CHIMERIC PROTEINS

Chimeric protein

The chimeric proteins are also called fusion proteins. These are products of chimeric genes. Chimeric proteins are produced naturally as well by gene recombination methods.

 

Natural chimeric proteins

 The chimeric protein produced naturally is the result of cancer such as the bcr abl fusion gene that produces chimeric protein. It causes chronic myelogenous leukemia.

 Other chimeric proteins that are the result of natural processes are formed due to composite mutations such as

 Gene translocations are when a segment of the gene is translocated to another part of the genome. The newly modified gene now produces chimeric protein.

 Duplication is another method of mutation that results in duplication of a segment of a gene in its position that also results in the formation of the chimeric protein.

 Retrotransposons are viral genes that have been incorporated into the genome in evolution. These are produced by reverse transcription and they can translocate themselves to other positions in the genome. This will result in mutation of the gene and protein if produced will be chimeric protein. 

 A chimeric protein structurally has two or three domains that are its functional part. This function part is produced from different genes of different species they will result in the formation of chimeric genes in cells these must be linked with a linker protein. 

The linker protein can be flexible if it consists of poly glycine and rigid if it consists of Proline amino acids. A chimeric protein can be functional or non-functional. The proteins are produced when the functional domains are kept intact but the regulatory part of the gene is transformed from another gene in this way the function of the protein can be upregulated or downregulated regulated.

Chimeric Gene construction

 Non-functional chimeric proteins are usually produced when the two domains of a protein are taken from different species. In this case, they may do not fold in the proper confirmation so this protein will lose its function.

TYPES OF CHIMERIC PROTEINS

 Based on fusion chimeric protein can be N- terminal fusion protein or C-terminal fusion protein. The N- terminal fusion protein has the novel protein attached to the N- terminal of a protein. The C-terminal fusion protein has the novel protein attached to the C- terminal of the protein.

Fusion proteins

 Why do we need to produce chimeric protein

Chimeric proteins are produced for hormones, antibodies, Secretory proteins, enzymes, or structural components of the cells. 

 Chimeric proteins are produced to increase secretion of the proteins, for example in case of antibodies 

Chimeric proteins are produced to increase the solubility of the protein.

 Chimeric proteins are produced to increase the stability of the protein.

 Functional proteins are produced to upregulate or downregulate the function of the protein.

CHIMERIC PROTEINS OF EUKARYOTES

 If chimeric proteins are produced for eukaryotes they must be having some specific components of Eukaryotic gene expression such as Eukaryotic gene has a special structure it has a promoter, inducer, and structural gene.

 The structural genes are separated from each other by introns, that are removed to produce mature mRNA.If the recombinant chimeric gene does not have this capability, it will not function in the Eukaryotic system,

Further in eukaryotes transcription occur in the nucleus so the gene must be located in the nucleus i.e. it must be integrated with the genome in such a way that it can be transcribed. 

It must have the regulatory part that will help its expression in the Eukaryotic system.

 Further, after transcription mRNA is to be translocated outside the nucleus in eukaryotes. So mRNA must-have cap and tail, this helps the nuclear pore complex to recognize mRNA and transfer it to the cytoplasm. 

 The mature mRNA must be capable of being recognized by the ribosome. it must have a specific leader sequence and it must have the initiator codon.

 Further, there must be Codon Optimisation must be done as some codon in bacteria are more common than the other, such as lysin is coded by AAA only 25% and by AAG 75%. translation will be less efficient mRNA has AAA codon more frequent than AAG codon.

 Steps involved in the production of chimeric protein include

 Gene is selected for which a chimeric protein is to be produced for this BLAST studies are done for a protein and compatibility of proteins are established so that the related genes are selected. 

These genes are then used to generate cDNA library .

 From the cDNA library a chimeric gene is produced.  

 This chimeric gene is used for the production of chimeric protein this chimeric protein is produced by inserting the chimeric gene in some Eukaryotic expression vector.

EUKARYOTIC EXPRESSION VECTOR CHIMERIC PROTEIN PRODUCTION

Expression Vector(Ampr -ampicillin resistance gene,ori- origin of replication,G.I. gene of interest,Lac1- lactose metamolism gene)

 In the expression vector, a chimeric gene must have a promoter and inducer which can be CM4, the Pro Asp tag and his tag, and the thyroxine gene for the thyroxine(G.I.) hormone production.

