STUDY - Technical - New Dacian's Medicine
Vitamin
Deficiency and Excess (3)
Translation Draft
I'll try to finalize the vitamin deficiency elements. We've reached biotin. This has a role as a cofactor in mammalian carboxylases. The vitamin is ingested mainly in a protein-related form, is hydrolyzed by pancreatic biotinidase and is probably absorbed through an active process. Within cells, biotin binds covalently to apocarboxylases, to form 4 haloenzymes that catalyze the incorporation of bicarbonate into the substrate, acetyl CoA carboxylase, pyruvate carboxylase, methylcrotonil CoA carboxylase, propionyl CoA carboxylase.
Biotin deficiency in humans occurs in at least three circumstances: prolonged consumption of raw white (which binds biotin in the gut and decreases its absorption), in amlabsorption, as a component of protein-calorie malnutrition, after parenteral nutrition without biotin supplements and in people with multiple carboxylase deficiencies due to abnormalities in holocarboxylase-synthesis or biotinidase. In all situations, the manifestations characteristic of biotin deficiency are similar to those of essential fatty acid deficiency and consist of perioral dermatitis, conjunctivitis, alopecia, ataxia and, in children, the delay of mental development. In addition, multiple carboxylase deficiency can cause severe neurological impairment and urinary elimination of organic acids. Diagnosis can be established by highlighting the decrease in urinary excretion of biotin or by demonstrating the resolution of the disease at the administration of 100 mg/ day biotin.
We have reached vitamin A. From a biochemistry point of view, vitamin A (retinol) is brought into the body by food intake or can be synthesized from vegetable carotene. The richest sources of vitamin A are the liver, milk and kidneys, where they are largely in the form of fatty acid esters. They are hydrolyzed during digestion, the vitamin is absorbed in free form, reesterified with fatty acids in the intestinal mucosa and enters circulation through the lymph, in the form of chilomicrons. The carotene substrate for vitamin A synthesis (mainly beta-carotenes) is widespread in the plant kingdom. Beta-carotene is absorbed as such or cleaved into the intestinal tract and forms two retinal molecules.
This is reduced in the presence of aldehyde reductase to retinol. Whatever the source of retinol, it is stored in the liver in esterified form. The normal reserve is 300-900 mg. Before leaving the liver, retinylesters are hydrolyzed and free alcohol is bound to a specific transporter protein, RBP, which provides transport to peripheral tissues. In vitamin A deficiency, the release of RBP from the liver is inhibited, the protein accumulates in the liver (during administration, RBP is rapidly mobilized from existing deposits). Approximately equal amounts of retinol are secreted in the bile and urine.
From the point of view of the mechanism of action, the most well-known role of vitamin A is the visual one (in the retina, vitamin A constitutes the prosthetic grouping of the carotenic proteins that provide the molecular basis of the occurrence of visual excitation). In addition, vitamin A is necessary in growth, reproduction and in maintaining vital functions. Retinol-phosphate-manosis is a glycolipid present in a wide variety of cell membranes, and vitamin A has a leading role in the synthesis of glycoproteins.
The importance of glycoproteins for the functioning of any cell emphasizes that vitamin A is essential. In the exercise of its functions, it appears to bind to a protein that regulates transcription and controls gene expression. The yield of the transformation of beta-carotene into vitamin A in the human body is 1 to 6 (0,167). Other carotenoids with provitamin action A typically have half the activity of beta-carotene. Pregnancy, conditions that disrupt absorption or storage, excessive use or increased excretion lead to increased vitamin A requirements.
In the case of experimental depletion, administration of a diet deficient in retinol and carotene leads to a decrease in plasma levels and a halving of the body's reserves. Deficiency is manifested by follicular hyperkeratosis, impaired adaptation to darkness and abnormalities of the electroretinogram. They disappear after supplementation with 150 mg retinol or 300 mg of beta-carotene daily. In terms of clinical deficiency, endemic deficiency occurs by inadequate intake of vitamin or provitamins A and occurs concurrently with other nutritional deficiencies or as a complication occurring in the carrier of diseases.
