維生素.D

Description

     Vitamin D is a steroid hormone that exists in two molecular forms: vitamin D-3 (cholecalciferol) found in animal skin, and vitamin D-2 (ergocalciferol) found in yeast. These two forms are created by the action of the sun's ultraviolet rays on the biological precursors 7-dehydrocholesterol and ergosterol. Vitamin D is essential for calcium and phosphorus metabolism, and it is required for the normal development of bones and teeth

 

     Vitamin D can be acquired either by ingestion of preformed vitamin D or by the conversion of 7-dehydrocholesterol, after exposure to ultraviolet light. Ingested vitamin D is absorbed with the aid of bile. Vitamin D is then transported to the liver where it is converted into 25-hydroxycholecalciferol. This compound is transformed in the kidney into the physiologically active form 1,25-dihydroxycholecalciferol (1,25-DHCC). 1,25-DHCC is then transported to the intestinal mucosal cells, bone, and skeletal muscle where it is stored, regulating calcium absorption and mobilization. Vitamin D aids the absorption of calcium from the intestinal tract by stimulating the synthesis of calcium-binding protein in the intestinal mucous membrane. It also aids the resorption of phosphate in the renal tube. Vitamin D mobilizes phosphate from the bone to maintain serum phosphate levels, and stimulates the active phosphate transport.

     Vitamin A, choline, vitamin C, unsaturated fatty acids, and phosphorus assist absorption of vitamin D. Mineral oil or insufficient sunlight can prevent vitamin D absorption.

Properties and Uses

     Vitamin D's clinical application is in the treatment of rickets and osteomalacia. Rickets can be prevented in newborns by administering vitamin D in proper amounts early in, and throughout the growth period. If rickets do occur, large doses of the vitamin are given. Osteomalacia is prevented by adequate vitamin D, calcium, and phosphorus in the diet. Vitamin D must come from food, adequate sunlight, or concentrated supplements. The pain and weakness associated with vitamin D deficiency will usually disappear after one to two months of treatment.

 

Consequences of Deficiency

     Vitamin D deficiency creates a deficient deposition of hydroxyapatite in the bones. This is due to inadequate absorption of calcium from the intestinal tract, and from the retention of phosphorus in the kidney. This inadequate mineralization of the bones causes rickets in infants and children, and osteomalacia in adults. Rickets can cause delayed closure of the fontanelles, softening of the skull, soft fragile bones, enlargement of the wrist, knee, and ankle joints, poorly developed muscles, restlessness and nervous irritability. Delayed tooth development can be a sign of rickets. Some children develop rickets with vitamin D supplementation. This may be due to a genetic error in vitamin D metabolism, usually renal tubular dysfunction.

Insufficient sunlight can create vitamin D deficiency by preventing the conversion of 7-dehydrocholesterol to cholecalciferol. This type of deficiency is most common in countries with limited sunlight, or where the population dresses in a manner that reduces the sunlight exposure.

Toxicity Levels

     Vitamin D taken in excess can cause pathological changes in the body. Signs of vitamin D toxicity include excessive calcification of bone, kidney stones, calcification of soft tissue, headaches, weakness, nausea, vomiting, constipation, polyuria, and polydipsia.

 

Recommended Dietary Allowances

  • RDA for adult males: 200 IU
  • RDA for adult females: 200 IU
  • RDA for children 7 to 10 years: 200 IU
  • RDA for infants: 200 IU
  • RDA for pregnant and lactating women: 200 IU

     Difficulties in establishing requirements for vitamin D arise from the limited number of food sources available, lack of knowledge of precise body needs, and degree of synthesis in the skin by irradiation. The amount needed can vary between winter and summer in northern climates. In addition, life-style determines the degree of exposure to sunlight and would therefore influence individual need. This is especially true of the elderly and invalids who do not go outside and therefore may need supplementary vitamin D. Growth demands in childhood, during pregnancy, and during lactation necessitate increased intake.

     The daily recommendation for young adults is 7.5 mcg and older adults 5.0 mcg. The RDA standard is 10 mcg, or 400 international units (IU), of cholecalciferol daily for children and for women during pregnancy and lactation. One IU of vitamin D is equivalent to biologic activity of 0.025 mcg of pure crystalline vitamin D-3 (cholecalciferol).

     Adults over 22 years of age need only a small amount of vitamin D. Under normal circumstances their need is met by the vitamin D contained in an ordinary mixed diet and by exposure to sunlight. Adults who work at night and those whose clothing or living customs shield them from sunlight need somewhat more vitamin D in their diet.