 The promoter can be a constitutional or specific promotor when it is expressed in specific cells constitutional when the protein is expressed in all body cells.

Gene construct for eukaryotic expression

 CM4 is a general inducer

 Pro Asp tag is for cleavage.

 His tag is for purification and thyroxine is for thyroxine protein production. 

 Chimeric protein genes are digested with arl restriction enzyme this enzyme results in the formation of the complementary site in the gene. The complementary site is joined by a linker gene after joining the two genes they are inserted into the expression vector as Baculovirus expression vector.

 This vector is used to insert the chimeric gene in insects so chimeric protein is expressed in insects. Baculovirus expression vector has left border and right border sequences, a terminating sequence, a promoter, and a gene of interest which is inserted at the site of polyhedrin gene.

 This baculovirus vector is then inserted into insect for the expression of chimeric protein.

Baculovirus expression vector( L- left border,R- right border, P- promotor, T- terminator, GoI- gene of interest)

 The expression vector produced from Bculovirus vector is Bacmid vector . It has an antibiotic-resistant chain bacterial gene for expression multiple cloning sites. These vectors are used for bacterial expression as well insect expression.

Precautions taken in chimeric proteins production

Select proper expression vector.

Select proper expression system i.e. E.coli, yeast, insect or mammalian cells.

mRNA should be tagged for its targeting to specific organelle ; mitocondria, ER, golgi, cell membrane.

WHY DO I GET BOILS?

 

 BOILS are infected hair follicles. It can be observed in any part of the body, even on your scalp.  These are caused by bacterial infections in hair follicles.

 They are the result of bacterial infection and inflammation. They can appear on any part of the body and especially in the parts which are more prone to bacterial infection such as the buttocks, thighs, neck, roots of eyelashes, and face

 In the area of infection, we may feel inflammation due to which the area becomes pink or red. It may appear similar to a pimple. But if the infection continues or becomes worse. The boil area gets in plum and hard. This area becomes filled with pus and this pus causes pressure due to which pain is felt.

 This is a simple immune reaction against the infection. But this causes pain and a feeling of burning. The reaction is worse in immunocompromised people, people with diabetes or eczema. In the worst situation may cause fever and chills.

 Bacteria that cause boils or furuncles are Staphylococcus aureus. So boils are also called Staph infection This bacterium is a normal resident of our skin. Infection occurs when we have dry skin, breaks in skin or rashes, or any scratch wound. This helps the bacteria to enter the skin and reach the root of the hair follicle. Extremely dry itchy skin increases the staph infection.

 A person may get the infection from a fellow person who has already the staph infection. He may get the infection if he uses articles of the infected person. The boils treat themselves within a set frame of the period.

The development of furuncles or boils

Bacteria present on the skin enter into the subcutaneous region.

It multiplies there.

Macrophages identify these bacteria.

Cytokines are secreted by macrophages.

These cytokines start inflammation reactions.

Lymphocytes are recruited.

Adipose tissue multiplies.

Neutrophils cleanse the bacteria.

A. Start of infection

B.Adipogenesis

C. Cleansing the bacteria

TREATMENTS AND PREVENTION OF BOILS OR FURUNCLES

 Physical drainage of pus or using processes that facilitate fast drainage is the most important treatment in boils. Applying warm pads, using painkillers to relieve the pain, is also helpful in boil treatment as it helps in boil drainage. The use of antibacterial soap on the area of infection is advised to stop staph infection in nearby areas.

 Only in case of severe infection, you may need antibiotics with the advice of your doctor. If the condition worsens with time you may get repeated infection of the bacteria.

People may develop sepsis which is the worst condition where infection spread to their bloodstream and severe immunological reaction result in cytokines storm that may result in organ dysfunction, this condition is called bacterial sepsis.

Antibiotic-resistant bacteria may develop MRSA. This is the infection of Methicillin-Resistant Staphylococcus aureus. These infections are difficult to treat.

The most important treatment for the person who gets frequent boils is

 to keep your skin clean,

 bath regularly,

 use antibacterial soap,

 keep your articles separate from other persons such as bed-sheet, towel t-shirts, and clothing. Wash your clothes and dry them on Sun.