In developing countries, vitamin A deficiency is a major cause of blindness in young people, aleading result of a lack of consumption of green fruit vegetables or other sources of vitamin A. These children are particularly sensitive to measles complications. Vitamin A deficiency may contribute to protein-calorie malnutrition. In developed countries, vitamin A deficiency occurs either through intestinal malabsorption (in sprue or intestinal bypass) or by abnormal storage (hepatic disease) or through increased vitamin (proteinuria) destruction or excretion.
Patients undergoing total parenteral nutrition may experience vitamin A deficiency as a result of its destruction in infused fluids due to prolonged storage. The most early symptom is nocturnal blindness, followed by retinal degeneration. The bulbar conjunctiva dries (xerosis) and small, gray plates with a foamy surface (Bitot spots) appear. These early lesions are reversible under treatment. More severe effects of deficiency are ulcerations and necrosis of the cornea (keratomalacia), which leads to perforations, endophthalmia and blindness. There may be dryness and hyperleratosis in the skin. The plasma level of vitamin A does not accurately reflect existing deposits.
Measuring adaptation to darkness, performing scogotry and electroretinography are useful indicators, but require trained personnel and expensive equipment (therefore, the diagnosis is usually based on suspicion of deficiency in malnourished children or patients who have a predisposition for the development of hypovitaminosis A). Nocturnal blindness and conjunctival impairment respond favorably to 300,000 IU/ day of vitamin A for one week. Corneal damage is a therapeutic emergency, usually taking 20,000 IU/ kg body daily for 5 days. Children at risk of hypovitaminosis A who become ill with measles will receive 200,000 IU per bone daily for 2 days.
It's the turn of vitamin E. From a biochemistry point of view, eight tocopherols have vitamin activity E. The alpha tocopherol structure, the most active and most widespread of tocopherols. Vitamin E is absorbed from the gastrointestinal tract by a mechanism similar to the absorption of other fat-soluble vitamins, reaches through the lymph into the bloodstream, being bound first by chilomicrons and then by plasma beta-lipoproteins. Plasma levels correlate with plasma lipid levels. The vitamin is stored in all tissues, with tissue deposits providing protection against deficiency for a long time. Approximately three-quarters of the vitamin is excreted bile, and the rest is urinaryly eliminated in the form of glucuronides.
Metabolites with quininic structure (including similar to ubichinone) are present at the tissue level. Vitamin E acts as an antioxidant rather than a specific cofactor. It probably inhibits the oxidation of essential cellular constituents and prevents the formation of toxic products resulting from oxidation. Other antioxidants, such as selenium, sulfur amino acids, ubichinone group, can lead to the disappearance of symptoms of vitamin e deficiency. Diets have high content of polyunsaturated fatty acids increase the need, while antioxidant-rich diets decrease the requirement of vitamin E.
This is widespread in food, so primary deficiency has not been identified in children or adults who did not have other conditions. Newborns have a plasma concentration of about 1/5 di maternal level, demonstrating that transplacental transfer is low (human milk, unlike cow milk, contains enough vitamin E to provide the need for an infant).
Long-term studies have shown that the plasma nival of vitamin E decreased significantly only months after the establishment of the deficient diet. No manifestations of deletation were observed in healthy volunteers, making it difficult to establish that tocopherol is a human vitamin. In terms of clinical deficiency, the decrease in vitamin E in the body is associated with discrete symptoms, such as when the deficiency is due to a selective malabsorption of the vitamin or when it is a recessive autosomal mutation causes vitamin E deficiency and ataxia.
More commonly, lipid malabsorption can lead to a decrease in the level of all fat-soluble vitamins, including vitamin E (children with abetalipoproteinemia or chronic cholestatic liver disease appear to have increased susceptibility). For the determination of vitamin E ration, it is preferred to calculate the ratio of serum vitamin E to total serum lipids. Deficiency produces manifestations such as areflexia, decreased proprioceptive and vibrating sensitivity, impaired gait, impaired visual focus (these are associated with degeneration of the posterior columns of the spinal cord, selective loss of high-calibre axons, myelinized, from peripheral nerves and the appearance of spheroids in the gracil and curate cells in the brain).
