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The Water-Soluble Vitamins. B-vitamins and vitamin C. B Vitamins. Originally thought to be one vitamin Actually, there are eight (maybe more) of them Act primarily as coenzymes in metabolic pathways Important for ATP production!!! Important for MANY additional functions. B Vitamins.

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the water soluble vitamins

The Water-Soluble Vitamins

B-vitamins and vitamin C

b vitamins
B Vitamins
  • Originally thought to be one vitamin
  • Actually, there are eight (maybe more) of them
  • Act primarily as coenzymes in metabolic pathways
    • Important for ATP production!!!
  • Important for MANY additional functions
b vitamins3
B Vitamins
  • Dietary requirement is linked closely to metabolic rate (i.e., production)
  • Ruminant requirements met by rumen bacterial synthesis
  • Hindgut bacterial synthesis and absorption is insufficient to meet full requirements for a horse or most colonic fermenters
    • Caprophagy helps “recycle” and better utilize vitamins for cecal fermenters
b vitamins sources
B Vitamins - Sources
  • VARIETY of feedstuffs!
  • Plant sources
    • Found in fibrous portion of plants
    • Most cereals and grain products are enriched
  • Animal sources
    • Liver
    • Milk
    • Egg
    • Beef, pork and chicken
b vitamin deficiency
B Vitamin - Deficiency
  • LOTS of symptoms including fatigue
  • Specific diseases for each vitamin deficiency (e.g., beriberi, pellagra)
thiamin or thiamine
Thiamin (or Thiamine)
  • First vitamin to be discovered
    • Prevents beri-beri in humans
      • Anorexia, weakness, enlarged heart, edema
  • Thiamin pyrophosphate (TPP) is the active form of the vitamin (coenzyme) essential for carbohydrate and protein metabolism
    • Decarboxylation of ketoacids
    • Conversion of pyruvate to acetyl–CoA
    • Conversion of -ketoglutarate to succinate (TCA cycle)
  • Very heat labile – easily destroyed
factors affecting thiamin requirements
Factors Affecting Thiamin Requirements
  • Carbohydrate intake
  • Thiaminase intake
    • Raw fish
    • Bracken fern poisoning in ruminants and horses
      • muscle tremor, incoordination, frequent falling, bradycardia and cardiac irregularity
  • Excess sulfur in ruminant diets(decreases thiamin synthesis)
thiamin b 1 deficiency
Thiamin (B1) - Deficiency
  • Polyneuritis – retraction of head in chicks
  • In ruminants, polioencephalomalacia or “stargazing” (head retracted)
  • Cardiovascular disturbances
    • Beriberi – heart enlargement, numbness
    • Bradycardia – slow heart rate
  • Severe thiamin deficiency in alcohol abusers: Wernicke-Korsakoff syndrome
    • Disorientation
    • Loss of short term memory
    • Jerky eye movements
    • Staggering gait

The limbic system (hippocampus, amygdale), parts of the diencephalons (mammillary bodies of the hypothalamus and dorsomedial nucleus within the thalamus), and parts of the basal forebrain (nucleus basalis of Meynert) all involved


Thiamin deficient chick on the right. Growth has been reduced due to interruption of the glycolytic pathway by lack of the coenzyme thiamin diphosphate.


Thiamin Deficiency - Polyneuritis

Thiamin-deficient rat shows typical arched back and hyperextended hind legs

Same rat 8 hours after receiving thiamin hydrochloride has normal use of its hind legs and normal vestibular reaction


Thiamine Deficiency Peripheral Neuritis

“Foot Drop”

(A) Peripheral neuritis of nutritional origin shows limit of flexion of ankles

(B) Moderate flexion is possible after 2 wk thiamine therapy




Thiamin Deficiency - Pitting Edema

(A) Swelling of legs with pitting in ankle region marks beginning of so-called wet beriberi

