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+ Citric Acid
Alpha-ketogluterate Succinyl CoA Cycle
NAD+ NADH + H+
Malate Oxaloacetate

• Electron transport chain

 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
(Fig. 10-8)
• Spina bifida
• Anencephaly
• Importance of folate
before and during
pregnancy
 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 • Easily lost through
• Potatoes cooking
• Green peppers • Sensitive to heat
• Cauliflower • Sensitive to iron,
• Broccoli copper, oxygen
• Strawberries
• Romaine lettuce
• Spinach
 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