Water Soluble Vitamins Flashcards
What are vitamins?
- Organic compounds that cannot be synthesized by humans and must be supplied by diet
- Required for functions like co-enzymes or as hormones
- Thirteen vitamins
- Classified based on solubilit
What are fat soluble vitamins?
• Absorption depends on normal fat digestion and absorption
• Maldigestion and malabsorption of dietary fats results in secondary
deficiency (bile duct obstruction, cystic fibrosis).
• Stored in liver (Vitamin K stored in least amounts)
What are the functions of fat soluble vitamins?
Vitamin A : Vision, epithelial tissue, growth
Vitamin D : Bone mineralization, blood calcium regulation
Vitamin E : Lipid soluble anti-oxidant
Vitamin K : Clotting factor synthesis; Coenzyme
What are the consequences of primary deficiency?
Primary deficiency
• Dietary deficiency
• Starvation
• Malnutrition
Explain secondary vitamin deficiency
Secondary deficiency
• Reduced intake
• Dental problems, chronic disease, morning sickness
- Malabsorption
- Diarrhea, genetic defects
- Post-bariatric surgery
- Increased requirements
- Pregnancy, post-operative, periods of rapid growth
- Increased loss
- Lactation
Whaat are the characteristics of water soluble vitamins?
- Daily supplements (not stored, except vitamin B12)
- Do not require bile salts and chylomicrons for absorption (Absorption easier than fat soluble vitamins)
- Toxicity not common (excess excreted in urine)
What is the significance of ascorbic acid (vitamin C)?
• Water soluble vitamin
• Connective tissue (collagen synthesis) and wound healing
– Prolyl and lysyl hydroxylase coenzyme – Hydrogen bond formation →
Collagen stability
• Absorption of iron
– Ferrous state
– Low dietary vitamin C → Microcytic anemia (reduced iron absorption) • Water soluble anti-oxidant: Free radical scavenger
– Antioxidant vitamins C, E and beta-carotene (provitamin A)
• Reduce chronic disease
What is scurvy?
- Perifollicular hemorrhages (Fragile blood vessels)
- Sore, spongy gums: Bleeding gums
- Loose teeth
- Bleeding into joints
- Frequent bruising
- Impaired/ delayed wound healing
Connective tissue defects (decreased hydroxyl groups): fewer H-bonds in collagen
Similar to vitamin K deficiency – Molecular mechanism for increased bleeding tendency is very different!!!!
What is the earliest sign of scurvy?
Perifollicular hemorrhages
What are the parts of the vitamin B complex?
- Thiamine (B1)
- Riboflavin (B2)
- Niacin (B3)
- Pantothenic acid (Coenzyme A) (B5)
- Pyridoxine (B6)
- Biotin (B7)
- Folic acid (B9)
- Cobalamin (B12)
Water soluble vitamins NOT stored – daily supplements essential (Vitamin B12 stored in liver)
What is the coenzyme of vitamin B1? What is the function?
• Coenzyme: TPP (Thiamine pyrophosphate)
• Coenzyme
– Oxidative decarboxylation of alpha-keto acids – maintains nerve
tissue (PDH complex, α-ketoglutarate dehydrogenase, branched chain
α-keto acid dehydrogenase)
– Transketolase in pentose phosphate pathway (HMP shunt)
– B1 supplementation Maple syrup urine disease (MSUD)***
What are the dietary sources of vitamin B1/thiamine?
• Dietary Sources:
– Widely available in diet BUT
– Deficient in Refined foods like polished rice, white flour, white sugar
What reactions require TPP?
Branched chain amino acid —>Branched chain keto acid
MSUD —>
Branched chain keto acid dehydrogenase
TPP
Branched chain metabolites
What are the consequences of thiamine deficiency?
Beriberi
• Polished rice is staple
• Affects aerobic tissues (Brain and cardiac muscle)
• Polyneuropathy: Disruption of motor, sensory and reflex
arcs; progress to paralysis (Dry beri beri)
• Cardiovascular:Cardiacfailure(Wetberiberi)
• Laboratorytests
– Low erythrocyte transketolase activity
– Serum thiamine levels
Pedal edema in wet beriberi
Wernicke-Korsakoff syndrome
Wernicke - Korsakoff syndrome:
• Devastating neurologic complication in chronic alcoholics
• Ophthalmoplegia and nystagmus (to and fro eyeball movement)
• Ataxia, confusion, disorientation and loss of memory
• Confabulation
What are the coenzyme forms of vitamin B2?
Riboflavin
• Coenzyme forms
– Flavin mononucleotide (FMN)
– Flavin adenine dinucleotide (FAD)
• Oxidation-reduction reactions of TCA cycle, beta oxidation (Succinate dehydrogenase, PDH, Acyl CoA DH…..)
Describe riboflavin deficiency (vitamin B2)
• Nutritional
Signs and symptoms
- Cheilosis – areas of pallor, cracks and fissures at angles of mouth
- Glossitis – inflammation and atrophy of tongue
- Facial dermatitis
What are the coenzyme forms of vitamin B3 (niacin)?
• Coenzyme forms
– NAD+
– NADP+
VITAMIN B3 (NIACIN)
• Coenzymes in oxidation-reduction reactions
– NAD+ – Dehydrogenases (PDH, alpha-ketoglutarate dehydrogenase, malate
dehydrogenase, …..)
