What Is Vitamin D Synthesis?

Vitamin D (VD for short) is a fat-soluble vitamin, which is a cyclopentane polyhydrophenanthrene compound. It is a group of vitamins that are structurally related to sterols and can prevent rickets. The most important are vitamins D3 and D2. The former is made from 7-dehydrocholesterol under the skin of human beings by ultraviolet irradiation. The latter is made of ergosterol contained in plants or yeasts by ultraviolet irradiation. The main function of vitamin D is to promote the absorption of calcium and phosphorus by small intestinal mucosal cells. Calcium absorption in the intestine requires a calcium-binding protein. 1,25-dihydroxyvitamin D3 can induce the synthesis of this protein, promote the absorption of Ca ²⁺ , and promote the regeneration of calcium salts and new bone formation. The reabsorption of calcium and phosphorus by tubule cells can increase blood calcium and blood phosphorus concentrations, which is conducive to new bone formation and calcification. ^[1]

In addition, vitamin D also promotes skin cell growth, differentiation, and regulates immune function. The average adult often comes in contact with sunlight to prevent deficiency, and infants, pregnant women, nursing mothers, and elderly people who do not go outdoors often increase the vitamin D supply to 10 g per day (equivalent to 400 international units). Children with vitamin D deficiency can suffer from rickets and adults with osteomalacia. ^[1]

Food sources are relatively high in fatty fish, animal liver, egg yolk, and cream, and cod liver oil is high in content. ^[1]

Chinese name: Vitamin D
Foreign name: vitamin D
Function: Promote calcium and phosphorus absorption, skin cell growth, differentiation and regulate immune function
Deficiency: Rickets in children and osteomalacia in adults

Main category: The main VDs are vitamin D3 and D2
To source: UV exposure and food sources
Food source: Relatively more in marine fish, animal liver, egg yolk and cod liver oil
Excessive illness: Hypercalcemia causes renal impairment and soft tissue calcification
Short name: VD

VD Vitamin D VD Introduction

As early as the early 1930s, scientists researched that extra sunlight or edible olive oil and linseed oil exposed to ultraviolet light can fight osteochondrosis. The scientists further researched and found the active components of anti-chondrosis in human For vitamin D. ^[2]

Vitamin D (VD for short) is a fat-soluble vitamin. It is a group of sterol derivatives with a similar structure that has anti-rickety effect. The main ones are vitamin D3 (cholesterol, cholecalciferol) and vitamin D2 (calciferol). Vitamin D in the diet mainly comes from animal foods such as fish liver, egg yolk, cream, etc. After ingestion, it is absorbed from the small intestine in the presence of bile and transported into the blood in the form of chylomicrons, under the action of liver, kidney, and mitochondrial hydroxylase. Transformed into 1,25-dihydroxyvitamin D3, which is biologically active, can stimulate intestinal mucosal calcium binding protein (CaBP) synthesis, promote calcium absorption, and promote bone calcification. 7-dehydrocholesterol, a cholesterol derivative in the human body, is stored under the skin and can be converted to cholecalciferol under sunlight or ultraviolet radiation. It is an endogenous vitamin D and can promote the absorption of calcium and phosphorus. ^[3]

VD is a derivative of steroids. It is white crystal, soluble in fat, stable in nature, high temperature resistance, oxidation resistance, acid and alkali resistance, fatty acid can destroy it. Animal liver, cod liver oil, and egg yolk are abundant ^[4] . Daily demand for infants, children, adolescents, pregnant women, and nursing mothers is 400 IU (International Units) ^[5] . Adults are susceptible to osteomalacia in the absence of rickets in children. If blood calcium decreases, hand-foot convulsions, convulsions, etc. will also occur, which is also related to tooth development. Too much vitamin D intake can cause high blood calcium, loss of appetite, vomiting, diarrhea and even heterotopic ossification of soft tissues. ^[3]

VD Vitamin D VD Nomenclature and Structure

VD Vitamin D VD Nomenclature

Vitamin D is a nutrient necessary to maintain the life of higher animals. It is a family of molecules with the same A, B, C, and D ring structures but different side chains. The structure of the A, B, C, and D rings is derived from cyclic cyclopentane. Alfene ring structure. Vitamin D has various forms such as D2, D3, D4, D5, D6, and D7 according to the different side chain structures. Only D2 (ergocalciferol) and D3 (cholecalciferol) really play a role in animal nutrition. Active form. ^[6]

