Scurvy Collagen

One-third of the amino acid residues in collagen are Gly, while another quarter are Pro. The hydroxylated amino acids 4-hydroxyproline (Hyp) and 5-hydroxylysine (Hyl) are formed post-translationally by the action of proline hydroxylase and lysine hydroxylase. These Fe2+-containing enzymes require ascorbic acid (vitamin C) for activity. In the vitamin C deficiency disease scurvy, collagen does not form correctly due to the inability to hydroxylate Pro and Lys. Hyl residues are often post-translationally modified with carbohydrate. 

M.p. 190-192 C. The enolic form of 3-oxo-L-gulofuranolactone. It can be prepared by synthesis from glucose, or extracted from plant sources such as rose hips, blackcurrants or citrus fruits. Easily oxidized. It is essential for the formation of collagen and intercellular material, bone and teeth, and for the healing of wounds. It is used in the treatment of scurvy. Man is one of the few mammals unable to manufacture ascorbic acid in his liver. Used as a photographic developing agent in alkaline solution. 

Scurvy results from a dietary vitamin C deficiency and involves the inability to form collagen fibrils properly. This is the result of reduced activity of prolyl hydroxylase, which is vitamin C-dependent, as previously noted. Scurvy leads to lesions in the skin and blood vessels, and, in its advanced stages, it can lead to grotesque disfiguration and eventual death. Although rare in the modern world, it was a disease well known to sea-faring explorers in earlier times who did not appreciate the importance of fresh fruits and vegetables in the diet. 

The complex series of events in collagen maturation provide a model that illustrates the biologic consequences of incomplete polypeptide maturation. The best-known defect in collagen biosynthesis is scurvy, a result of a dietary deficiency of vitamin C required by... 

Silk fibroin and collagen illustrate the close linkage of protein stmcture and biologic function. Diseases of collagen mamration include Ehlers-Danlos syndrome and the vitamin C deficiency disease scurvy. 

C Ascorbic acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis antioxidant enhances absorption of iron Scurvy—impaired wound healing, loss of dental cement, subcutaneous hemorrhage... 

Signs of vitamin C deficiency in scurvy include skin changes, fragifity of blood capillaries, gum decay, tooth loss, and bone fracmre, many of which can be attributed to deficient collagen synthesis. 

Scurvy affects the structure of collagen. However, it is due to a deficiency of ascorbic acid (Chapter 45) and is not a genetic disease. Its major signs are bleeding... 

Diseases associated with impaired synthesis of collagen include scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome (many types), and Menkes disease. 

Answer E. The patient has many signs of scurvy from a vitamin C deficiency. The diet, which contains no fruits or vegetables, provides little vitamin C, Prolyl hydroxylase requires vitamin C, and in the absence of hydroxylation, the collagen a-chains do not form stable, mature collagen. The anemia may be due to poor iron absorption in the absence of ascorbate. 

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

The formation of Hyp and Hyl residues in procollagen is catalyzed by iron-containing oxygenases ( proline and lysine hydroxylase, EC 1.14.11.1/2). Ascorbate is required to maintain their function. Most of the symptoms of the vitamin C deficiency disease scurvy (see p. 368) are explained by disturbed collagen biosynthesis. 

Deficiency may occur in infants if no fruits or vegetables are added to their milk formulas. In alcoholics, and in elderly subjects who consume inadequate diets vitamin C deficiencies are frequent. Severe ascorbic acid deficiency is characterized by the syndrome known as scurvy. Its manifestations are generally based on a loss of collagen. Symptoms include hemorrhages, loosening of teeth. In children cellular changes in the long bones occur. 

In vitamin C avitaminosis, or scurvy, the joints become painful and the gums bleed and deteriorate, resulting in tooth loss. Gangrene and infections may also occur, and wounds do not heal properly. These symptoms all result from impaired collagen synthesis and... 

A deficiency of ascorbic acid results in scurvy, a disease character ized by sore, spongy gums, loose teeth, fragile blood vessels, swollen joints, and anemia (Figure 28.9). Many of the deficiency symptoms can be explained by a deficiency in the hydroxylation of collagen, resulting in defective connective tissue. 

Hydroxyproline and hydroxylysine result from the hydroxylation by specific hydroxylases of proline and lysine residues after their incorporation into a-chains. The enzymes require ascorbic acid as a cofactor. [Note An ascorbic acid deficiency results in scurvy.] The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosy lated (most commonly, glucose and galactose are added sequentially to the triple helix). 

Vitamin C is important to all animals, including humans, and is vital in the production of collagen. Collagen is important in the formation of connective tissues that give our body shape and help to support vital organs. Vitamin C prevents the disease scurvy. 

Co-substrate in the hydroxylation of proline in collagen Vitamin C (ascorbic acid) Scurvy... 

The well-known deficiency syndrome is scurvy. The initial changes are follicular keratosis on the upper arms, back, buttocks, and lower extremities, which are related to a defective collagen synthesis.28 This is followed by a purpuric follicular rash, swollen, bleeding gums, stomatitis, and epistaxis. Hematomas, especially painful subperiostal, may develop.29... 

It is conceivable that the reduced formation of tritiated water observed in scurvy could be due to a general reduction in protein synthesis, but this would not explain the marked differences between the specific activities of proline and hydroxyproline observed, nor would it explain observations in our laboratory that glycine and tyrosine are incorporated at rates similar to that of incorporation of proline into the collagen of granuloma obtained from scorbutic animals. 

The striking increases in the formation of tritiated water and tritiated hydroxyproline on in vitro addition of ascorbate are consistent with a function of this vitamin in hydroxylation—probably at step 3. The present results do not support a systemic ascorbic acid-mediated effect, the belief that ascorbic acid functions in the maintenance of collagen, or acts by stimulating maturation of the fibroblasts in the system under study here. The present data do not support the possibility that intermediates containing hydroxyproline accumulate in scurvy. The proposal that ascorbic acid is involved in the hydroxylation reaction itself is consistent with studies on the nonenzymatic hydroxylation of proline (4) and on enzymatic hydroxylation of other compounds (5, 20, 21, 44, 51). 

Ascorbic acid is a vitamin in primates. In most other animals, it can be synthesized by a branch of the glucoronic acid pathway (Chapter 18). It is apparently not changed into any coenzyme in the human being and participates as a vitamin in a reducing capacity in several biochemical reactions. These include the post-translational hydroxylation of proline in collagen biosynthesis (Chapter 8) and in tyrosine metabolism (Chapter 20). Ascorbic acid is oxidized to dehydroascorbic acid, a diketo derivative of ascorbate. Scurvy is a deficiency disease caused by a shortage of dietary ascorbic acid. In children, this results in defective bone formation in adults, extensive bleeding occurs in a number of locations. Scurvy is to be suspected if serum ascorbic acid levels fall below 1 jug/mL. 

In scurvy, vitamin C deficiency disease, hydroxylation of proline is defective, and the smaller hydroxyproline content of the collagen helix results in weaker hydrogen bonding. 

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