Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.
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PMID:The regulation of prostaglandin E1 formation: a candidate for one of the fundamental mechanisms involved in the actions of vitamin C. 39 Mar 31

Increasing knowledge concerning the molecular structure of collagen and the steps involved in its biosynthesis provides the basis for a new look at the collagen diseases. Some, like the Ehlers-Danlos syndrome, are now known to be the expression of primary molecular defects; others, such as scurvy and scleroderma, appear to be secondary to some process that disrupts normal controls over collagen synthesis or deposition.
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PMID:Collagen diseases and the biosynthesis of collagen. 92 26

Scurvy developed in a 56-year-old man with poor dietary intake and was associated with knee hemarthroses and synovial thickening. The synovial membrane showed interstitial hemorrhage and many large fibroblasts but little collagen and some disarray of vascular basement membrane. Hemarthroses and all knee symptoms completely resolved on a normal diet. To our knowledge, these are the first electron-microscopic studies of synovial membrane in human scurvy, and our findings support a defect in collagen synthesis as a factor in etiology.
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PMID:Scurvy and hemarthrosis. 94 90

The effect of vitamin C on the common cold has been the subject of several studies. These studies do not support a considerable decrease in the incidence of the common cold with supplemental vitamin C. However, vitamin C has consistently decreased the duration of cold episodes and the severity of symptoms. The benefits that have been observed in different studies show a large variation and, therefore, the clinical significance may not be clearly inferred from them. The biochemical explanation for the benefits may be based on the antioxidant property of vitamin C. In an infection, phagocytic leucocytes become activated and they produce oxidizing compounds which are released from the cell. By reacting with these oxidants, vitamin C may decrease the inflammatory effects caused by them. Scurvy, which is caused by a deficiency in vitamin C, is mostly attributed to the decreased synthesis of collagen. However, vitamin C also participates in several other reactions, such as the destruction of oxidizing substances. The common cold studies indicate that the amounts of vitamin C which safely protect from scurvy may still be too low to provide an efficient rate for other reactions, possibly antioxidant in nature, in infected people.
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PMID:Vitamin C and the common cold. 154 1

We have previously reported that scorbutic and fasted guinea pig sera contain an insulin-like growth factor-I (IGF-I)-reversible inhibitor of collagen, proteoglycan, and DNA synthesis in cultured cells. Here we report that IGF-binding protein (IGFBP) activity is increased in serum containing the inhibitor [125I]IGF-I or -II bound to these sera was eluted in the 30- to 50-kDa region of an S200 gel column. [125I]IGF-I affinity cross-linking analysis revealed that a 38-kDa cross-linked species increased markedly in fasted and scorbutic sera, with a lesser increase in a 34-kDa species, while scorbutic sera also yielded a 44-kDa species. Gel filtration of unlabeled sera showed a 10-fold increase in the activity of two proteins in the 30- to 50-kDa region from the experimental sera. Their activity correlated with their ability to inhibit binding of [125I]IGF-I to its cellular receptor, suggesting that they have the potential to inhibit IGF-I-dependent functions. Ligand blotting showed that 29 and 35-kDa IGFBPs were almost undetectable in normal serum, but were dramatically induced by scurvy and fasting, so that they accounted for close to 40% of the total circulating BPs. Total IGFBP-3 in the experimental sera was increased about 30%, while there was little effect of scurvy or fasting on the level of BP-3 activity isolated by acid extraction of the high mol wt region of the S200 column. An IGF-I analog with normal affinity for the 30- to 50-kDa BPs from fasted and scorbutic sera, but with reduced affinity for the cell receptor, was equivalent to IGF-I in reversing the inhibition of collagen synthesis by scorbutic guinea pig serum in human fibroblasts. Thus, reversal of inhibition appears to require initial saturation of IGFBPs. The overall results suggest that two circulating IGFBPs with unoccupied binding sites are induced in vitamin C-deficient or fasted guinea pigs and may be responsible for inhibition of IGF-I-dependent functions by sera from these animals.
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PMID:Elevated activity of low molecular weight insulin-like growth factor-binding proteins in sera of vitamin C-deficient and fasted guinea pigs. 170 59

