Vitamin C Deficiency-Scurvy

Although there is no specific site of vitamin C storage in the body, signs of deficiency do not develop until previously adequately nourished subjects have been deprived of the vitamin for 4 to 6 months, by which time plasma and tissue concentrations have fallen considerably. 

The term scurvy is derived from the Italian scorbutica, meaning an irritable, neurotic, discontented, whining, and cranky person. The deficiency disease is certainly associated with listlessness and general malaise, and sometimes changes in personality and psychomotor performance and a lowering of the general level of arousal. The behavioral effects can presumably be attributed to impaired synthesis of catecholamines as a result of reduced activity of dopamine -hydroxylase (Section 13.3.1). 

Most of the other clinical signs of scurvy can be accounted for by effects of deficiency on collagen synthesis as a result of impaired proUne and lysine hydroxylase activity (Section 13.3.3). 

In general, the effects on collagen synthesis are more marked and more important than those of decreased formation of carnitine (as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases Section 14.1.1), impaired xenobiotic metabolism, or hypercholesterolemia (Section 13.3.8). However, depletion of muscle carititine may account for the lassitude and fatigue that precede clinical signs of scurvy. 

Vascular fragility may also result from reduced sulfation of proteoglycans in connective tissue, as may also occur in hyperhomocysteinemia (Section 10.3.4.2). Dehydroascorbate catalyzes the oxidation of homocysteine to ho-mocysteic acid, which is the precursor of PAPS, the sulfate donor for sulfation reactions (McCuUy, 1971). 

In general, the effects on collagen synthesis are more marked and more important than those of decreased formation of carnitine (as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases Section 

impaired xenobiotic metabolism, or hypercholesterolemia (Section 13.3.8). However, depletion of muscle carnitine may account for the lassitude and fatigue that precede clinical signs of scurvy. 

Wounds show only superficial healing in scurvy with little or no formation of (collagen-rich) scar tissue, so thathetdingis delayed and wounds can readily be reopened. The scorbutic scar tissue has only about htdf the tensile strength of that normtdly formed. 

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Deficiency symptoms In vitamin C deficiency scurvy develops. It is characterized by ecchymosis, petechiae, swollen and bleeding gums, subperiosteal haemorrhage, bones are painful to touch, impaired wound healing, anaemia, loosening of teeth and gingivitis. 

In this period, the empirical healing of certain diseases by foods was estabUshed. Examples (3) were the treatment of night blindness (vitamin A deficiency) with hver ia many cultures over centuries, of beriberi (vitamin deficiency) by use of unpoHshed rice by the Japanese navy, of scurvy (vitamin C deficiency) by citms fmits ia the British navy or piae needle extracts by North American natives, and pellagra (niacia deficiency) by a dietary shift away from corn-based foods ia many countries. Other, nondietary empirical treatments iavolved, eg, exposure of children ia northern latitudes to sunlight to cute tickets (vitamin D deficiency) (4). 

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. 

In addition to the hazards of weather, participants in early polar expeditions often suffered from scurvy, caused by a dietary vitamin C deficiency. 

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. 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

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. 

This of course goes a long way to explaining the association of scurvy with vitamin C deficiency, and the successful utilization by the British navy of lime juice as a means of prevention of the disease - hence the expression limey for British sailors. 

If one reads an account of the outbreak of scurvy on shipboard in the days of long voyages on sailing vessels, he finds indications of individual differences in vitamin C need. For example, in Dana s Two Years before the Mast, one member of the crew was described as suffering from severe scurvy and was about to die of the disease, while many of the crew were quite free from any symptoms. Since they had been living for the same length of time on vitamin C-deficient diets, they would, if uniformly constituted, have all been attacked at about the same time. 

With respect to human beings there is some question as to what level of tissue saturation should ideally be maintained. In guinea pigs defects in developing incisors appear when the tissue concentrations are about 40 per cent of the maximum. Scurvy symptoms do not appear until the tissue saturation has reached a much lower level (about 20 per cent saturation). It seems logical to suppose that in different individuals the manifestations of mild vitamin C deficiency would be different and that a high degree of saturation would be safest from the standpoint of all the vulnerable tissues. 19... 

Selected prolines and lysines are hydroxylated by prolyl and lysyl hydroxylases. These enzymes, located in the RER, require ascorbate (vitamin C), deficiency of which produces scurvy. 

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. 

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. 

The deficiency state scurvy is characterized by degenerative changes in the capillaries, bone, and connective tissues. Mild vitamin C deficiency symptoms may include faulty bone and tooth development, gingivitis, bleeding gums, and loosened teeth. 

The answer is B. The patient shows many signs of vitamin G deficiency or scurvy, which is seen most frequently in infants, the elderly, and in alcoholic patients. Particularly indicative of vitamin C deficiency are the multiple small hemorrhages that occur under the skin (petechiae) and nails and surrounding hair follicles. Bleeding gums are a classic indicator of scurvy. 

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. 

The knowledge of some vitamins reaches back into folk medicine North American aboriginal peoples treated scurvy (later recognized as vitamin C deficiency) with cedar leaf tea (Thuja), and, from the seventeenth century on, the British Navy issued lime... 

It is indicated for treatment of scurvy, for prophylaxis of vitamin C deficiency, to acidify urine, anaemia of vitamin C deficiency, as antioxidant to protect natural colour and flavour of many foods, dental caries and increased capillary fragility. 

Scurvy remains a problem today. The malady is still encountered not only in remote regions where nutritious food is scarce but, surprisingly, on U.S. college campuses. The only vegetables consumed by some students are those in tossed salads, and days go by without these young adults consuming fruit. A 1998 study of 230 students at Arizona State University revealed that 10% had serious vitamin C deficiencies, and 2 students had vitamin C levels so low that they probably had scurvy. Only half the students in the study consumed the recommended daily allowance of vitamin C. 

Evidence for vitamin C deficiency in prematurely born infants showing hyperamino aciduria has been reported by Dustin and Bigwood (D29). In addition to the increased excretion of certain amino acids reported in common rachitis, there is also an increased output of tyrosine and phenylalanine in scurvy (Jll). The blood levels of amino acids are normal (H28). The excessive output of tyrosine and phenylalanine is considered to be related to a renal factor it is not a competitive effect due to increased excretion of serine and threonine (J13). In addition, therefore, to the increased output of certain amino acids reported in common rachitis (vide infra) there is also, in scurvy, an increased excretion of tyrosine and phenylalanine. 

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. 

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. 

AO/FRS - scavenges DPPH, nitrite (NO -), OH, 02 02-, ONOO- regenerates a-Tocopherol from a-Tocopheryl radical antiageing nutriceutical vitamin C-deficiency disease scurvy cured by lime juice — found by Dr James Lind promoted by Captain James Cook in British navy (18th century) — hence limeys Dr Lind befriended poet Percy Shelley was thence the source for Frankenstein or The Modern Prometheus by Mary Wollstonecrafi Shelley... 

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