 Keep your skin clean and prevent over-drying of the skin use body oils or body lotions so that skin may not become over dry or itchy.

  Avoid contact with infected people.

Once the pus has been drained, don’t let the wound open.

Keep the area clean.

Don’t let the situation worsen which may lead to bacterial sepsis.

See your doctor before the worse situation arise.

 

CYTOKINES

What are cytokines? What is their role in immune response? What is a cytokine storm that is believed to cause death in Corona? We will try to find out answers to all these questions in this article, further, we will focus on the IL-17 signal transduction pathway.

Cytokines are glycoproteins that are involved in cell-to-cell communication. Cytokines are secreted by various blood cells. These are low molecular weight, proteins that are involved in the immune response.

 Properties of cytokines based on action

 Cytokines can be autocrine, paracrine, or endocrine. Autocrine cytokines are secreted by the cell on which they act upon. Paracrine cytokines act on neighboring cells. Endocrine cytokines act on distant cells. These are transported through the circulatory system

.

 Cytokines show Redundancy, Synergy, Antagonism, Cascade induction 

Classification of cytokines

 Most of the cytokines have been named based on the cell that produces them for example lymphokines are the cytokines secreted by lymphocytes, monokines are the cytokines secreted by monocytes or macrophages.

Classification of cytokines

Broadly cytokines are divided into 5 different classes based on the receptor they use and their broad function.

Interleukins are the cytokines that are secreted by one lymphocyte and affect other lymphocytes

Interferons are the cytokines that are secreted In response to some viral infections the effect on the infected cells.

Tumor necrosis factor effect on the cancer cells. They kill the cancerous cells.

Chemokines are the cytokines that show chemotaxis. They invite cells and molecules to the site of inflammation.

G-CSF, GM-CSF, M-CSF are growth factors secreted by granulocytes, granulocyte macrophages, or macrophages, thus their name is granulocyte colony-stimulating factors, granulocyte-macrophage colony-stimulating factors, and macrophage colony-stimulating factors respectively. These are involved in cell recruitment and proliferation i.e. T-cell, B-cell proliferation.

 Cytokine can be part of innate immunity or adaptive immunity

 Cytokines of innate immunity

These include interleukin 1, tumor necrosis factor-alpha, interleukin 12(IL-12), interleukins 6(IL-6), interferon-alpha(INF-a), interferon-beta(INF-b), These cytokines are secreted by monocytes, macrophages, dendritic cells or epithelial cells, or fibroblast cells.

 Cytokines of adaptive immunity 

These include cytokines that are secreted by T cells i.e. T helper cells or T helper 2 cells. These include interleukin-2, interleukin-4, interleukin 5 interleukins 25, TNFβ, interferon-gamma these are involved in the T cell effector system of adaptive immunity, which is the activated T helper cell and  T cytotoxic cell or they are involved in the production of antibodies by B cells.

 Cytokines receptors

 These are surface molecules of effector cell receptors that fall in 5 different families.

GM-CSF receptor family act upon hematopoietic stem cells and progenitor cells and activates monocytes Induce megakaryocytes differentiation all these cytokines induce eosinophil proliferation, basophil degranulation, and release of histamine. GM CSF receptor subfamily which has a beta subunit common.  

 Immunoglobin superfamily receptors interact in antibodies have a single large protein that has multiple domains.

 

Class 1 cytokines receptor family is also known as hematopoietic in receptor family. Class 1 cytokines receptors have conserved four cysteine Residue and conserved tryptophan Serine- any amino acid- tryptophan- serine domain (WSXWS).

 Class -2 cytokines receptors have four cysteine Residue which is conserved but lacks WSXWS cytokine. Class-2 cytokines receptor family known as interferon receptor family, tumor necrosis factor receptor family

IL-2 receptor subfamily that has a common Gamma subunit. Other subunits of these receptors are made of different alpha and beta subunits.

 IL- 6R Subfamily  has gp-130 protein common which indicates they  have common signaling pathway these cytokines stimulates megakaryocyte maturation and platelet production

 Chemokines receptor family receptors are different from other families. They are small in size and have single that span across the membrane. At the cytoplasmic end, these are associated with G-protein.