No extra benefit is obtained from taking more than 400 IU daily except for therapeutic reasons; then, dosages can range from 1,500 to 2,800 IU daily.

Food Sources

· Fish Liver Oils · Egg Yolk · Herring · Kippers · Lard

· Mackerel · Salmon · Sardines · Shrimp · Tuna

 

Summary Deficiency Symptoms

· Rickets In Children
· Soft Fragile Bones
· Enlarged Joints
· Bowed Legs
· Deformation of Bones In:
· Chest

Spinal Cord
· Pelvis
· Tetanic Convulsions In Infants
· Osteomalacia In Adults
· Inability of the Body to Metabolize Calcium

 

 

Chemistry of Vitamin D

     The structures of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) and their provitamins are presented in Figure 1 on the right. Vitamin D is a generic term and indicates a molecule of the general structure shown for rings A, B, C, and D with differing side chain structures. The A, B, C, and D ring structure is derived from the cyclopentanoperhydrophenanthrene ring structure for steroids. Technically vitamin D is classified as a seco-steroid. Seco-steroids are those in which one of the rings has been broken; in vitamin D, the 9,10 carbon-carbon bond of ring B is broken, and it is indicated by the inclusion of "9,10-seco" in the official nomenclature.

 

 

 

     Vitamin D (calciferol) is named according to the revised rules of the International Union of Pure and Applied Chemists (IUPAC). Because vitamin D is derived from a steroid, the structure retains its numbering from the parent compound cholesterol. Asymmetric centers are designated by using the R,S notation; the configuration of the double bonds are notated E for "entgegen" or trans, and Z for "zuzammen" or cis. Thus the official name of vitamin D3 is 9,10-seco(5Z,7E)-5,7,10(19)cholestatriene-3-ol, and the official name of vitamin D2 is 9,10-seco(5Z,7E)-5,7,10(19), 22-ergostatetraene-3-ol.

     Vitamin D3 can be produced photochemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol which is present in the epidermis or skin of most higher animals. The chief structural prerequisite of a provitamin D is that it be a sterol with a 5,7 diene double bond system in ring B (Figure 2 to the left). The conjugated double bond system in this specific location of the molecule allows the absorption of light quanta at certain wavelengths in the UV range; this can readily be provided in most geographical locations by natural sunlight (or UV-B). This initiates a complex series of transformations ( partially summarized above in Fig.1) that ultimately results in the appearance of vitamin D3. Thus, it is important to appreciate that vitamin D3 can be endogenously produced and that as long as the animal (or human) has access on a regular basis to sunlight there is no dietary requirement for this vitamin.

 

Figure 1. Structural relationship of vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) with their respective provitamins, cholesterol, and a classic steroid hormone, cortisol (see inset box). The two structural representations presented at the bottom for both vitamin D3 and vitamin D2 are equivalent; these are simply different ways of drawing the same molecule. It is to be emphasized that vitamin D3 is the naturally occurring form of the vitamin; it is produced from 7-dehydrocholesterol, which is present in the skin, by the action of sunlight (see Figure 2). Vitamin D2 (which is equivalently potent to vitamin D3 in humans and many mammals, but not birds) is produced commercially by the irradiation of the plant sterol ergosterol with ultraviolet light.

 

Figure 2: Photochemical pathway of production of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol. The starting point is the irradiation of a provitamin D, which contains the mandatory 5,7-conjugated double bonds; in the skin this is 7-dehydrocholesterol. After absorption of a quantum of light from sunlight (UV-B), the activated molecule can return to the ground state and generate at least six distinct products. The four steroids that do not have a broken 9, 10-carbon bond (provitamin D, lumisterol, pyrocalciferol, and isopyrocalciferol) represent the four diastereomers with either an - or -orientation of the methyl group on carbon-10 and the hydrogen on carbon-9. The two secosteroid products, vitamin D3, previtamin D3, and tachysterol3 have differing positions of the three conjugated double bonds. In the skin, the principal product is previtamin D3, which then undergoes a 1,7-sigmatropic hydrogen transfer from C-19 to C-9, yielding the final vitamin D3: Vitamin D3 can be drawn as either a 6-s-trans representation or as 6-s-cis representation depending upon the state of rotation about the 6,7-single bond. The resulting vitamin D3, which is formed in the skin, is removed by binding to the plasma transport protein, the vitamin D-binding protein (DBP), present in the capillary bed of the dermis. The DBP-D3 then enters the general circulatory system.