Treatment (50-100 IU/ day, per bone) is much more effective if established during the early stages of the disease.
There is still "discussed" about vitamin K. Vitamin K is made up of a chinonic ring to which a radical is attached in the lateral position (this varies depending on the origin of the vitamin). Vitamin K1 (philochinone) is found in most vegetables, especially those with green fruits, and vitamin K2 is produced by the intestinal bacterial flora, but not in sufficient quantity to ensure daily needs. Vitamin K activity is structurally linked to a simple compound, 2-methyl-1,4-naftochinone (menadione).
Menadionis is formed in the intestine by bacterial splitting of the lateral lysed chain. After absorption, menadione is converted in the body into menachinone, the active compound. The vitamin is part of the composition of a specialized microsomeenzyme system, which achieves posttranslational teta-carboxylation of glutamic acid, with the production of proteins from plasma, bone, kidneys and urine, including the precursor proteins of coagulation factors II, VII, IX and X and the inhibitory proteins of coagulation, C and S. Death by hemorrhages (in case of deficiency) occurs before the deficiency of other carboxylproteins becomes manifest.
Warfarin anticoagulant drugs produced hypoprothrombinemia by inhibition of teta-carboxylation of precursor proteins. Typically, 80% of vitamin K is absorbed into the lymph of the small intestine. Deficiency may occur in combination with conditions that affect fluid absorption. In addition, oral treatment with long-term antibiotics can temporarily suppress the intestinal flora and by decreasing the production of vitamin K can generate deficiency in the absence of dietary supplementation. Newborns have a tendency to hypovitaminosis K and have low plasma levels of several coagulation factors in the protrombic complex.
Such deficiencies occur due to the minimum reserves of vitamin K present at birth, lack of intestinal flora and limited intake, but it is not clear whether all newborns should receive vitamin K (routine). Routine determination of prothrombin should be performed before any surgery or antepartum. People with levels below 70% will receive vitamin K treatment. Vitamin K deficiency can be separated from hypoprothrombinemia in liver disease by highlighting the plasma accumulation of non-carboxylate protrombic precursors.
Ready for today. Next time we talk about excess vitamins...
I'll try to finalize the vitamin deficiency elements. We've reached biotin. This has a role as a cofactor in mammalian carboxylases. The vitamin is ingested mainly in a protein-related form, is hydrolyzed by pancreatic biotinidase and is probably absorbed through an active process. Within cells, biotin binds covalently to apocarboxylases, to form 4 haloenzymes that catalyze the incorporation of bicarbonate into the substrate, acetyl CoA carboxylase, pyruvate carboxylase, methylcrotonil CoA carboxylase, propionyl CoA carboxylase.
Biotin deficiency in humans occurs in at least three circumstances: prolonged consumption of raw white (which binds biotin in the gut and decreases its absorption), in amlabsorption, as a component of protein-calorie malnutrition, after parenteral nutrition without biotin supplements and in people with multiple carboxylase deficiencies due to abnormalities in holocarboxylase-synthesis or biotinidase. In all situations, the manifestations characteristic of biotin deficiency are similar to those of essential fatty acid deficiency and consist of perioral dermatitis, conjunctivitis, alopecia, ataxia and, in children, the delay of mental development. In addition, multiple carboxylase deficiency can cause severe neurological impairment and urinary elimination of organic acids. Diagnosis can be established by highlighting the decrease in urinary excretion of biotin or by demonstrating the resolution of the disease at the administration of 100 mg/ day biotin.
We have reached vitamin A. From a biochemistry point of view, vitamin A (retinol) is brought into the body by food intake or can be synthesized from vegetable carotene. The richest sources of vitamin A are the liver, milk and kidneys, where they are largely in the form of fatty acid esters. They are hydrolyzed during digestion, the vitamin is absorbed in free form, reesterified with fatty acids in the intestinal mucosa and enters circulation through the lymph, in the form of chilomicrons. The carotene substrate for vitamin A synthesis (mainly beta-carotenes) is widespread in the plant kingdom. Beta-carotene is absorbed as such or cleaved into the intestinal tract and forms two retinal molecules.