 IL-2 signal transduction subfamily is consists of a heterotrimer that consists of Alpha, Beta, and Gamma subunits, of this Gamma subunit, is common for all the other interleukins receptors that are identical to IL-15, IL-7, IL-9, IL-4. Gamma subunit is signal transduction subunit. x-linked severe combined immunodeficiency XSCID occurs due to loss of function of the cytokine receptor of the IL-2 subfamily. The signaling pathway involves protein phosphorylation their dimerization and activation.

 Receptors IL-2 receptors are involved in Tcell proliferation alpha and gamma subunit consists of conserved for cysteine Residue, alpha subunit however is different in IL-2 receptors. The alpha subunit is only expressed by the activated T cells. When all three subunits alpha, beta, gamma are present they form high-affinity receptors.

 Alpha- gamma subunits are constitutively expressed. Alpha and Beta chains are more restricted Tcell and enhanced after antigen has activated the Tcell lymphocytes this ensures that only antigen-activated CD4 + or CD8 + cells will Express high-affinity interleukin-2 receptor.

IL-2 signal transduction pathway involved binding of the cytokine to gamma subunit, Alpha- Beta subunit of the cytokines receptor form dimer, this dimerization of cytokines receptor that leads to activation of Janus kinase.

 The tyrosine kinase enzymes activated JAK create a docking site for STAT(Signal Transducers and Activators of Transcription) which is a transcription factor its phosphorylation occurs at a specific tyrosine residue. The phosphorylated STAT proteins now form a dimer.

 It now acts as an activated transcription factor that is translocated to Nucleus where it binds to a specific gene to enhance its transcription. STAT is a signal transducer and activator of transcription

IL-2 signal transduction pathway.

IL-17 signal transduction pathway

IL-17 signal transduction pathway involved IL 17 receptor. This receptor is a heterotrimer. Which has a IL- 17 RA, a IL- 17RA,17RC. This receptor when binding with IL-17 interleukin activates and enzyme Act 1 which is a dimer associated with heat shock protein 90(Hsp90)  this enzyme activate TRAF6 protein. This protein is involved in three different Pathways in which it activates C/EBP beta and MAP kinase(involved in cell division) and NF Kappa dimer.MAP kinase through another protein AP-1 is involves the activation of several genes present in the nucleus. These genes are required for cell division, proliferation, or differentiation. These three different Pathways have three different effects they may synthesize some new cytokines that are involved in inflammatory (IL-6, IL-4, TNFalpha ) response. They may synthesize tumor necrosis factors that are involved in Cancer response or they may synthesize chemokines further they may recruit Th2 helper cells for adaptive immunity response.

IL-17 SIGNAL TRANSDUCTION PATHWAY

CYTOKINE STORM AND COVID RELATED DEATHS

Cytokines Storm is also referred to as hypercytokinemia. Cytokine Storm has been seen in various infectious diseases and most recently in the case of severe Covid19 infections. In general cytokine storms result in acute inflammation which has 5 different symptoms such as redness, swelling, heat, pain, and loss of function. Redness is due to inflammation which is a host reaction against some infection. 

This inflammation allows the plasma protein and leukocyte to reach the site of infection. This is a normal reaction, however, during cytokines Storm, various inflammatory cytokines are produced in excess they may result in organ failure or multiple organ failure and may ultimately result in the death of the patient.

 Inflammatory cytokines are IL-6, IL-4, IL-2, TNF- a, and chemokines CXCL10, CCL2. The excessive secretion of the cytokines has been observed in infectious diseases as well as in the case of SARS Cov-2, MERS Cov-2. The excessive secretion of the cytokine is a warning sign in case of Covid-19 infection they may result in immunopathogenic damage, that not only result in an ARDS(Acute Respiratory Distress Syndrome)  where lungs fail to supply oxygen to different organs that may cause excessive tissue damage, organ failure, and death( reference news medical life science).

THE 5 to 7 days is critical for cytokines storm in case of covid 80% of the patient tends to improve after this time only 20% patient may show severe pneumonia and approximately 2% will ultimately succumb this virus. The use of a range of anti-inflammatory treatments has been taken in the case of covid-19 cytokines storm.