Vitamin D2 is a plant-derived ergocalciferol, which is named 9,10-chain-broken- (5Z, 7E) -5,7,10 (10), 22-ergosteretene-3-ol, which is a colorless crystal. , Melting point is 115 ~ 118 , insoluble in water, easily soluble in ethanol and other organic solvents; vitamin D3 is a cholecalciferol present in animal body tissues and cod liver oil, officially named 9,10-chain-broken (5Z, 7E ) -5,7,10 (19), 22-cholestriene-3-ol ergocalciferol, the precursor of which is ergot sterol derived from plants, is a colorless crystal with a melting point of 84 ~ 85 ° C and is insoluble water. ^[6]

VD Vitamin D VD Structure and Chemical Properties

Vitamin D is a fat-soluble vitamin and is a sterol derivative. There are many known vitamin D, the more important is vitamin D

2 and D3, their structures are very similar, but the side chains are different. The structural formula is as shown on the right:

Vitamin D is a colorless crystal. It is soluble in fats, fatty solvents, and organic solvents. It is chemically stable, heat-resistant in neutral and alkaline solutions, and is not easily oxidized, but gradually decomposes in acidic solutions. Vitamin D aqueous solution is unstable due to dissolved oxygen, and its biological effect is significantly reduced after double bond reduction. Therefore, vitamin D should generally be stored in low temperature environment without light, acid, oxygen or nitrogen. ^[2]

VD Vitamin D VD Source

Vitamin D is converted from the corresponding original vitamin D by ultraviolet radiation. Vitamin D is a cyclopentane polyphenanthrene compound. In the original B ring of vitamin D, the 5 and 7 positions are double bonds, which can absorb light quanta with a wavelength of 270 to 300 nm, thereby starting a series of complex photochemical reactions and finally forming vitamin D. If the original vitamin D is ergosterol, the light product is vitamin D2, and if the original vitamin D is 7-dehydrocholesterol, the light product is vitamin D3. Vitamin D2, also known as ergocalciferol, is mainly synthesized in plants, and contains more yeast and ergot. Vitamin D3 is also known as cholecalciferol. The epidermis and skin tissues of most higher animals contain 7-dehydrocholesterol, which can be converted into vitamin D3 by photochemical reaction under sunlight or ultraviolet light. Vitamin D3 is mainly found in marine fish, animal livers, egg yolks and lean meats, skimmed milk, cod liver oil, cheese, nuts and seafood. Both vitamin D have the same physiological effect. Human vitamins are mainly obtained from the body's own synthesis and from animal foods. ^[2]

VD Vitamin D VD Biochemical Metabolism

It has been found that vitamin D itself has no physiological function, and only when it is converted into its active form can it become an effective substance with physiological activity. The active forms of vitamin D are: 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, etc. Among them, 1,25-dihydroxyvitamin D3 is the main form. Vitamin D3 in the diet is absorbed into the blood by emulsification in the small intestine under the action of bile. Vitamin D3 obtained from the diet and the skin is transported to the liver in combination with plasma -globulin, and is first converted into 25-hydroxyvitamin D3 in the endoplasmic reticulum and mitochondria of liver cells through the action of 25-hydroxylase. Then, mixed with the function of oxidase-1 hydroxylase in the kidney, it becomes 1,25-dihydroxyvitamin D3, and its activity is 500-1000 times higher than 25-hydroxyvitamin D3. Then under the load of DBP transporter, it reaches the target organs such as small intestine and bone through blood to bind to nuclear receptors (VDRn) or membrane receptors (VDRm) of the target organs, exerting corresponding biological effects. ^[2]