 

Biochemistry and Physiology of Vitamin D

     A detailed study of the biochemical mode of action of the fat-soluble vitamin D was not possible until the availability in the 1960s of preparations of high specific activity radioactive vitamin D. As a consequence of efforts in several laboratories a new model emerged to describe the biological mechanisms of action of vitamin D3. This model is based on the concept that, in terms of its structure and mode of action, vitamin D is similar to the classic steroid hormones, e.g. aldosterone, testosterone, estradiol, progesterone, cortisol, and ecdysterone.

     The concept of the existence of the vitamin D endocrine system is now firmly established.

     The elements of the vitamin D endocrine system include the following:

(a) In the skin, photoconversion of 7-dehydrocholesterol to vitamin D3 or dietary intake of vitamin D3.

(b) Metabolism of vitamin D3 by the liver to 25(OH)D3, which is the major form of vitamin D circulating in the blood compartment.

(c) Conversion by the kidney of 25(OH)D3 [functioning as an endocrine gland] to produce the two principal dihydroxylated metabolites, namely 1,25(OH)2D3 and 24R,25(OH)2D3.

(d) Systemic transport of the dihydroxylated metabolites 1,25(OH)2D3 and 24R,25(OH)2D3 to distal target organs.

(e) Binding of the dihydroxylated metabolites, particularly 1,25(OH)2D3, to a nuclear receptor at the target organs followed by the subsequent generation of appropriate biological responses.

 

 

     An additional key component in the operation of the vitamin D endocrine system is the plasma vitamin D binding protein (DBP) that carries vitamin D3 and all of its metabolites to their various target organs.

     Over the past 25 years, research efforts have largely focused upon understanding how 125(OH)2D3 generates biological responses; an enormous scientific literature of over 5,000 scientific papers exists on this subject. By comparison, the biological actions of 24R,25(OH)2D3 have been relatively less studied. However, evidence has been presented to support the view that the combined presence of both 125(OH)2D3 and 24R,25(OH)2D3 are required to generate the complete spectrum of biological responses attributable to the parent vitamin D.

Metabolism of Vitamin D3

     Thus, vitamin D3 is, in reality, a prohormone and is not known to have any intrinsic biological activity itself. It is only after vitamin D3 is metabolized, first into 25(OH)D3 in the liver, and then into 125(OH)2D3 and 24R,25(OH)2D3 by the kidney, that biologically active molecules are produced. In toto some 37 vitamin D3 metabolites have been isolated and chemically characterized.

    The key kidney enzymes, the 25(OH)D3-1-hydroxylase and the 25(OH)D3-24-hydroxylase, as well as the liver vitamin D3-25-hydroxylase, are all known to be cytochrome P-450 mixed-function oxidases. Both of the renal enzymes are localized in mitochondria of the proximal tubules of the kidney. Mixed-function oxidases use molecular oxygen as the oxygen source instead of water. Mitochondrial mixed-function oxidases are composed of three proteins that are integral components of the mitochondrial membrane; they are renal ferredoxin reductase, renal ferredoxin, and cytochrome .

     The most important point of regulation of the vitamin D endocrine system occurs through the stringent control of the activity of the renal 1-hydroxylase. In this way the production of the hormone 125(OH)2D3 can be modulated according to the calcium and other endocrine needs of the organism. The chief regulatory factors are 125(OH)2D3 itself, parathyroid hormone (PTH), and the serum concentrations of calcium and phosphate. Probably the most important determinant of the 1-hydroxylase is the vitamin D status of the animal. When circulating concentrations of 125(OH)2D3 are low, production of 25(OH)2D3 by the kidney is high, and when circulating concentrations of 1,25(OH)2D3 are high, the output of 1,25(OH)2D3 by the kidney is sharply reduced.

     The regulation of gene transcription by 1,25(OH)2D3 is known to be mediated by interaction of this ligand with a nuclear receptor protein, termed the VDR. The tissue distribution of the VDR is known to occur in over 30 different cell types. In addition 1,25(OH)2D3 and the VDR are known to regulate the independent transcription of numerous proteins. A number of excellent articles have appeared describing our current understanding of how the VDR regulates gene transcription.

     The regulation of gene transcription by 1,25(OH)2D3 is known to be mediated by interaction of this ligand with a nuclear receptor protein, termed the VDR. The tissue distribution of the VDR is known to occur in over 30 different cell types. In addition 1,25(OH)2D3 and the VDR are known to regulate the independent transcription of numerous proteins. A number of excellent articles have appeared describing our current understanding of how the VDR regulates gene transcription.