Cytokine antagonist

 The antagonist of cytokine block the receptor site so receptors would not be able to bind with particular cytokine this will stop the pathway of activation by cytokines of this soluble IL-2 receptor which is released in chronic T cell activation, can bind to IL-2 and thus this will now be unable to bind with membrane-bound receptor. This blocks the cytokine signal pathway.

 Some viruses also produce cytokine mimic for example Myxoma virus produce soluble gamma receptor

 Poxvirus produce soluble Gamma receptor

 Epstein Barr virus produces IL-10 homolog. 

PROBIOTICS : GOOD GUT BACTERIA, FOODS RICH IN PROBIOTICS ,WHAT KILLS GOOD GUT BACTERIA, INDIAN TRADITION OF PROBIOTICS

https://sciencezy.blogspot.com/2022/01/probiotics-good-gut-bacteria-foods-rich.html

In this article, we will learn about Probiotics, good gut bacteria, and what are the conditions that kill good gut bacteria. What are the foods that increase good gut bacteria naturally?

Probiotics are the food pro(life) biotics (organisms). These are the food preparations that have live microorganisms. These are not medications, these are food preparation. Probiotic food has a population of microorganisms that are friendly to our gut.

 We have a very old tradition of probiotics. In India, different regions have different probiotic foods. These are taken by the population to keep their gut healthy. 

 Principle behind probiotics

Our gut has a population of microorganisms, some of which are harmful and others being good. Serving a good population of live microorganisms through food can improve the overall health of people and this is the main principle of probiotics.

 We have a tradition of taking Lactobacillus through sour milk,  Yogurt (Dahi), Chhach.

Probiotics increase the good bacterial population naturally. The good bacteria eliminate or reduce the bad /pathogenic bacteria through ecological competition. 

Good bacteria help in increasing appetite 

 Cure inflammatory bowel, that causes pain in the belly.

  Good bacteria help in the metabolism of many food products.

GOOD GUT BACTERIA:

There is a community of microorganisms that are present in our gut. Some of which are listed here

BACTERIAL SPECIES OF GUT

Lactobacillus

Lactobacillus casei

Bifidobacterium

Enterococcus

Other microorganisms found in  probiotics

 Saccharomyces cerevisiae

Pichia anamola

Trichosporon spp

Candida tropicalis

WHAT KILLS GOOD GUT BACTERIA

 Antibiotics

  Antibiotics by principle, cannot distinguish between good and bad populations of microorganisms, they kill them all.

 Diarrhea

 Further, antibiotics cause diarrhea that eliminates the good bacteria population from the gut.

Chronic infectious diarrhea

 It is caused by bacteria, fungus, or viruses, it washes of good bacteria from the gut. Once cured the microbial population is established again by supplementation of probiotics in the diet.

 Alcohol also decreases good bacteria in the gut. 

Beverage, chocolate preparations with heavy added sugar are digested fast in the gut and thus do not allow the growth of good bacteria in the gut.

 Prebiotics: Foods that increase good gut microorganisms 

Some food items are known to be Prebiotics as they help in the growth of the population of microorganisms in the gut. The Prebiotics have carbohydrates (cellulose/lactose, etc) that are the food for microorganisms. These are green leafy vegetables, sour bread, raw seeds, sprouts.

RELATIONSHIP OF PROBIOTICS AND PREBIOTICS

  FOODS RICH IN PROBIOTICS: The Indian tradition of Probiotics 

In India we use pickles, which are preserved foods, they have enhanced taste, as well as they have a good population of microorganisms so these are traditional probiotics. 

The range of probiotics that are used in India as appetizers include

Lemonade, most common non-alcoholic drink used in India. If it does not have sugar, it is a probiotic.

 Koozh is a breakfast preparation used in Tamil Nadu made from millet and broken rice that is fermented in a pot. Koozh has Lactobacillus, Bifidobacterium, and Enterococcus population. 

 Toddy is used as an alcoholic beverage but fresh toddy is a Probiotic. It is the sap of a palm tree. It is the Probiotic preparation of Telangana State.

Kanji is used in North India. It is prepared from red carrot or purple carrot, beats, seasoned with mustard seed and spices. It is allowed to ferment for 3-4 days. Kanji is used as an appetizer.  It keeps the body warm in winter.

