Vitamins Flashcards
Vitamin present only in animal diet
B12
Marker of vitamin B2 def
Glutathione reductase activity
Vitamin syn by bacteria
B2,B5 , B7 ,K
Functions of PLP
- Transamination
- Decarboxylations
- Heme metabolism
- Sulphur metabolism(2 steps)
- Glycogenolysis ( phosphorylase)
- Niacin synthesis( kynureninase)
Vitamin B6 marker
Transaminase
Simple decarboxylation
Protein metabolism
Glycogen phosphorylase
Deficiency manifestations of B6 deficiency
- Reversible peripheral neuritis ( decarboxylation )
- Pellagra ( niacin deficiency)
- Hypochromic microcytic anaemia
- Homocystinuria
- Xanthurenic aciduria
B6 RDA
Adults 1 - 2 mg/day
Pregnancy and lactation 2.5
Two atypical vitamin
Niacin B3 and D3
Why is zinc important for retinol metabolism
Zinc is a part of alcohol dehydrogenase to convert retinal to retinol
Other functions of vitamin A (carotenoids)
- Like a hormone in tissue differentiation
- Reproduction ( retinol )
- Antioxidant
- Skin health ( against psoriasis)
- Against heart diseases
Deficiency manifestations of vitamin A
- Bitots spots in conjunctiva
- Keratomalacia (corneal ulcer)
- Preventable blindness
- Skin and mucous membrane lesions
- Night blindness and xerophthalmia
Most common vitamin deficiency
Daily dosage of vitamin A
Children 400- 600 microgram/day
Women 750
Men 750 - 1000
Pregnancy 1000
Richest sources are halibut liver oil, fish oil
Vitamin D requirement
Children 10 microgram/day or 400 IU
Adults 5 - 10
Pregnancy, lactation 10
Old age 15
Functions of vitamin E
- Antioxidant
- Against hemolysis
- Anti aging
- Against atherosclerosis
Vitamin E and selenium
Glutathione peroxidase and Vitamin E are synergistic in preventing lipid peroxidation.
RDA of vitamin E
Males 10mg/day
Females 8
Pregnancy 10
Lactation 12
Clotting factors activated by vitamin K
2 prothrombin 7 SPCA 9 Christmas factor 10 Stuart prower factor Via gamma carboxylation of glutamic acid residues
RDA of vitamin K
50 - 100 mg/day
Deficiency rare , except in preterm babies
Earliest manifestation of vitamin B1 or thiamine
RDA of thiamine
Decreased Erythrocyte transketolase activity
1 - 1.5 mg/day (depends on calorie intake)
Functions of FMN
- Amino acid oxidation O2 to H2O2
2. In respiratory chain in between NAD+ & CoQ
FAD dependent enzymes
- Succinate to fumarate by succinate dehydrogenase
- Acyl Co-A dehydrogenase on acyl Co-A
- Xanthine to uric acid by xanthine oxidase
- Pyruvate dehydrogenase & alpha keto glutarate dehydrogenase
NADPH generating reactions
- G-6-PD in HMP
- 6-Phosphogluconate dehydrogenase in HMP
- Cytoplasmic isocitrate dehydrogenase
- Malic enzyme
NADPH utilising reactions
- Beta keto acyl ACP dehydrogenase
- Alpha, BetaUnsaturated acyl AC to. acyl ACP
- HMG CoA-Reductase
- Folate reductase
- Phenylalanine hydroxylase ( to tyrosine)
- Meth Hb to Hb
Pellagra is found more in ______gender
It’s features
Females due to inhibitory influence of estrogen on tryptophan metabolism
- Dermatitis (cassals necklace)
- Diarrhoea
- Dementia
Daily requirement of niacin
20mg
5mg higher during lactation
Panthothenic acid(pan =>everywhere )
Co-A
Deficiency (rare) => Gopalan burning foot syndrome
RDA 10mg/day
Biotin requiring carbon fixation reactions
- Acetyl Co-A carboxylase in FA biosynthesis
- Propionyl Co-A carboxylase
- Pyruvate carboxylase for OAA synthesis(TCA) and for gluconeogenesis
Carboxylation reactions where biotin is NOT required
- CPS 1 and 2 for urea and pyrimidine synthesis
- C6 of purine
- Malic enzyme
Biotin cycle
Holocarboxylase synthetase + biotinidase
Deficiency
Multiple carboxylase Deficiency
CNS involvements
Tomcat urine odour
Hair and skin disorder
Raw eggs and biotin
Has Avidin which binds to B7
Pyruvate carboxylase decreases
Hypoglycaemia
Rx B7
RDA of biotin B7
200-300mg/day
Folic acid is absorbed in _____
Upper parts of jejunum ,transported through blood via beta globulins
Causes of folate deficiency (one of the most common )
- Pregnancy
- Drugs
- Defective absorption
- Haemolytic anaemia (demand increases)
- Dietary deficiency
- Folate trap(B12 deficiency)
Holocarboxylase
Bit B7(biotin ) + carboxylase
Manifestations of folate deficiency
- DNA synthesis Decreases (thymine synthesis decreases )
- Macrocytic anaemia (not megaloblastic and without neurological symptoms )
- Hyperhomocysteinuria which leads to
- Birth defects
- Cancer
Assessment of folate deficiency
