water soluble vitamins lecture for 1st year mbbs by dr sadia haroon
TRANSCRIPT
The Water-Soluble Vitamins
Overview of Water-Soluble Vitamins
• Dissolve in water
• Generally readily excreted
• Subject to cooking losses
• Function as a coenzyme
• Participate in energy metabolism
• 50-90% of B vitamins are absorbed
• Marginal deficiency more common
Enrichment Act of 1941 and 1998
• Many nutrients lost through milling process of grains
• Grain/cereal products are enriched
• Thiamin, riboflavin, niacin, folate, iron
• Whole grains contain original nutrients
• Enriched grains still deficient in B-6, magnesium and zinc
Thiamin
• Contains sulfur and nitrogen group
• Destroyed by alkaline and heat
• Coenzyme: Thiamin pyrophosphate (TPP)
Food Sources of Thiamin
• Wide variety of food
• White bread, pork, hot dogs, luncheon meat, cold cereal
• Enriched grains/ whole grains
• Thiaminase found in raw fish
Absorption, Transport, Metabolism of Thiamin
• Absorbed in the jejunum by a carrier-mediated system
• Transported by RBC in the blood
• Excess quickly excreted in the urine
Function of Thiamin (Fig. 10-2)
Coenzyme: Thiamin Pyrophosphate (TPP)
• Synthesis of neurotransmitter
• Convert pyruvate to acetyl-CoA CoA NAD+ NADH + H+
Glucose Pyruvate Acetyl-CoA Citric
CO2 Acid Cycle
RDA For Thiamin
• 1.1 mg/day for women
• 1.2 mg/day for men
• Most exceed RDA in diet
• Surplus is rapidly lost in urine; non toxic
Who is at Risk For Deficiency?
• Poor
• Alcoholics
• Elderly
• Diet consisting of highly processed foods
Deficiency of Thiamin
• Occurs where rice is the only staple
• Dry beriberi– Weakness, nerve degeneration, irritability, poor
arm/leg coordination, loss of nerve transmission
• Wet beriberi– Edema, enlarge heart, heart failure
Riboflavin
• Coenzymes:– Flavin mononucleotide (FMN)– Flavin adenine dinucleotide (FAD)
• Oxidation-reduction reactions
• Electron transport chain
• Citric Acid Cycle
• Catabolism of fatty acids
Food Sources of Riboflavin
• Milk/products
• Enriched grains
• Liver
• Oyster
• Brewer’s yeast
• Sensitive to uv radiation (sunlight)
• Stored in paper, opaque plastic containers
Absorption, Transport, & Metabolism of Riboflavin
• HCL in the stomach release riboflavin from its bound forms
• Absorption– Active or facilitated transport during low to
moderate intake– Passive absorption during high intake– Increase with intake
• Transported by a protein carrier in the blood
Functions of Riboflavin
• Accepts electrons Electron Transport Chain
FAD FADH2
Succinate Fumarate Citric Acid Cycle
• Participates in beta oxidation• FMN shuttles hydrogen ions and electrons to into
the electron transport chain
RDA for Riboflavin
• 1.1 mg/day for women
• 1.3 mg/day for men
• Average intake is above RDA
• Toxicity not documented
Who is at Risk For Deficiency?
– Rare– Low milk/dairy intake– Alcoholics– Long term phenobarbital use
Deficiency of Riboflavin
• Ariboflavinosis– Glossitis, cheilosis, seborrheic dermatitis,
stomatitis, eye disorder, throat disorder, nervous system disorder
• Occurs within 2 months
• Usually in combination with other deficiencies
Glossitis (Fig. 10-4)
Niacin
• Nicotinic acid (niacin) & nicotinamide (niacinamide)
• Coenzyme– Nicotinamide adenine dinucleotide (NAD)– Nicotinamide adenine dinucleotide phosphate
(NADP)• Oxidation-reduction reaction• Metabolic reactions
Food Sources of Niacin
• Mushrooms
• Enriched grains
• Beef, chicken, turkey, fish
• Heat stable; little cooking loss
Absorption, Transport and Storage of Niacin
• Readily absorbed from the stomach and small intestine
• Absorption: active transport and passive diffusion
• Transported from the liver to all of the tissues where it is converted to the coenzymes
Functions of Niacin• NAD and NADP participates in 200+ reactions in the body
2 NAD+ 2NADH + H+
Glucose Pyruvate
NAD+ NADH + H+
Pyruvate Lactate
NAD+ NADH + H+
Isocitrate Alpha-ketogluterate NAD+ NADH + H+ Alpha-ketogluterate Succinyl CoA NAD+ NADH + H+
Malate Oxaloacetate
• Electron transport chain
Citric Acid Cycle
RDA for Niacin
• 14 NE/day for women
• 16 NE/day for men
Deficiency of Niacin• Pellagra
– 3 Ds – Occurs in 50-60 days– Decrease appetite & weight
• Prevented with an adequate protein diet• Enrichment Act of 1941• Only dietary deficiency disease to reach epidemic
proportions in the U.S.• Who is at risk?