 Hamei is a rice fermented drink. It has 9 microbial species that have been so far identified. Species identified in this probiotic are Saccharomyces, Trichosporium species, Candida tropicalis, etc

 Hadiya another North Indian fermented food prepared from rice, it is also a probiotic

HOW GOOD PROBIOTICS ARE

Probiotics increase good microbiota in the gut.

They improve appetite

They improve the taste of food 

Cure irritable bowel symptoms

Cure inflammatory bowel symptoms

Improve digestion.

Decrease population of harmful microorganism

There is no fixed quantity of probiotics to 

 The health benefits of probiotics are a matter of research.

Further, the health benefits of probiotics are not universal. Old people and immunocompromised persons may show adverse effects of probiotics. So they should discontinue the use of probiotics.

Note: This is a knowledge-sharing platform. Information given here is not to be used for medical purposes. We do not use this platform for the promotion of any medical formations.

VITAMIN A : VITAMIN A, FOODS RICH IN VITAMIN A ,DEFICIENCY DISEASE, BIOLOGICAL ROLE OF VITAMIN A,VITAMIN A TOXICITY

What is vitamin A? What are the sources of vitamin A? What is the role of vitamin A in night vision? What is vitamin A toxicity?

Vitamin A(C20H30O) is the fat-soluble vitamin that is taken as nutrition in two forms the Preformed vitamin A and Provitamin A,  the preformed vitamin A consists of retinal esters and retinol, these are not further metabolized in the cell and are stored as such.

 Provitamin A consists of carotenoids.  These are converted into retinol, which is later on changed to retinoic acid, intracellularly.

VITAMIN  A: TYPES AND ITS INTRACELLULAR CONVERSION INTO RETINOIC ACID

As it is fat-soluble it is converted into micells and absorbed by duodenal mucosa in the intestine once absorbed, it is not washed away easily. It is stored in the liver and fat tissue. Deficiency of vitamin A can only be observed by a relative dose-response test where plasma retinol level is measured before and after an administration of a small dose of vitamin A.

BIOLOGICAL ROLE OF VITAMIN A

 It is involved in immune function.

It is required for healthy tooth formation

Proper cell division needs vitamin A

It is required for rhodopsin the pigment of the eye, so it is needed for night vision.

Pregnant ladies require  vitamin A for healthy childbirth

Lactating women also require vitamin A for child health.

Which foods are rich in vitamin A?

Preformed vitamin A is mainly found in animal sources such as beef liver, fish oil, milk, and egg. Pro-formed Vitamin A is found in green vegetables, orange, and yellow fruits.

TWO DIFFERENT FORMS OF VITAMIN A  AND THEIR SOURCES

Food rich in vitamin A

 Cod liver oil

 Sweet potato

 Carrot

 Beef liver

 Black Eyed Peas

Broccoli

 Bell pepper

Mango

 Yogurt

 Pumpkin pie

 Tomato juice

Cheese

Spinach

Deficiency of Vitamin A

Deficiency of Vitamin a results in dryness of the eye (Xerophthalmia)

 Deficiency of Vitamin A in pregnant ladies results in a high risk of  Nyctalopia or night blindness and reproductive disorders called teratogenesis.

Deficiency of Vitamin A in infants results in night blindness.

 Blurred vision

 Age-related macular degeneration is prevented and treated by vitamin A supplements. 

WHY DO WE GET VITAMIN A DEFICIENCY?

 

Cystic fibrosis: People with cystic fibrosis have a high risk of Vitamin A deficiency as they have impaired absorption of fats.

Preterm birth also leads to vitamin A deficiency as these infants do not have a fully formed liver.

Deficiency in infants is mainly due to not getting an adequate amount of colostrum or breast milk.

 In young children, deficiency occurs when they stop breastfeeding  

  People suffering from protein-calorie malnutrition and chronic diarrhea can suffer from vitamin A deficiency.

 How to reduce deficiency of vitamin A

The infant should be given breast milk, lactating women should take yellow fruits and vegetables.

 Prevented chronic diarrhea in children

 Avoid alcohol

 Avoid beverages with added sugar and sodium.

 Keep your pancreas healthy.

Keep your liver healthy.