VD Vitamin D VD main physiological functions

Vitamin D regulates calcium and phosphorus metabolism

The main role of vitamin D is to regulate calcium and phosphorus metabolism, promote calcium and phosphorus absorption in the intestine and bone calcification, and maintain the balance of blood calcium and blood phosphorus. Active vitamin D acts on the nucleus of small intestinal mucosal cells and promotes the biosynthesis of calcinerin. Calcitonin and calcium combine to form a soluble complex, which accelerates the absorption of calcium. Vitamin D promotes the absorption of phosphorus, which may have an indirect effect by promoting the absorption of calcium. Therefore, the total effect of active vitamin D on calcium and phosphorus metabolism is to increase blood calcium and blood phosphorus, so that the levels of plasma calcium and plasma phosphorus reach saturation. It is beneficial for calcium and phosphorus to be deposited on bone tissue in the form of bone salt and promote bone tissue calcification. ^[2]

Vitamin D promotes bone growth

Vitamin D3 can promote bone calcification by increasing calcium and phosphorus absorption in the small intestine. Even if the small intestine absorption does not increase, it can still promote bone salt deposition, which may be the result of vitamin D3 allowing Ca ²⁺ to enter the bone tissue through the osteoblast membrane. VD3 deficiency can lead to calcium absorption and bone mineralization disorders, causing rickets ^[7] . In young children who have been chronically deprived of sunlight, insufficient bone calcification can easily lead to poor bone growth. Simply increasing calcium in food, if vitamin D3 is insufficient, still cannot meet the requirements of bone calcification. However, the effect of 1,25-dihydroxyvitamin D3 on bone tissue is dual. Biological dose of 1,25-dihydroxyvitamin D3 can increase osteoblast activity, increase the number of osteoblasts, and increase the activity of osteoclasts when the physiological dose is exceeded. ^[2]

Vitamin D regulates cell growth and differentiation

1,25-dihydroxyvitamin D3 can regulate the growth and differentiation of leukemia cells, tumor cells and skin cells. For example, fresh cells of patients with myeloid leukemia are treated with 1,25-dihydroxyvitamin D3, the proliferation of leukocytes is inhibited and induced to differentiate. 1,25-dihydroxyvitamin D3 can also differentiate normal human myeloid cells into macrophages and monocytes, which may be a part of its regulation of immune function. 1,25-dihydroxyvitamin D3 also has obvious anti-proliferation and induction differentiation effects on other tumor cells. For example, 1,25-dihydroxyvitamin D3 can reduce the volume of sarcoma cells grown in mice, and significantly inhibit the growth of colon cancer and melanoma plants in mice. It has inhibitory effect on primary breast cancer, lung cancer, colon cancer and bone marrow tumor cells. In addition, 1,25-dihydroxyvitamin D3 can also accelerate the release of tumor necrosis factor by macrophages, which has extensive antitumor effects. 1,25-dihydroxyvitamin D3 can significantly inhibit the proliferation and induce differentiation of epidermal keratinocytes and skin fibroblasts, so it is speculated that 1,25-dihydroxyvitamin D3 may have a therapeutic effect on certain skin hyperproliferative diseases. ^[2]

Vitamin D regulates immune function

Vitamin D has immunomodulatory effects and is a good selective immunomodulator. When the body's immune function is in a suppressed state, 1,25-dihydroxyvitamin D3 mainly enhances the function of monocytes and macrophages, thereby enhancing immune function. When the body's immune function abnormally increases, it inhibits activated T and B Lymphocytes proliferate, thus maintaining immune balance. The mechanisms of 1,25-dihydroxyvitamin D3 to regulate immune function are: mediated by 1,25-dihydroxyvitamin D3 receptor; indirectly stimulate monocyte proliferation and inhibit monocyte proliferation by inhibiting the proliferation of the original monocyte The cells are transformed into phagocytic macrophages. It has certain effects in the prevention and treatment of autoimmune encephalomyelitis, rheumatoid arthritis, multiple sclerosis, type I diabetes and inflammatory bowel disease. ^[2]

