oxidase, which oxidizes side chains of lysine in collagen and elastin (Eq. 8-8) contains a cofactor that has been identified as having a lysyl group of a different segment of the protein in place of the - OH in the 2 position of topaquinone.465 Lysyl oxidase plays an essential role in the crosslinking of collagen and elastin. 

Collagen - [FOOD ADDITIVES] (Vol 11) - [PROTEINS] (Vol 20) -m animal hides [LEATHER] (Vol 15) -as cell microcarrier [CELL CULTURE TECHNOLOGY] (Vol 5) -effect of copper on [MINERAL NUTRIENTS] (Vol 16) -gelatin from [GELATIN] (Vol 12) -sumres of [SUTURES] (Vol 23)... 

Copper is an essential component of numerous key metalloenzymes which are critical in melanin formation, myelin formation and crosslinking of collagen and elastin. Copper plays a vital role in hemopoiesis, maintenance of vascular and skeletal integrity, and structure and function of the nervous system. Thus a deficiency of copper can lead to a variety of adverse effects such as increased fragility in bones, aneurysm formation in arteries and a loss of lysyl oxidase activity in cartilage.54 57 Articles on copper also appear in Siget1, volumes 3 and 5, all of volumes 12 and 13, and volume 14,... 

In in vitro studies penicillamine inhibited angiotensin-con-verting enzyme (ACE) and carboxypeptidase (930). Penicillamine interferes with the functions of the copper-containing enzyme ceruloplasmin, and some of the penicillamine- and copper-containing complexes formed in vivo have a superoxide dismutase effect (931). In patients with scleroderma, penicillamine normalized collagen metabolism, by inhibiting beta-galactosidase activity (932). 

Copper is required for the activity of enzymes associated with iron metabolism, elastin and collagen formation, melanin production and the integrity of the central nervous system. It is required with iron for normal red blood cell formation. Copper is also required for bone formation, brain cell and spinal cord structure, the immune response and feather development and pigmentation. A deficiency of copper leads to poor iron mobilization, abnormal... 

Covalent cross-links both between and within the tropocollagen molecules confer strength and rigidity on the collagen fiber. These cross-links are formed between Lys and its aldehyde derivative allysine. Allysine is derived from Lys by the action of the copper-containing lysyl oxidase which requires pyridoxal phosphate for activity. The disease lathyrism is caused by the inhibition of lysyl oxidase by the chemical (3-aminopropionitrile in sweet pea seeds, and results in defective collagen due to the lack of cross-links. 

These agents bind the copper so that it is solublized and excreted in the urine. They are effective because of their high affinity for copper(II) over other metals in the body. Although both isomers of penicillamine bind copper equally well it has been found that the L-form is toxic. Interestingly D-penicillamine is also used to treat rheumatoid arthritis where it acts to reduce collagen crosslinking the enzymes responsible for this process are largely copper centred. 

Copper deficiency, not iron deficiency, produces inadequate cross-linking in collagen. 

---