Toxicity of vitamin A

 Excessive Vitamin a may lead to a fractured bone excessive, a dose of Vitamin A over the years tends  to become weak preformed Vitamin A mainly leads to Vitamin A toxicity it also leads to

nausea, headache,

pain joints and muscle pain. This is because Vitamin A is a fat-soluble vitamin, excess of vitamin A is stored in the liver and fat tissue, so it tends to accumulate over the years. Further, it does not wash away easily these symptoms continue for a long time even if you stop taking vitamin A supplements.

Vitamin A toxicity is observed when we take the excess of preformed vitamin A i.e. retinal and retinol. not in the case of beta carotenoid intake.

Note: This is a knowledge-sharing platform. Information given here is not to be used for medical purposes. We do not use this platform for the promotion of any medical formations.

 

 

Trusted Source list the recommended dietary allowances for vitamin A as 

Vitamin K: its structure, synthesis, role in biological processes and sources

Vitamin K: its structure, synthesis, role in biological processes and sources

 Vitamin K is a fat-soluble vitamin that belongs to a family of 2- methyl 1, 4 naphthoquinone and its derivative. Naturally occurring  Vitamin K has two subfamilies K1 and K2. Vitamin K is a factor in blood coagulation (koagulation -Danish). Vitamin K1 is also known as Phylloquinone

Vitamin K-2 Menaquinone family and named as  MK 1- MK 14 on the basis of the length of the isoprene chain.The isoperene may consists of alkane or alkyne R group i.e. saturated or unsaturated with tail length 1-14 methy group. K-3 is synthetic vitamin K known as menadione.

SYNTHESIS OF VITAMIN K

 Vitamin K1 is also known as Phylloquinone. It is naturally synthesized in plant green leaves.  It is mainly associated with the chloroplast of the plant cells and directly involved in photosynthesis.

 The other class of Vitamin K is vitamin K2 which is known as menaquinone. It is naturally produced by bacteria that are present in the gut of animals.

 Vitamin K-1 is naturally synthesized in plants. Leafy vegetables are a good source of vitamin K-1. Its digestion is similar to fat digestion, thus  it is converted in micells similar to fat molecules and absorbed endothelial cells large intestine. Vitamin K 2 is naturally produced by gut bacteria.

ROLE OF VITAMIN K

Vitamin K is used as a cofactor by vitamin K-dependent gamma-glutamate carboxylase. Vitamin K-1 is converted to vitamin K-2 in the liver and stored in the pancreas, soft tissue, muscles, and kidney. It is transported through the lymphatic system. It is released where it is required.  Phylloquinone is the inactive form of Vitamin K. Which is converted into an active form.

The process involves NADPH-dependent K reductase or vitamin K quinone reductase that converts QUINONE into QUINOL the active form of Vitamin K.quinol is used in carboxylation reaction and as a result of which it is oxidized to vitamin K 2,3- epoxide, that in turn reduced to a quinone.

 Active vitamin K is used by carboxylase enzymes for carboxylation of gla- protein. This carboxylation is done at the glutamic acid of the Gla-domain to produce Gamma glutamate. Gamma glutamate can bind with calcium ions and form calcium chelates. This binding results in  the proper folding of these proteins

 Gla protein present in human fall in the category of several categories such as

 Coagulation factors such as  prothrombin, factor VII, IX, X

Anticoagulating proteins S, C, Z

 Matrix gla-protein.

 Osteocalcin is also a gla protein that requires Vitamin K for its binding with calcium,  required for the proper mineralization of bones.

 

Thus vitamin K has found its role in blood coagulation

 The proper formation of soft tissue(cartilage)

 Bone mineralization etc.

 Sources of Vitamin K

 Green leafy vegetables.

Fermented food eg; cheese

 Dairy products

 Whole grain

Healthy oil

A good amount of vitamin K is found in green leaves instead of animal sources. Fermented foods have better availability of vitamin K.

DEFICIENCY OF VITAMIN K
WHAT HINDER THE PROPER FUNCTIONING OF VITAMIN K

Antibiotics, as they kill gut microflora

Anticoagulants like warfarin, are antagonistic to vitamin K

Alcohol consumption

What should be done

Keep your gut healthy.  

Avoid alcohol 

Reduce intake of beverages

Eat salad

 An adult person requires 30-80 micrograms of Vitamin K in a daily diet. Further in adults, no poisoning for excess of Vitamin K has been observed.