– (Untreated) corn as main staple, poor diet, Hartnup disease, alcoholics
Dermatitis of Pellegra (Fig. 10-5)
Niacin as a Medicine
• 75-100 x RDA can lower LDL and TG and increase HDL
• Slow/ reverse progression of atheroscelerosis with diet and exercise
• Toxicity effects– Flushing of skin, itching, nausea, liver damage
Pantothenic Acid• Part of Coenzyme-A• Essential for metabolism of CHO, fat,
protein
Glucose
Fatty acids Acetyl-CoA Amino Acids
Alcohol
Food Sources of Pantothenic acid
• Meat• Milk• Mushroom• Liver• Peanut• Adequate Intake = 5 mg/day• Average intake meets AI
Deficiency of Pantothenic Acid
• Rare• Burning foot syndrome, listlessness,
fatigue, headache, sleep disturbance, nausea, abdominal distress
• Alcoholics at risk• Usually in combination with other
deficiencies
Biotin
• Free and bound form
• Biocytin (protein bound form)
• Biotinidase in small intestine
• Metabolism of CHO, fat, protein (C skeleton)
• DNA synthesis
Food Sources of Biotin• Cauliflower, yolk, liver, peanuts, cheese• Intestinal synthesis of biotin• Biotin content only available for a small number
of foods• Unsure as to bioavailablity of synthesized biotin• We excrete more than we consume• Avidin inhibits absorption
– > a dozen of raw eggs a day to cause this effect
Functions of Biotin
• Assists in the addition of CO2 to substances• Carboxylation of acetyl-CoA to form malonyl-
CoA for the elongation of a fatty acid chain• Addition of CO2 to pyruvate to yield
oxaloacetate• Breaks down leucine• Allows 3 essential amino acids to be oxidized
for energy
Biotin Needs
• Adequate Intake is 30 ug/day for adults
• This may overestimate the amount needed for adults
• No Upper Limit for biotin
Who is at Risk For Deficiency?
• Rare• High intake of raw egg white diet• Alcoholics• Biotinidase deficiency• Anticonvulsant drug use• Signs & symptoms: skin rash, hair loss,
convulsion, neurological disorders, impaired growth in children
Vitamin B-6: Pyridoxal, Pyridoxine, Pyridoxamine
• Main coenzyme form: pyridoxal phosphate (PLP)
• Activate enzymes needed for metabolism of CHO, fat , protein
• Transamination• Synthesis of hemoglobin and oxygen binding
and white blood cells• Synthesis of neurotransmitters
Food Sources of Vitamin B-6
• Meat, fish, poultry
• Whole grains (not enriched back)
• Banana
• Spinach
• Avocado
• Potato
• Heat and alkaline sensitive
Absorption and Metabolism of Vitamin B-6
• Absorbed passively
• All three forms of B-6 are phosphorylated in the liver
• Binds to albumin for transport in the blood
• B-6 is stored in the liver and muscle tissue
• Excess is excreted in urine
Functions of Vitamin B-6• Participates in 100+ enzymatic reactions• Decarboxylation of amino acid (decarboxylase)• Transamination reaction (transaminase)• Structural rearrangement of amino acids (racemase)• RBC synthesis• CHO metabolism• Lipid metabolism• Neurotransmitter Synthesis• Conversion of tryptophan to niacin
RDA for Vitamin B-6
• 1.3 mg/day for adults
• 1.7 mg/day for men over 50
• 1.5 mg/day for women over 50
• Daily Value set at 2 mg
• Average intake is more than the RDA
Deficiency of Vitamin B-6• Microcytic hypochromic anemia• Seborrheic dermatitis• Convulsion, depression, confusion• Reduce immune response• Peripheral nerve damage• Who is at risk?
– Elderly– Alcoholics
• Alcohol decreases absorption• Destroy the coenzyme form
B-6 As A Medicine?