This is reduced in the presence of aldehyde reductase to retinol. Whatever the source of retinol, it is stored in the liver in esterified form. The normal reserve is 300-900 mg. Before leaving the liver, retinylesters are hydrolyzed and free alcohol is bound to a specific transporter protein, RBP, which provides transport to peripheral tissues. In vitamin A deficiency, the release of RBP from the liver is inhibited, the protein accumulates in the liver (during administration, RBP is rapidly mobilized from existing deposits). Approximately equal amounts of retinol are secreted in the bile and urine.
From the point of view of the mechanism of action, the most well-known role of vitamin A is the visual one (in the retina, vitamin A constitutes the prosthetic grouping of the carotenic proteins that provide the molecular basis of the occurrence of visual excitation). In addition, vitamin A is necessary in growth, reproduction and in maintaining vital functions. Retinol-phosphate-manosis is a glycolipid present in a wide variety of cell membranes, and vitamin A has a leading role in the synthesis of glycoproteins.
The importance of glycoproteins for the functioning of any cell emphasizes that vitamin A is essential. In the exercise of its functions, it appears to bind to a protein that regulates transcription and controls gene expression. The yield of the transformation of beta-carotene into vitamin A in the human body is 1 to 6 (0,167). Other carotenoids with provitamin action A typically have half the activity of beta-carotene. Pregnancy, conditions that disrupt absorption or storage, excessive use or increased excretion lead to increased vitamin A requirements.
In the case of experimental depletion, administration of a diet deficient in retinol and carotene leads to a decrease in plasma levels and a halving of the body's reserves. Deficiency is manifested by follicular hyperkeratosis, impaired adaptation to darkness and abnormalities of the electroretinogram. They disappear after supplementation with 150 mg retinol or 300 mg of beta-carotene daily. In terms of clinical deficiency, endemic deficiency occurs by inadequate intake of vitamin or provitamins A and occurs concurrently with other nutritional deficiencies or as a complication occurring in the carrier of diseases.
In developing countries, vitamin A deficiency is a major cause of blindness in young people, aleading result of a lack of consumption of green fruit vegetables or other sources of vitamin A. These children are particularly sensitive to measles complications. Vitamin A deficiency may contribute to protein-calorie malnutrition. In developed countries, vitamin A deficiency occurs either through intestinal malabsorption (in sprue or intestinal bypass) or by abnormal storage (hepatic disease) or through increased vitamin (proteinuria) destruction or excretion.
Patients undergoing total parenteral nutrition may experience vitamin A deficiency as a result of its destruction in infused fluids due to prolonged storage. The most early symptom is nocturnal blindness, followed by retinal degeneration. The bulbar conjunctiva dries (xerosis) and small, gray plates with a foamy surface (Bitot spots) appear. These early lesions are reversible under treatment. More severe effects of deficiency are ulcerations and necrosis of the cornea (keratomalacia), which leads to perforations, endophthalmia and blindness. There may be dryness and hyperleratosis in the skin. The plasma level of vitamin A does not accurately reflect existing deposits.
Measuring adaptation to darkness, performing scogotry and electroretinography are useful indicators, but require trained personnel and expensive equipment (therefore, the diagnosis is usually based on suspicion of deficiency in malnourished children or patients who have a predisposition for the development of hypovitaminosis A). Nocturnal blindness and conjunctival impairment respond favorably to 300,000 IU/ day of vitamin A for one week. Corneal damage is a therapeutic emergency, usually taking 20,000 IU/ kg body daily for 5 days. Children at risk of hypovitaminosis A who become ill with measles will receive 200,000 IU per bone daily for 2 days.
It's the turn of vitamin E. From a biochemistry point of view, eight tocopherols have vitamin activity E. The alpha tocopherol structure, the most active and most widespread of tocopherols. Vitamin E is absorbed from the gastrointestinal tract by a mechanism similar to the absorption of other fat-soluble vitamins, reaches through the lymph into the bloodstream, being bound first by chilomicrons and then by plasma beta-lipoproteins. Plasma levels correlate with plasma lipid levels. The vitamin is stored in all tissues, with tissue deposits providing protection against deficiency for a long time. Approximately three-quarters of the vitamin is excreted bile, and the rest is urinaryly eliminated in the form of glucuronides.