– NADP+ – HMP shunt and fatty acid and cholesterol synthesis (G6PD, HMG
CoA reductase, …)
• Therapeutic uses:
– Inhibits adipose tissue lipolysis and reduces free fatty acids: Type IIb
hyperlipoproteinemi
Describe niacin deficiency
Pellagra (rough skin): 3Ds
• Dermatitis (skin)
– Exposed areas of body
– Redness, thickening and roughening of skin
• Diarrhea (GIT)
• Dementia (CNS)
– Neuron degeneration in brain and spinal tracts
– Loss of memory
• Death
Describe pellagra dermatitis
‘Necklace like’ and hands and legs
Describe the significance of tryptophan as a precursor of NAD+
• Tryptophan forms NAD+ and NADP+ (refer amino acid metabolism)
• Risk factors for Niacin deficiency (Pellagra)
– Corn based diets (Niacin and tryptophan deficient)
– Hartnup disease (Neutral amino acid transporter defect)* -
Dietary niacin supplements
– Carcinoid syndrome* (excessive tryptophan to serotonin
conversion; less tryptophan for NAD formation)
What is the significance of biotin?
- Carboxylation reactions
- Multiple carboxylase deficiency***: Defect in incorporating biotin
- Coenzyme for:
- Pyruvate carboxylase (gluconeogenesis) – Impaired gluconeogenesis
- Acetyl-CoA carboxylase (fatty acid synthesis) – Hair loss and dermatitis
- Propionyl-CoA carboxylase (Conversion of propionyl CoA to methylmalonyl
CoA) – High serum propionate levels
• Avidin (raw egg white), inhibits biotin absorption
Discuss isoniazid therapy as a risk of pyridoxine deficiency
• Isoniazid (anti-tuberculosis drug)
– Inactivates pyridoxine
– Pyridoxine supplements given with INH
– Peripheral neuropathy: Adverse effect if B6 supplements not administered
What are the manifestations of pyridoxine deficiency?
- Microcytic anemia (Reduced heme synthesis due to low ALA synthase activity)
- Peripheral neuropathy (Reduced neurotransmitter formation)
• Increased cardiovascular disease risk (high plasma homocysteine
levels)
• Seizures in infants (Reduced neurotransmitter formation)
Explain the two reactions of vitamin B12 is used for
- Methionine synthase
– Converts methyl tetrahydrofolate to tetrahydrofolate: Required for DNA synthesis
– In B12 deficiency, methyltetrahydrofolate trap (folate trap): Macrocytic anemia - Methylmalonyl CoA mutase
• Amino acids and odd-chain fatty acid metabolism forms propionyl CoA
• Elevated serum methylmalonate
• Methylmalonate results in neurological
manifestations: Interferes with myelin formation • Vit B12 supplements in inherited methylmalonic
aciduria**
Describe the ansorption of vitamin B12
- Animal products; Vegans risk of deficiency
- Intrinsic factor (IF) by gastric parietal cells for Vit B12 absorption; Achlorhydria (risk factor)
- Parietal cell destruction due to autoantibodies - Lack of IF – Poor B12 absorption - Pernicious anemia
- IF-B12 complex absorbed in terminal ileum
What are the risk factors of vitamin B12 deficiency?
– Lack of intrinsic factor (IF): Pernicious anemia, After Bariatric surgery
– Ileal mucosal disease
What are the risk factors of vitamin B12 deficiency?
– Lack of intrinsic factor (IF): Pernicious anemia, After Bariatric surgery
– Ileal mucosal disease
What are the clinical features of deficiency of vitamin B12?
Clinical features:
• Macrocytic megaloblastic anemia
– Macrocytes in peripheral blood film
– Megaloblasts in bone marrow (megaloblastic anemia) – Secondary to folate deficiency (folate trap)
• Neuropsychiatric symptoms
– Tingling and numbness in extremities; Psychiatric manifestations
– Myelin degeneration in motor and sensory pathways due to
methylmalonate
What is the significance of folic acid?
• FH4 receives 1-carbon groups from amino acids
• Uses 1-C groups for purine and pyrimidine synthesis (thymidylate
synthesis) (DNA synthesis)
• Methyl THF → THF requires Vitamin B12 (Methionine synthase
What are the symptoms of folic acid deficiency?
- Dietary lack of green leafy vegetables
- Impaired absorption (Intestinal mucosal disease)
- Increased requirement as in pregnancy
- Folate antagonists: Methotrexate (inhibitor of dihydrofolate reductase)
- Folate trapping due to B12 deficiency
• Macrocytic megaloblastic anemia • Macrocytes in peripheral blood smear • Megaloblasts in bone marrow • NO neurological features – Methylmalonate levels are normal
Compare maacrocytic anemias in vitamin B12 and folate deficiency
Vitamin B12 deficiency
• Clinical features: Anemia with associated neurological features
• Anemia – Macrocytic (MCV increased) and megaloblastic bone marrow
• Serum homocysteine and serum methylmalonate levels are elevated
• Anemia is due to folate trap
• Neurological features due to accumulation
of methylmalonate (affects myelination)
• Risk factors: Parietal cell destruction (pernicious anemia); ileal mucosal disease or resection; vegan diet
• Serum vitamin B12 levels are low
Folate deficiency • Clinical features: Macrocytic anemia • Anemia – Macrocytic (MCV increased) and megaloblastic bone marrow • Serum homocysteine levels are elevated; Serum methylmalonate levels are normal • Anemia is due to folate deficiency • NO neurological features • Risk factors: pregnancy, malabsorption syndrome, folate antagonist treatment • Serum folate levels are low
How is megaloblastic anemia treated?
Treatment of megaloblastic anemia:
Combination of folic acid and cobalamin
Refer: Vit B12 and folic acid lecture for differences between Folic acid and vit B12 deficiency
What is the significance of folic acid during pregnancy?
- Folate requirement increases during pregnancy
- Rapidly dividing fetal cells vulnerable to folate deficiency
- High incidence of fetal neural tube defects (Spina bifida and anencephaly)
- Supplements at time of conception and during first trimester