(B) 4 days after a single i.v. injection of thiamin




Thiamine Deficiency -

Beriberi Heart

A) Chronic alcoholic with extensive poor diet

B) After 1 wk thiamine therapy

C) After 3 wk treatment, reduction in heart size

riboflavin b 2 sources
Riboflavin (B2) - Sources
  • Milk and milk products
  • Enriched products
  • Liver
  • Ribo: ribose Flavin: yellow
  • Component of flavoproteins
  • Component of the coenzymesflavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)
    • FMN  FMNH2
    • FADH  FADH2
    • Coenzymes for a wide variety of enzymes of intermediary metabolism
    • FADH is a hydrogen carrier in glycolysis, TCA and oxidative phosphorylation (electron transport chain)
  • Absorbed by small intestine via active transport
  • Stable when heated
  • Breaks down in light and radiation
    • Milk sold in opaque/translucent containers
riboflavin deficiency
Riboflavin - Deficiency
  • Reduced growth
  • Ectodermal lesions
  • Curled-toe paralysis in birds
    • Due to nerve degeneration
  • Cataracts (swine)
    • Moon blindness in horses
  • Joint stiffness in swine
  • Ariboflavinosis
    • Inflammation of the mouth, skin, eyes, and GI tract

Riboflavin Deficiency

(A) Generalized dermatitis & growth failure

(B) After 1 month riboflavin treatment

(C) After 2 months treatment

niacin sources
Niacin - Sources
  • Milk; eggs, meat, poultry, fish,
  • Whole grains and enriched products
  • All protein containing foods
  • Occurs as nicotinic acid and nicotinamide
    • Body transforms nicotinic acid to nicotinamide, a major chemical form of niacin in the blood
  • Most mammals (except cats) can synthesize niacin from its precursor, tryptophan
    • Supplementation needed by all animals
niacin functions
Niacin - Functions
  • NAD and NADP are the main dietary forms of niacin
    • Heat-stable
  • Both are hydrolyzed by enzymes in the small intestinal mucosa to yield nicotinamide
  • Niacin can be synthesized from tryptophan
    • This process is not very efficient (60:1 tryptophan:niacin)
  • Niacin is essential for the formation of NAD and NADP (important in redox reactions) – THESE ARE THE ACTIVE FORMS OF THE VITAMIN
    • Nicotinamide adenine dinucleotide (NAD) acts as an electron acceptor in many biological redox reactions
      • NAD is a hydrogen carrier in glycolysis, TCA and oxidative phosphorylation (electron transport chain)
      • NADPH is a hydrogen donor in the synthesis of fatty acids
niacin deficiency
Niacin - Deficiency
  • Niacin in grain not available to monogastrics
  • Deficiency
    • Reduced growth and appetite
    • Black tongue – dog
    • Pellagra – farm animals and humans in “poor” areas of the world
      • Fiery inflammation of tongue, mouth and upper esophagus
      • Diarrhea, dermatitis, dementia, and death (the 4 D’s)
        • “Redneck” disease in niacin-deficient areas of the US
        • Major components of diet were the 3 M’s – meat (mostly pork fatback), molasses, and meal (corn meal)
        • Confusion, depression, poor memory
discovering the cause of pellagra
Discovering the Cause of Pellagra
  • High numbers of patients in insane asylums in the Southeast US in the first two decades of the 20th century suffered from pellagra – incidence rate reached epidemic proportions (3 million cases in the US alone)
    • Pellagra thought to be caused by contaminated corn or some infectious agent
  • Mississippi convict study (in exchange for a full pardon)
    • In 1915 Goldberger and 12 convict volunteers in Mississippi lived on a high-carbohydrate, high-fat, no-protein diet
    • All of the volunteers contracted pellagra
    • All were subsequently cured when their diets were changed
    • These findings were rejected by many scientists
  • Goldberger’s “filth parties” of 1916 (“Fifteen Men and a Housewife”)
    • Goldberger, several other “volunteers” (including his assistants), and his wife undertook the following procedures:
      • injecting the fresh blood of people sick with pellagra into their own bodies
      • swallowing vials bearing "little dough balls” impregnated with the urine and feces of sufferers
      • swallowing vials of dough balls combined with the scaled-off skin of the afflicted (cheek scrapings)

None of those exposed contracted pellagra!


