BIOCHEMISTRY
VITAMINS(WATER SOLUBLE)
STRUCTURE FUNCTION,CLASSIFICATION,CLINICAL
IMPORTANCE
LEARNING OBJECTIVE.
• At the end of lecture student should be able to know,
• Overview of water solube vitamins.
• Thiamine, sources,structure,function.
• Ribofalvin sources,structure,function.
• niacin sources,structure,function.
• Vitamin B_6 sources,structure,function.
• Folate sources,structure,function.
• Vitamin B_12 sources,structure,function.
• Pantothenic acid sources,structure,function.
• Biotin sources,structure,function.
• Vitamin C sources,structure,function.
• OVERVIEW OF WATER-SOLUBLE VITAMINS
• Dissolve in water
• Generally readily excreted
• Subject to cooking losses
• Function as a coenzyme
• Participate in energy metabolism
• Susceptible to heat
• Kidney removes and excretes excess
• Vitamin C, thiamin and riboflavin are especially
susceptible to heat and alkilinity
• Hydrophilic and water will leach them from
vegetables
• Marginal deficiency more common
• WATER SOLUBLE VITAMINS
Thiamin Pantothenic Acid
Riboflavin Biotin
Niacin Vitamin C
Vitamin B-6
Folate
Vitamin B-12
• THIAMIN
• Sulfur containing and nitrogen containing rings
attached to carbon atoms
• Part of nerve cell membranes—synthesize and
regulate neurotransmitters
• Functions in energy metabolism—vitamin portion of
TPP; plays role in decarboxylation and helps form
Acetyl Co A from pyruvate
• DEFICIENCY
• Heavy alcohol consumption with inadequate food
consumption ; alcohol interferes with absorption
(Wernicke-Korsakoff syndrome); poor and elderly at
risk for not eating sufficient energy
• 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
• CHEMICAL CHARACTERISTICS
• Very labile nutrient
• Heat
– stable in crystalline form
– less stable in solution
• Alkali - very unstable with heat
– baking soda
• Sulfites - decomposes B-1
• High cooking/processing losses
– heat
– leaching
• 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
• Enriched grains
• Liver
• Oyster
• Brewer’s yeast
• Sensitive to uv radiation
(sunlight)
• Stored in paper, opaque
plastic containers
• Most plant and animal foods
• Milk and milk drinks and yogurt supply about 15% in
the American diet
• Fortified cereals, bread and bread products contribute
about 10%
• One of four vitamins added to enriched products
• 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
• DEFICIENCY/TOXICITY
• Deficiencies are rare although some people may take
in marginal amounts
• Drug and alcohol users and restricted caloric intake
• Ariboflavinosis
• Toxicity– not observed
• 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
• 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
• NIACIN (NICOTINIC ACID)
• Made from tryptophan; essential nutrient if protein
intake is inadequate
• 60 mg tryptophan converts to 1 mg niacin
• RDA is 14-16 NE/day for adults
• NE include preformed and niacin derived from
tryptophan
• 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
• DEFICIENCY OF NIACIN
• Pellagra
– Occurs in 50-60 days
– Decrease appetite & weight
• Prevented with an adequate protein diet
– (Untreated) corn as main staple, poor diet, Hartnup
disease, alcoholics are at risk.
–
• 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
• 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
• 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
• 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
• Neural Tube Defects
• 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
• 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
• 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
• PANTOTHENIC ACID
• Part of Coenzyme-A
• Essential for metabolism of CHO, fat, protein
Glucose
Fatty acids Acetyl-CoA Amino Acids
Alcohol
• PANTOTHENIC ACID SOURCES
• Widespread in
foods
• Organ meats
• Mushrooms
• Avacado
• Broccoli
• Whole grains
• 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
• BIOTIN SOURCES
• Widespread in foods
• Organ meats, fish
• Egg yolks
• Soybeans
• Whole grains
• 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
• 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 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
• VITAMIN C - ASCORBIC ACID
• Structure
• Metabolism
– oxidation/reduction
– dehydroascorbic acid
– dehydroascorbate reductase
– glutathione (GSH)
• glutamate-cysteine-glycine
• FUNCTIONS OF VITAMIN C
• Antioxidant—donates electron minimizing free radical
damage; Recycles oxidized vitamin E for reuse
• Collagen synthesis
• Stabilizes reduced form of folate enzyme
• Enhances absorption of non-heme iron
• Helps synthesize carnitine
• Proper functioning of immune system
• VITAMIN C DEFICIENCY/TOXICITY
• Scurvy
• Breakdown gums and joints
• Bone pain, diarrhea, fractures, fatigue
• UL is 2,000 mg per day
• Can possibly enhance oxidation when consumed in
high doses without other antioxidants
• COLLAGEN SYNTHESIS
•
• REFERENCES
• Internet.
• Essentials of medical biochemistry(Mushtaq ahmad6th
edition)