VD Vitamin D VD supplement

Normal vitamin D intake

People supplement vitamin D through exposure to sunlight, dietary intake, and vitamin D supplementation. There are not many foods rich in vitamin D. Milk, egg yolks, animal livers (such as cod liver oil) and fatty sea fish (such as salmon) contain a small amount of vitamin D, while plant foods such as cereals, vegetables and fruits contain almost no vitamin D. Vitamin D. Therefore, unlike other nutrients, vitamin D is limited in the diet. In the sunlight, only ultraviolet B with a wavelength of 290 to 315 nm can penetrate the skin, thereby converting 7-dehydrocholesterol in the skin into vitamin D3, but the effect of sunlight exposure is difficult to determine. In winter, sunlight exposure is reduced, and the amount of ultraviolet B that passes through the atmosphere is greatly reduced. In high latitudes, effective sunlight exposure is also greatly reduced. In particular, changes in the lifestyle of modern people, such as the lack of outdoor activities and the use of sunscreen products, will affect the skin's effective synthesis of vitamin D3. Most people need extra vitamin D to achieve the recommended intake. Vitamin D3 (cholesterol) is usually used abroad. As for the recommended dose of vitamin D, it varies from country to country, but has been conservative in the past: in Europe, the recommended dose of vitamin D is only 0 to 400 IU / d; in the United States, the recommended dose for women 51 to 70 years is 400 IU / d It is 600 IU / d for women over 70 years of age; the Canadian Osteoporosis Association recommends that adults consume at least 800 IU / d. ^[8]

Low 1,25-dihydroxyvitamin D3 levels reduce intestinal calcium absorption, leading to secondary hyperparathyroidism, while secondary hyperparathyroidism activates osteoclasts leading to reduced bone mass and bone mass Looseness and increased risk of fractures. Many studies have shown that calcium supplementation and at least 800 IU of vitamin D can reduce the risk of fractures in elderly people over 65 years of age, and that even with small changes in bone density, the risk of fractures has decreased by 1/3. related. ^[8]

Some scholars believe that vitamin D is necessary to prevent osteoporosis. When the serum 1,25-dihydroxyvitamin D3 level is 30ng / mL, it reflects that vitamin D has a good intake or synthesis and can reduce the risk of fracture. However, to obtain this vitamin D level, many people must consume more than daily 1000IU of Vitamin D. For adults over 50 years of age who are at risk of moderate vitamin D deficiency, daily intake of 800-1000 IU vitamin D3 is recommended; for high-risk elderly, 800-2000 IU vitamin D3 is recommended daily. This means that for 1,25-dihydroxyvitamin D3 to reach 20 ng / mL in all individuals, the average serum 1,25-dihydroxyvitamin D3 level must be 30 ng / mL. The recommended daily vitamin D intake should be at least 800 IU, and this recommended amount is not related to light, season, or other multivitamin supplements. For patients with osteoporosis, in addition to calcium and vitamin D, drugs that can effectively prevent fractures must be applied. Calcium and vitamin D have been recognized as the basis for osteoporosis treatment. In 2006, the North American Menopause Society stated that adequate calcium and sufficient vitamin D intake can reduce bone loss in premenopausal and postmenopausal women and reduce the risk of fracture in postmenopausal women with low calcium intake over 60 years of age. The International Osteoporosis Foundation stated in 2008 that patients with osteoporosis should generally be supplemented with at least 1000 mg of calcium and 800 IU of vitamin D daily. ^[8]

In 2011, the Chinese Medical Association also pointed out in the "Guidelines for the Diagnosis and Treatment of Primary Osteoporosis" that calcium and vitamin D are basic supplements for bone health, and it is recommended that adults supplement with 200 IU of vitamin D daily and the elderly daily Supplement 400 to 800 IU, and patients with osteoporosis should also receive medication at the same time. Of course, we also need to pay attention to individual differences in clinical practice, and regularly monitor blood calcium and urine calcium levels. ^[8]

VD Vitamin D VD excess

More common in infants and young children, due to excessive intake of vitamin D. However, the amount of vitamin D tolerated varies from person to person, and allergic children may have symptoms of poisoning if they take 1500 IU (37.5 g) daily. Generally, an adult consumes 100,000 to 150,000 IU (2500-3750 g) daily, and pediatric 2,000 IU / kg (50 g / kg) daily may be poisoned for 2 to 3 months. Injections are more likely to occur than oral. The symptoms of vitamin D poisoning are mainly caused by hypercalcemia, renal damage and soft tissue calcification. Clinical manifestations include loss of appetite, weakness, bradycardia, cardiac arrhythmia, nausea, vomiting, thirst, constipation, polyuria, etc. When long-term vitamin D is too much, hypercalcemia can cause atherosclerosis, extensive soft tissue calcification and different degrees of impaired renal function, and severe cases can be fatal. Too much vitamin D in the mother's body can cause hypercalcemia in infants. If the fetus develops hypercalcemia, the birth weight is low and the heart has murmurs. Severe cases include mental retardation and bone sclerosis. Vitamin D should be discontinued immediately and calcium limited. If necessary, glucocorticoids can be used to reduce blood calcium or intramuscular calcitonin. ^[9]