Vitamin C deficiency is associated with defective connective tissue, particularly in wound healing. Ascorbate is required for hydroxylation of proline residues in procollagen and hydroxyproline stabilizes the collagen triple helical structure. Consequently, ascorbate stimulates procollagen secretion. However, collagen synthesis in ascorbate-deficient guinea pigs is decreased with only moderate effects on proline hydroxylation. Proteoglycan synthesis, which does not require ascorbate, also is decreased and both effects are correlated with the extent of weight loss during scurvy. Fasting, with ascorbate supplementation, produces similar effects. Both functions are inhibited in cells cultured in sera from either scorbutic or starved guinea pigs and inhibition is reversed with insulin-like growth factor (IGF)-I. The inhibitor appears to consist of two IGF-binding proteins induced during vitamin C deficiency and starving and may be responsible for in vivo inhibition of collagen and proteoglycan synthesis.
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PMID:Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. 172 May 97

When guinea pigs are fed tissue-saturating amounts of ascorbate, C1q concentrations are significantly higher than in those animals fed only enough ascorbate for adequate growth and for the prevention of scurvy. C1q is the recognition protein of the classical complement pathway, a system of blood proteins that constitutes an important part of host defense against pathogens. The observed effect of ascorbate nutriture on C1q concentrations is consistent with the known role of ascorbic acid in hydroxyproline biosynthesis. C1q is a hydroxyproline-containing protein with structural similarities to collagen.
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PMID:Complement component C1q activity and ascorbic acid nutriture in guinea pigs. 196 75

Ever since the discovery of vitamin C (ascorbic acid), scientists have been intrigued as to how ascorbic acid deficiency can lead to the diverse symptoms exhibited in scurvy. Only in recent years has it been appreciated that ascorbic acid has important functions in many cellular reactions and processes in addition to its role in collagen synthesis. The few such reactions that are understood at the molecular level make it apparent that ascorbic acid does not directly participate in enzyme-catalyzed conversion of substrate to product. Instead, the vitamin regenerates prosthetic metal ions in these enzymes in their required reduced forms. This is in agreement with other antioxidant functions of vitamin C, e.g., scavenging of free radicals. Ascorbate and other antioxidant nutrients are presumed to play a pivotal role in minimizing the damage from oxidative products, including free radicals. This protective function is twofold: the already-oxidized groups in prosthetic centers of enzymes are reduced and the oxidants and free radicals are removed.
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PMID:Vitamin C: newer insights into its biochemical functions. 205 41

It has long been suspected that ascorbic acid is involved in many cellular reactions. This is evident from the multitude of seemingly unrelated symptoms seen in scurvy. However, until recently, our understanding of its involvement was confined to its role in the synthesis of collagen. Studies in the past few years have unveiled mechanisms of its actions in collagen formation and many other enzymatic reactions. In addition, numerous physiological responses are reportedly affected by ascorbic acid. From the well-characterized enzymatic reactions involving ascorbic acid, it has become clear that in animal cells the ascorbate does not seem to be directly involved in catalytic cycles. Rather its major function seems to keep prosthetic metal ions in their reduced form. The role of ascorbate as a reductant in these enzymatic reactions complements its other antioxidant functions which have been recently appreciated, including that as a scavenger of free radicals. Therefore, it seems that the major function of ascorbate is to protect tissues from harmful oxidative products and to keep certain enzymes in their required reduced forms. However, it remains unclear how the deficiency of ascorbate leads to the pathological symptoms found in scurvy.
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PMID:Cellular functions of ascorbic acid. 226 11

Our recent studies suggested that decreased collagen synthesis in bone and cartilage of scorbutic guinea pigs was not related to ascorbate-dependent proline hydroxylation. The decrease paralleled scurvy-induced weight loss and reduced proteoglycan synthesis. Those results led us to propose that the effects of ascorbate deficiency on extracellular matrix synthesis were caused by changes in humoral factors similar to those that occur in fasting. Here we present evidence for this proposal. Exposure of chick embryo chondrocytes to scorbutic guinea pig serum, in the presence of ascorbate, led to effects on extracellular matrix synthesis similar to those seen in scorbutic animals. The rates of collagen and proteoglycan synthesis were reduced to approximately 30-50% of the levels in cells cultured in normal guinea pig serum plus ascorbate, but proline hydroxylation and procollagen secretion were unaffected. Similar results were obtained with serum from fasted guinea pigs supplemented in vivo with ascorbate. The growth rate of the chondrocytes was not significantly affected by scorbutic guinea pig serum.
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PMID:Decreased extracellular matrix production in scurvy involves a humoral factor other than ascorbate. 337 81


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