- Blood level
- Histidine load test( FIGLU test)
- AICAR excretion test( pyrimidine synthesis decreases )
- Peripheral blood press
RDA of folate
Adults 200 mg/day
Pregnancy 400 mg/day
Lactation 300 mg/day
Eg of anti vitamins
Dicoumarol
Methotrexate (folic acid)
Isoniazid (pyridoxine)
Forms of B12
Oral(lab) :cyano Injections :hydroxy Functional forms are Storage: DeoxyAdenosyl (liver , somatic) Transport(blood) :Methyl
Second factor of B12 or cobalophilin is secreted from
Saliva
Functions of vitamin B12
- Methyl Malonate Co-A isomerase of odd chain fatty acids
- Methionine synthase or homocysteine methyl transferase
- Demethylation of methyl THFA
Causes of vitamin B12 deficiency
- Diet
- Decreased absorption
- Addisonian pernicious anaemia
- Gastric atrophy
- Pregnancy
- Fish tapeworm
Deficiency manifestations of vitamin B12
- Folate trap
- Megaloblastic anaemia
- Homocysteinuria
- Demyelination due to SAM
- Subacute combined degeneration
- Achlorhydria
Assessment of vitamin B12 deficiency
- Serum B12 levels
- Schilling test
- Methyl malonic acid
- Blood smear
- Homocysteinuria
- FIGLU test
RDA of B12
1-2 microgram/day
2 microgram/day for pregnancy and lactation
Functions of vitamin C
- Redox and antioxidant
- Hydroxylation of proline and lysine for collagen
- Hydroxylation of tryptophan for serotonin
- Tyrosine metabolism
- Iron absorption via reduction
- MetHb reduction
- Helping folate reductase( thus RBC maturation )
- Steroidogenesis
- Stimulates phagocytosis
- Cataract
Barlow disease
Infantile scurvy
Vitamin C supplementation required between 6 & 12 months ( Breast milk)
Vitamin C deficiency and anaemia ?
Microcytic hypochromic anaemia due to
- Loss of blood via haemorrhage
- Decreased Iron absorption
- Decreased THFA
- Increased MethHb
RDA of vitamin C
75mg/day
Pregnancy and lactation 100mg/day
For smokers and those on contraceptive pills
> 100 mg/day
Toxic water soluble vitamins are
Vitamin B6 and niacin
Retinoids are found in __ sources
Animal
Eg of carotenoids
Lutein, zeaxanthin(Rx of macular degeneration )
Lycopene (Rx of prostate cancer)
Beta carotene ( antioxidant )
Different forms of retinoids acid
All trans
9 cis
13 cis
In regulation of gene expression (growth and development ,
Tissue differentiation)
Retinol structure
Beta ionone ring + isoprenoid chain
Absorption and storage of vitamin A
Retinol ester is split and retinol is absorbed
Deoxygenase of intestinal cells split absorbed carotenoid
These are esterified in these cells
The retinal esters are carried by chylomicron
In the liver they are stored in the peri sinusoidal cells (Ito cells)
Vitamin A is transported in the form of a
Ternary complex
Retinol + RBP + Transthyretin
Metarhodopsin II
It activates the signal cascade pathway
GPCR-transducin is activated Phosphodiesterase activated cGMP to 5’GMP closes Na+ channel Hyperpolarisation
RAR
Retinoids acid receptor
All trans retinoids acid ligand
RXR. Why vitamin D or thyroid deficiency causes vitamin A deficiency
Retinoic acid X receptor
9 cis retinoic acid
It dimerises with vitamin D receptor complex,(thyroid hormone complex,…)
Heterodimer
Then binds
Earliest sign (not symptom)of Vitamin A deficiency
Loss of sensitivity to green light
Earliest symptom is nyctalopia
Skin effects of vitamin A deficiency
Follicular hyperkeratosis (phrynoderma or toad skin) Also caused by EFA deficiency
Squamous metaplasia( UTI & RTI)
Blockage of adnexal glands
Toxicity of vitamin A
Rare
Seen in arctic explorers due to polar bear liver
Affects lysosomes
Acute
1 pseudotumor cerebri (head ache, vomitting,blurry vision)
2 exfoliating dermatitis
Chronic
Weight loss ,nausea, bony exostosis,
Joint pain, increases osteoclastic activity(hip fractures)
Therapeutic application of vitamin A
Beta carotene( cutaneous photosensitivity) 2. All trans retinoic acid( tretinoin)- mild acne, acute promylocytic leukaemia ( differentiation therapy)
13cis retinoic acid
Isotretinoin
Teratogenic
Used in cystic acne(severe) , childhood neuroblastoma
Vitamin D eg
Vitamin D2 ergocalciferol (plant origin)
Vitamin D3 cholecalciferol (calciol)
Dietary source of vitamin D is
Fish (Halibut liver oil)
Vitamin D fortified
Rest is negligible
Transport protein of D3 and the first hydroxylation
D Binding Protein(DBP)
which goes to the liver where it is hydroxylated by 25 Hydroxylase (part of cytochrome p450) to calcidiol or 25 OH D3