Early Pellagra - Glossitis

Dental indentations resulting from edema - lip & tongue margins scarlet


Advanced Pellagra

Dermatitis of elbows due to friction - beginning of desquamation in the center of lesion


Pellagra - Casal’s Collar or Necklace

Photosensitive dermatitis outlining exposed area of neck & lesions on back of hands - sunlight or heat from a stove can induce this reaction

Same patient after nicotinamide therapy

pantothenic acid
Pantothenic Acid
  • Food sources:
    • Organ meats
    • Whole grains
    • Legumes
  • Unstable in heat
    • Destroyed by food processing
pantothenic acid absorption
Pantothenic Acid - Absorption
  • Coenzyme A (CoA) is the biologically active form of pantothenic acid
  • CoA from dietary sources is hydrolyzed in the intestinal lumen to pantothenic acid which is absorbed into the bloodstream by a Na+-dependent transporter
pantothenic acid functions
Pantothenic Acid - Functions
  • Part of co-enzyme A and acyl-carrier protein
    • Two-carbon carrier (ex., acetyl CoA)
    • Fatty-acid synthase complex
pantothenic acid functions33
Pantothenic Acid - Functions
  • Essential for the synthesis of fatty acids and membrane phospholipids, including sphingolipids
  • Essential for oxidation of fatty acids and amino acids
  • Essential for the synthesis of steroid hormones
  • Essential for the synthesis of hemoglobin
  • CoA contributes an essential acetyl group during the synthesis of the neurotransmitter acetylcholine and to several glycoproteins and glycolipids
pantothenic acid deficiency
Pantothenic Acid - Deficiency
  • Deficiency is rare; “the burning feet”
    • Goose stepping - swine
      • Cannot bend hock joint (nervous system degeneration)
  • Reduced growth, dermatitis, diarrhea

Pantothenic acid deficiency - Chick

Dermatitis in chick on pantothenic acid deficient diet

Three weeks after calcium pantothenate added to diet, skin lesions cured

pyridoxine b 6 sources
Pyridoxine (B6) - Sources
  • Meat, fish, poultry, liver
  • Non-citrus fruits
  • Legumes
vitamin b 6 pyridoxine
Vitamin B6, Pyridoxine
  • Pyridoxine, pyrodixamine,and pyridoxal
    • Active form is coenzyme pyridoxal phosphate (PLP)
    • Exists in plants as pyridoxine or pyridoxal
    • Exists in animals as pyridoxamine or pyridoxal
pyridoxine functions
Pyridoxine - Functions
  • Transamination processes
    • Create non-essential amino acids
  • Decarboxylation of amino acids
    • Energy from protein
  • Conversion of glycogen to glucose
    • Glycogen phosphorylase
  • Production of serotonin
  • Production of epinephrine and norepinephrine
vitamin b 6
Vitamin B6
  • Function
    • Coenzyme for reactions in protein and nitrogen metabolism
      • Pyridoxyl phosphate (PLP) in transaminases
    • Red blood cell formation
  • Deficiency
    • Nervous system degeneration
    • Reduced antibody response
    • Symptoms include depression, confusion

Spontaneous Seborrheic Dermatitis

Dermatitis around eyes, nose, mouth similar to that produced by pyridoxine antagonist

Same patient after 3 weeks of pyridoxine ointment therapy


Pyridoxine Deficiency

Edema & denuding of ears, paws & snout

After3 weeks of pyridoxine hydrochloride

cobalamin sources
Cobalamin - Sources
  • Animal sources: meat, fish, poultry, eggs, shellfish, milk/products
  • Plant sources: none
  • Microbes!!
vitamin b 12 cobalamin
Vitamin B12, Cobalamin
  • Not synthesized by plants
    • “Animal-protein factor”
    • Often deficient in monogastric diets
  • Microbes synthesize B12
    • Cobalt required
    • Some B12 synthesized in the hindgut
      • Not enough for most hind-gut fermenters, except horses
cyanocobalamin b 12
Cyanocobalamin (B12)
  • Active form is cyanide derivative of cobalamin - cyanocobalamin
  • Cobalt is an integral component
  • Close relationship between vitamin B12 and folate
    • Depend on each other for activation
cobalamin absorption
Cobalamin Absorption
  • HCl and pepsin in the stomach release B12 from protein foods
  • Requires intrinsic factor for absorption
    • Secreted by parietal cells
    • Only essential function of stomach
  • Intrinsic factor attaches to B12 and the whole complex passes to the small intestine where the gradual absorption of B12 occurs
vitamin b 12 functions
Vitamin B12 - Functions
  • Related to folic acid metabolism
  • Coenzyme for numerous reactions
    • Methylmalonyl CoA to succinyl CoA
    • DNA synthesis
    • Transmethylation (methionine synthesis)
cobalamin functions
Cobalamin - Functions
  • Vitamin B12 as a coenzyme is involved in the transfer of methyl groups to homocysteine to form methionine
  • It is also important for the