Disease and Vitamin D

     The presents a schematic diagram of the metabolic processing of vitamin D via its endocrine system. Listed under each of the various metabolic or regulatory sites are disease states that are known to be clinically focused at that particular locus. Conceptually, human clinical disorders related to vitamin D can be considered as those arising because of (a) altered availability of vitamin D; (b) altered conversion of vitamin D3 to 25(OH)D3; (c) altered conversion of 25(OH)D3 to 1,25(OH)2D3 and/or 24R,25(OH)2D3; (d) variations in end organ responsiveness to 1,25(OH)2D3 or possibly 24R,25(OH)2D3; and (e) other conditions of uncertain relation to vitamin D. (e) other conditions of uncertain relation to vitamin D. Thus, the clinician/nutritionist/biochemist is faced with a problem, in a diagnostic sense, of identifying parameters of hypersensitivity, antagonism, or resistance (including genetic aberrations) to vitamin D or one of its metabolites as well as identifying perturbations of metabolism that result in problems in production and/or delivery of the hormonally active form, 1,25(OH)2D3.

 

 

A detailed consideration of this area is beyond the scope of this presentation. There are many scientific publications and only a few recent summary articles are listed at the end of this presentation

 

 

 

Drug Forms of 1,25(OH)2D3

     As a consequence of the significant scientific advances in the understanding of how vitamin D generates biological responses [principally via 1,25(OH)2D3], a number of new drug forms of 1,25(OH)2D3 have been generated by pharmaceutical companies. The table below summarizes these new drugs and the relevant pharmaceutical company, and identifies the clinical circumstance for which their use has been authorized.

 

The exploitation is in skin care products

     Include Vitamin D2(the calcify wheat corn solid Chun), Vitamin D3(the calcify cholesterol), all can be dissolved in a grease in, don't be dissolved in a water, is oxidized not easily, heat, alkali, influence.The vitamin D is produce surfeit most easily or the security top worry of vitamin, because it is responsible for the absorption calcium quality from the bowel way, long-term and big the usage for measuring can cause soft built-up calcify.Generally we can pass just the right amount of sunlight irradiation and acquire, but because of now person the busy life and living environment, more seldom seen go to sunlight, usually cause the vitamin D content inside the body lack of.BE particularly some stop menstruating behind of the calcium quality in women's skeleton compare to run off easily, should add just the right amount of vitamin D to help the absorption of the calcium inside the body, preventing a bone soft disease from.  

     Lack of the vitamin D, will there is serious influence for growth of the skeleton, the skeleton becomes flection and splits easily, will also make the tooth become weak.The influence that lacks of the vitamin D for the skin is to cause skin inflammation and fester easily etc. condition of illness.The vitamin D excess then will cause condition of illnesses, such as afferent calcify and the skin Yang...etc..

     The vitamin D and the skin hairdressing's also having very a toll-gate is, it can repress the erythema formation, can also cure psoriasis, bald-headed, the skin tubercle etc..Body inside lack of the vitamin D, the skin festers easily.The vitamin D3 can be used for curing psoriasis, the psoriasis is a kind of chronic skin disease, its clinical token mainly for last the skin cell increase to get, the excrescent keratin turn and the inflammation phenomenon of the epidermis cell.The psoriasis can't cure for good, only can repress an outbreak and ease condition of illness as far as possible, the vitamin D3 is currently to apply.

     The live metabolism outcome of the vitamin D3 has a function of adjusting the blood calcium, the blood Lin and stability skeleton in the body, the Morimoto waited for someone to use the live vitamin D3 treatment patient's bone soft in 1985, stumbling on a patient to get in the meantime of the psoriasis symptom also is alleviated, wasing proven by the follow-up research the live vitamin D3 also has the anti- psoriasis function, the live vitamin D3 resists the machine of the psoriasis to turn and mainly can be divided into three aspects:A, repress the keratin cell to increase to get, the live vitamin D3 is combined by body and represses the keratin cell to increase to get excessively with the top of the cell nucleus specially after entering the keratin cell.Two, promote plain maturity of keratin, the live vitamin D3 can make just the right amount of calcium enter the keratin cell, promoting the cell carry on normally of the keratin turn.Three, anti- inflammation function:The live vitamin D3 can make to be used for lymphoid ball, neutral ball of lymphoid ball, B of T and huge love cell, repress T- The cell increases to get and continues of the inflammation respond.

     A lot of cosmetics company the manufacturer will also impose the vitamin D concert vitamin A, E product in, make on all sides skin of the product moment tightly solid eyelid and eyes, stimulate the rebirth of the skin cell, rebuild to have an elastic leather layer, improve to comfort current thin Wen, crease, gestation Wen and prevent from freshman of thin Wen, increase skin of flexibility, protect a skin to strengthen a resistibility.There is very good result to the gestation Wen, crease, thin Wen, the fish tail Wen.