Metabolites with quininic structure (including similar to ubichinone) are present at the tissue level. Vitamin E acts as an antioxidant rather than a specific cofactor. It probably inhibits the oxidation of essential cellular constituents and prevents the formation of toxic products resulting from oxidation. Other antioxidants, such as selenium, sulfur amino acids, ubichinone group, can lead to the disappearance of symptoms of vitamin e deficiency. Diets have high content of polyunsaturated fatty acids increase the need, while antioxidant-rich diets decrease the requirement of vitamin E.
This is widespread in food, so primary deficiency has not been identified in children or adults who did not have other conditions. Newborns have a plasma concentration of about 1/5 di maternal level, demonstrating that transplacental transfer is low (human milk, unlike cow milk, contains enough vitamin E to provide the need for an infant).
Long-term studies have shown that the plasma nival of vitamin E decreased significantly only months after the establishment of the deficient diet. No manifestations of deletation were observed in healthy volunteers, making it difficult to establish that tocopherol is a human vitamin. In terms of clinical deficiency, the decrease in vitamin E in the body is associated with discrete symptoms, such as when the deficiency is due to a selective malabsorption of the vitamin or when it is a recessive autosomal mutation causes vitamin E deficiency and ataxia.
More commonly, lipid malabsorption can lead to a decrease in the level of all fat-soluble vitamins, including vitamin E (children with abetalipoproteinemia or chronic cholestatic liver disease appear to have increased susceptibility). For the determination of vitamin E ration, it is preferred to calculate the ratio of serum vitamin E to total serum lipids. Deficiency produces manifestations such as areflexia, decreased proprioceptive and vibrating sensitivity, impaired gait, impaired visual focus (these are associated with degeneration of the posterior columns of the spinal cord, selective loss of high-calibre axons, myelinized, from peripheral nerves and the appearance of spheroids in the gracil and curate cells in the brain).
Treatment (50-100 IU/ day, per bone) is much more effective if established during the early stages of the disease.
There is still "discussed" about vitamin K. Vitamin K is made up of a chinonic ring to which a radical is attached in the lateral position (this varies depending on the origin of the vitamin). Vitamin K1 (philochinone) is found in most vegetables, especially those with green fruits, and vitamin K2 is produced by the intestinal bacterial flora, but not in sufficient quantity to ensure daily needs. Vitamin K activity is structurally linked to a simple compound, 2-methyl-1,4-naftochinone (menadione).
Menadionis is formed in the intestine by bacterial splitting of the lateral lysed chain. After absorption, menadione is converted in the body into menachinone, the active compound. The vitamin is part of the composition of a specialized microsomeenzyme system, which achieves posttranslational teta-carboxylation of glutamic acid, with the production of proteins from plasma, bone, kidneys and urine, including the precursor proteins of coagulation factors II, VII, IX and X and the inhibitory proteins of coagulation, C and S. Death by hemorrhages (in case of deficiency) occurs before the deficiency of other carboxylproteins becomes manifest.
Warfarin anticoagulant drugs produced hypoprothrombinemia by inhibition of teta-carboxylation of precursor proteins. Typically, 80% of vitamin K is absorbed into the lymph of the small intestine. Deficiency may occur in combination with conditions that affect fluid absorption. In addition, oral treatment with long-term antibiotics can temporarily suppress the intestinal flora and by decreasing the production of vitamin K can generate deficiency in the absence of dietary supplementation. Newborns have a tendency to hypovitaminosis K and have low plasma levels of several coagulation factors in the protrombic complex.
Such deficiencies occur due to the minimum reserves of vitamin K present at birth, lack of intestinal flora and limited intake, but it is not clear whether all newborns should receive vitamin K (routine). Routine determination of prothrombin should be performed before any surgery or antepartum. People with levels below 70% will receive vitamin K treatment. Vitamin K deficiency can be separated from hypoprothrombinemia in liver disease by highlighting the plasma accumulation of non-carboxylate protrombic precursors.
Ready for today. Next time we talk about excess vitamins...
Understanding, Love and
Gratitude!!!
Dorin, Merticaru