• PMS– B-6 to increase the level of serotonin– Improve depression– Not a reliable treatment
• Carpal tunnel syndrome• Toxicity potential• Can lead to irreversible nerve damage with >
200 mg/day
Folate (Folic acid, Folacin)
• Consists of pteridine group, para-aminobenzoic acid (PABA), and glutamic acid
• Coenzyme form: tetrahydorfolic acid (THFA)
Food Sources of Folate
• Liver
• Fortified breakfast cereals
• Grains, legumes
• Foliage vegetables
• Susceptible to heat, oxidation, ultraviolet light
Absorption, Metabolism of Folate
• Absorbed in the monoglutamate form with help of folate conjugase
• Actively absorbed during low to moderate intake• Passively absorbed during high intake• Delivered to the liver where it is changed back to
the polyglutamate form• Mostly stored in the liver• Excreted in the urine and bile (enterohepatic circulation)
Functions of Folate
• DNA synthesis– Transfer of single carbon units– Synthesis of adenine and guanine– Anticancer drug methotrexate
• Homocysteine metabolism
• Neurotransmitter formation
RDA for Folate
• 400 ug/day for adults
• Daily Value is set at 400 ug
Deficiency of Folate
• Similar signs and symptoms of vitamin B-12 deficiency
• Pregnant women
• Alcoholics– Interferes with the enterohepatic circulation of
bile/folate
Megaloblastic Anemia (Fig. 10-7)
Neural Tube Defects
• Spina bifida• Anencephaly• Importance of folate
before and during pregnancy
(Fig. 10-8)
Toxicity of Folate
• Epilepsy
• Skin, respiratory disorder
• FDA limits nonprescription supplements to 400 ug per tablet for non-pregnant adults
• OTC Prenatal supplement contains 800 ug
• Excess can mask vitamin B-12 deficiency
Vitamin B-12
• Cyanocobalamin. methlcobalamin,
5-deoxyadenosylcobalamin
• Contains cobalt
• Folate metabolism
• Maintenance of the myelin sheaths
• Rearrange 3-carbon chain fatty acids so can enter the Citric Acid Cycle
Food Sources of Vitamin B-12
• Synthesized by bacteria, fungi and algae• (Stored primarily in the liver)• Animal products• Organ meat• Seafood• Eggs• Hot dogs• Milk
Absorption of Vitamin B-12 (Fig. 10-10)
Therapy for Ineffective Absorption
• Many factors can disrupt this process
• Monthly injections of vitamin B-12
• Vitamin B-12 nasal gel
• Megadoses of vitamin B-12 to allow for passive diffusion
Functions of Vitamin B-12
• Helps convert methylmalonyl CoA to succinyl CoA (citric acid cycle)
• RBC formation
• Nerve functions– Maintains myelin sheath
• Megalobalstic anemia
Vitamin B-12 and Homocysteine(Fig. 10-11)
RDA for Vitamin B-12
• 2.4 ug/ day for adults and elderly adults
• Average intake exceeds RDA
• B-12 stored in the liver
• Non-toxic
Who is at Risk For Deficiency?
• Vegans
• Breastfed infants of vegan moms
• Elderly
• Individuals with AIDS or HIV
Deficiency of Vitamin B-12• Pernicious anemia
– Never degeneration, weakness– Tingling/numbness in the extremities (parasthesia)– Paralysis and death– Looks like folate deficiency
• Usually due to decreased absorption ability• Achlorhydria especially in elderly• Injection of B-12 needed• Takes ~20 years on a deficient diet to see nerve
destruction
Vitamin C
• Ascorbic acid (reduced form), dehydroascorbic acid (oxidized form)
• Synthesized by most animals (not by human)• Absorbed by a specific energy dependant
transport system• Passive transport if intake is high• Decrease absorption with high intakes• Excess excreted
Food Sources of Vitamin C
• Citrus fruits• Potatoes• Green peppers• Cauliflower• Broccoli• Strawberries• Romaine lettuce• Spinach
• Easily lost through cooking
• Sensitive to heat• Sensitive to iron,
copper, oxygen
Functions of Vitamin C
• Reducing agent (antioxidant)• Iron absorption• Synthesis of carnitine, tryptophan to
serotonin, thyroxine, cortiscosteroids, aldosterone, cholesterol to bile acids
• Immune functions• Cancer prevention?• Collagen synthesis
Collagen Synthesis (Fig. 10-12)
Antioxidant
• Can donate and accept hydrogen atoms readily
• Water-soluble intracellular and extracellular antioxidant
• Must be constantly enzymatically regenerated
• Needs are higher for smokers
RDA for Vitamin C
• 90 mg/day for male adults• 75 mg/day for female adults• +35 mg/day for smokers• Average intake ~72 mg/day• Fairly nontoxic (at <1 gm)• Upper Level is 2 g/day• Warning to people with hemochromatosis, oxalate
kidney stones
Deficiency of Vitamin C• Scurvy
– Deficient for 20-40 days – Fatigue, pinpoint hemorrhages– Bleeding gums and joints. Hemorrhages– Associated with poverty
• Rebound scurvy– immediate halt to excess vitamin C supplements
• Who is at risk?– Infants, elderly men – Alcoholics, smokers