 Infants may have low vitamin K as it cannot cross the placenta.

 Breastfeed have a low amount of Vitamin K so infants are required to be injected with Vitamin K to protect them from fatal brain injury.

The deficiency of vitamin K results in hemorrhage.

Excessive bleeding.

Osteoporosis i.e. weak bones

Improper formation of soft tissue.

Beverages that have added sugar and sodium

Consume healthy oils 

Infants should be given Vitamin K injection. 

VITAMIN D( SOURCES, SYNTHESIS,AND DEFICIENCY DISEASE)

VITAMIN D

Vitamin D, it is also known as vitamin D2( C28H44O) ergocalciferol (calciferol), Vitamin D3(C27H44O)  (cholecalciferol).

 Vitamin D is a fat-soluble vitamin. It is known as Prehormone as it is the precursor of several metabolites.

HIGH-RISK POPULATION

The impact of vitamin D deficiency has been studied more than 300 years ago as a metabolic disorder Rickets. However, its relationship with vitamin D deficiency has been established only recently Vitamin D deficiency may be due to limited exposure to sunlight, dark skin, dietary deficiency, poor absorption of Vitamin D, gastrointestinal disease, and abnormality of Vitamin D metabolism,

The breastfeeding infants may also develop a deficiency of Vitamin D in absence of dietary supplements. The serum vitamin D is an indicator of deficiency of vitamin D in the body. 

People having milk allergy or lactose intolerance are prone to Vitamin D deficiency.

 

 

SYNTHESIS

 

Vitamin D is synthesized from cholesterol. it is synthesized naturally into the body.D2 is found in plants. D3 Cholecalciferol is animal Vitamin D. It is generated from 7 dihydroxy cholesterol in the skin during exposure to ultraviolet light. This precursor is then converted into active 25- hydroxyvitamin D is known as calcidiol in the liver. It is transported to the kidney where it is converted into calcitriol that is 1,25- Tri-hydroxy Vitamin D.

SYNTHESIS OF VITAMIN D, UNDER THE EXPOSURE TO SUNLIGHT

http://www.sciencezy.com

 Sources of Vitamin D

A large number of food items are a good source of vitamin D. Cod- liver, egg yolk, cheese has a good amount of D3.

 Mushrooms have D2 and if it is exposed to ultraviolet rays it will have increased availability of Vitamin D.

An animal-based dietary item such as beef or chicken has 2-18 times higher vitamin D.

The fortified milk also has an increased amount of Vitamin D.

 The uncovered skin’s exposure to ultraviolet rays can produce vitamin D naturally. However, sunscreens, clothing, and dark skin reduce the production of vitamin D.

 The sun exposure of skin for 5 to 30 minutes increases the Production of Vitamin D. 

WHAT IMPROVE VITAMIN D

Deficiency diseases

      Children having vitamin D deficiency develop Rickets.

   In adults and adolescence, vitamin D deficiency leads to osteomalacia, in which bones are incompletely or ineffectively mineralized, resulting in weak bones that result in pain. Vitamin D deficiency also results in hypocalcemia and dental abnormalities

      The breastfeeding infants develop vitamin D deficiency as human milk does not have a sufficient quantity of Vitamin D. Furthermore it is related to the mother’s level of Vitamin D.

     UV exposure is required for such infants to meet their daily requirement of Vitamin D.

· OLDER individuals are least exposed to UV rays so they may develop vitamin D deficiency. The dark skin people also have a high risk of Vitamin D deficiency.

 

 

 

 Why do we need Vitamin D

 

·         Vitamin D is required for normal calcium and phosphorous absorption in the body is required for the good health of our bones and muscles.

 Vitamin D also found its role in metabolism as it is required by beta cells of the pancreas to secrete insulin thus individuals may develop diabetes 2.

·         Vitamin D also regulates blood pressure thus it is linked to cardiovascular diseases.

·         People having enough serum vitamin D have a lower risk of cardiovascular diseases.

·         Vitamin D is involved in various brain processes.

·         Vitamin D receptors are present in neurons and it is known that they are associated with the pathophysiology of depression.

·         For healthy life get your daily dose of sunlight.

·         Get enough dairy products.

·         Animal food supplements give you a dietary option for vitamin D