VD Vitamin D VD deficiency

A disease that affects bone growth due to vitamin D deficiency and bone calcification disorders during growth and development, is rickets. Vitamin D deficiency in infants and young children may be due to too little sunlight exposure, intradermal 7-dehydrocholesterol cannot synthesize vitamin D, or too little food, or premature birth and congenital deficiency, liver and kidney dysfunction, or liver and kidney Gastrointestinal diseases may also be caused by intake of too little calcium or phosphorus, or too much phosphorus. Early loss of appetite, easy crying, sweating, occipital alopecia, later softening of the skull, delayed closing of the anterior palate, long tooth eruption interval, irregular tooth rows, and soft ribs. (Children under 2 years old due to softening of the ribs, chicken chest, chest inset Showing a horizontal groove along the lower edge of the sternum), beaded ribs (hypertrophy of the ribs at the patellar end, which can touch the rounded bulge), bracelets (hypertrophy of the radius ulna at the pedicle, rounded bulge), O-shaped or X-shaped leg, easy Born fractures, low blood calcium. Pregnancy, prolific women, and frail elderly people may have osteomalacia, bone pain, muscle weakness, spine flexion, pelvic deformation, bone tenderness, and spontaneous fractures. It can be seen that serum alkaline phosphatase activity is elevated, and the calcium-phosphorus product is <40. Infants should be encouraged to breastfeed, and children should be properly supplemented with calcium and vitamin D to get more sun exposure. ^[10]

VD Application and production of vitamin D VD

VD Vitamin D VD application

With the deepening of human's research on the physiological activity of vitamin D, the importance of vitamin D has become more prominent, and it is now widely used in three aspects such as pharmaceutical preparations, food additives and feed additives. As a pharmaceutical preparation, it is mainly used in the clinical treatment of rickets, osteoporosis, osteoporosis, hypothyroidism, psoriasis and other diseases; as a food and beverage additive, it can be added to milk, dairy products, beverages, biscuits, In candy, it is used to prevent vitamin D deficiency; as a feed additive for poultry and livestock, vitamin D can increase the output of meat, eggs, and milk, and improve its nutritional value. ^[2]

VD Vitamin D VD Synthesis

We have already known that ergosterol can obtain vitamin D2 by light, and 7-dehydrocholesterol can obtain vitamin D3 by light. In recent decades, many scientists at home and abroad have carried out comprehensive research from the perspective of organic synthetic photochemistry. Ergosterol, the raw material for photochemical synthesis of vitamin D2, is mainly derived from yeast fermentation, and is extracted from waste hyphae or vegetable oil, mushrooms and other products for the production of drugs such as penicillin. ^[2]

Vitamin D3 has a complex structure. Currently, synthetic methods have been reported including a total synthesis method using a small molecule compound as a raw material, a semi-synthesis method using a natural steroid compound as a raw material, and a biosynthesis method. ^[11]

The structure of vitamin D3 and its derivatives mainly includes three parts: side chain, AB ring and D ring. The total synthesis method is to cut the vitamin D3 molecule from the middle triene and the side chain into three synthons, and then through condensation or The coupling method stitches the three parts together. The process of the total synthesis method is relatively complicated and the yield is very low. It is generally used for theoretical studies such as the construction of D3 derivatives with a special structure, which is often difficult to produce. Semi-synthesis is mainly to select appropriate natural steroids as raw materials and then Modification and modification of A, B and side chains. Finally, vitamin D3 was constructed by photochemical ring-opening reaction. This method is easy to operate and is currently oriented to industrialization. Most of the vitamin D3 raw materials on the market are synthesized by chemical methods using cheap and readily available natural steroids as raw materials. Compared with traditional chemical synthesis, The reaction has the advantages of good reaction selectivity, fast reaction rate, and short steps. In recent years (2015), related studies have also reported the application of biological method to vitamin D3, but no industrial production has been carried out. ^[11]