Hydroxylation in the kidney of calcidiol
By 1 alpha hydroxylase (favoured by PTH)
it is converted to 1,25 dihydroxy cholecalciferol or calcitriol
This is the RDS
UV. light responsible for isomerisatiom of 7 dehydrocholesterol to cholecalciferol
UV -B
290-315 nm
Inactivation of calcidiol and calcitriol is by
24 hydroxylation to
24 calcidiol and calcitetrol
Functions of vitamin D
- Regulation of Ca and P
- Immunomodulatory
- Antiproliferative
- Bone mineralization during bone development
Phosphorus level in serum increasing substances
Vitamin D
Regulation of Ca in intestine
Vitamin D increases
- Calcium transport channel TRPV6
- calbindin 9K
Regulation of Ca in kidneys
PTH increases hydroxylation of calcidiol in DCT
Vitamin D then increases
1. TRPV 5
2. Calbindin 28K
Thus increases both Ca and P reabsorption
But PTH increases excretion of P while increasing Ca reabsorption
Regulation of Ca in bones by vitamin D and PTH
Increases action of RANK ligand (receptor activator NFKB Ligand) located on osteoblasts
Whose receptor is located on proosteoclasts
Thus increases maturation of osteoclasts
Vitamin D and tuberculosis
Few I alpha hydrxylation occurs in the macrophages by cytochrome p27B
Toll like receptor binds to the bacteria which increases cytochrome p27B
Calcitriol increases which increases cathelicidin which kills the bacteria
Holy grail of cancer medicine is vitamin D
If vitamin D level is less than 20 no/ml it is associated with increased colon,breast and prostate cancers
It is also protective against prediabetes and metabolic syndrome
Contrary to normal state vitamin D during bone development increases
- Osteoclastic activity
- Mineralisation of bone
- Osteocalcin (mineralization)
Thus vitamin D deficiency during infant causes poor mineralization of osteoid leading to rickets
Rickets
Rachitic rosary
Wind swept deformity
Harrison’s sulcus
Nutritional rickets
Nutritional deficiency or decreased sunlight exposure Serum Ca decreases But, Secondary hyperparathyroidism 1 alpha hydroxylation increases Then vitamin D3 is normalised Then serum Ca is normalised But serum phosphate level will be reduced
Toxicity of vitamin D
4000 IU
in infants > 50 mg/day
Deposition of Ca in soft tissues and blood vessels
(contraction of blood vessels and hypertension)
Metastatic calcification
Calcinosis
Assay of vitamin D
25 hydroxy cholecalciferol
Ideal level 20-100 ng/mL
Serum osteocalcin
Vitamin E most potent active form is
Alpha tocopherol
Vitamin E has chromate ring with isoprenoid unit (seen in A,E,K)
Antioxidant Functions of vitamin E
- Chain breaking antioxidant
- Prevents oxidation of PUFA in the membrane
- Prevents oxidation of LDL
Deficiency manifestations of Vitamin E
- Axonal degeneration (posterior column affected and hence decreased position and vibration sense)
- Spinocerebellar symptoms (ataxia)
- Peripheral neuropathy
- Skeletal myopathy
- Pigmented retinopathy
- Ophthalmoplegia
Features of the least toxic fat soluble vitamin
Vitamin E
- Decreases platelet aggregation
- Interferes with vitamin K
Sources of vitamin E
Wheat germ oil
Cotton seed oil
Sunflower oil
High doses of vitamin E is used for
- Retrolentil fibroplasia
- Bronchopulmonary dysplasia
- Intraventricular haemorrhage
- Intermittent claudication
Structure of vitamin K
Naphthoquinone derivative + isoprenoid chain
Forms of vitamin K
K1 phylloquinone plant sources
K2 Menaquinone intestinal flora
K3 menadione synthetic - water soluble form of a fat soluble vitamin
Action of vitamin K on clotting factors
Vitamin K gamma carboxylase 2,7,9,10 for Ca binding and itself is converted to vitamin K epoxide.
It is converted back by vitamin K epoxide reductase ( inhibited by warfarin, dicoumarol)
Proteins that are affected by vitamin K (gamma carboxylation)
- Protein C, protein S
- Osteocalcin and nephrocalcin
- Product of gas 6 gene (gene arrest specific)
- Matrix gla protein
ABC enzymes
ATP dependent Biotin Carboxylation
Deficiency of vitamin K
Increases
- Bleeding time
- Prothrombin time
Reasons why vitamin K deficiency occurs in premature infants
- Immaturity of liver
- Sterile gut
- Breast milk poor in vitamin K
- Poor placental transport
- Low body stores
Increased vitamin K causes
Hemolysis ( deficiency of vitamin E causes the same)
Jaundice
Hyperbilirubinemia
Kernicterus and brain damage