methylation of uracil to form

thymine which is converted

to thymidine and used for

DNA synthesis

cobalamin deficiency
Cobalamin - Deficiency
  • Deficiency often caused by inadequate absorption rather than poor intake
    • Lack of HCl or lack of intrinsic factor
      • Without HCl, the vitamin cannot be released from protein, and cannot attach to intrinsic factor
    • Atrophic gastritis:
      • Common in geriatric animals - stomach cells get damaged
        • Could also be due to iron deficiency or Helicobacter pylori
        • No healthy cells - decreased HCl and intrinsic factor
        • Result is pernicious anemia due to a combination of atrophic gastritis and lack of intrinsic factor
    • Other factors are defective gene for intrinsic factor, or if the stomach is injured or damaged
cobalamin deficiency49
Cobalamin - Deficiency
  • Reduced growth
  • Anemia
    • Pernicious anemia in humans (lack intrinsic factor)
      • Macrocytic anemia (large red blood cells)
      • Neural symptoms
    • Wasting disease in ruminants (Co deficiency)
cobalamin and folate
Cobalamin and Folate
  • High dose of folate masks B12 deficiency
    • In both deficiency states, the first symptom is that the blood cells grow rapidly
    • Either of the vitamins will be effective in resolving symptoms - however if folate is administered when B12 is needed, the situation will be disastrous
      • Results in devastating neurological symptoms
      • B12 deficiency leads to nerve damage caused by destruction of myelin sheaths that protect the nerves
      • Note: folate can clear the blood symptoms but cannot stop the nerve damage

Pernicious Anemia

Vitamin B12, Folic Acid, Ascorbic Acid Deficiency

Tongue pale & shiny; papillae atrophied in the course of the glossitis which is often the first symptom of the disease. The tongue may become red and sore; these symptoms usually subside promptly with appropriate nutritional therapy

folate sources
Folate - Sources
  • Animal sources
    • Liver
    • Crab meat
  • Plant sources
    • Green forage crops
    • Legumes
    • Seeds
  • Unstable; destroyed by heat and oxygen
  • Caution with feed processing, preparation and storage
folic acid
Folic Acid
  • Folates are a family of compounds that have pteroylglutamate as a common structure
    • Tetrahydrafolic acid is active functional form
  • Donor and acceptor of one-carbon (e.g., methyl) groups
folate folic acid
Folate (Folic Acid)
  • Involved in protein metabolism
  • Critical role in the synthesis of DNA
    • Involved in new cell development
    • Requires the help of the vitamin B12
  • Folate is secreted into the GI tract with bile
    • If the cells of the GI tract are injured/destroyed as in the case of alcohol abuse, then folate can not be absorbed, and leads to deficiency
folate deficiency
Folate - Deficiency
  • Macrocytic or megaloblastic anemia, and GI tract deterioration
    • Diarrhea, fatigue, depression and confusion
    • Impairs cell division and protein synthesis
      • Reduced growth
    • Alters DNA metabolism
  • Folate deficiency masks vitamin B12 deficiency
  • Folate status affected by drugs with similar chemical structure
    • Can lead to secondary deficiency
    • Many anti-cancer drugs can create deficiency of folate to other normal cells
    • Antacids and aspirins interfere with folate
    • Smoking and oral contraceptives affect folate status
folate deficiency56
Folate - Deficiency
  • Pregnant women prone to deficiency
    • Studies have documented the need for folate to reduce the risks of neural tube defects
    • Spina bifida in humans
      • Folate deficiency in early pregnancy, especially around 3 weeks after conception

Folic Acid Deficiency - Chick

Supplemented with 100 mg/kg folic acid - normal growth rate, feathering, and blood values

Deficient chick is stunted, poorly feathered and severely anemic

biotin sources
Biotin - Sources
  • Animal sources - organ meats, egg yolks, fish
  • Plant sources - soybeans, whole grains
  • Stable to heat
  • Involved in carboxylationsand decarboxylations
    • Coenzyme involving CO2 transfer
    • Lipid metabolism
      • Fatty acid biosynthesis
        • propionyl CoA to methylmalonyl CoA
        • acetyl CoA to malonyl CoA
    • Carbohydrate metabolism
      • Pyruvate to oxaloacetate (TCA cycle)
biotin deficiency
Biotin - Deficiency
  • Avidin binds biotin
    • Found in raw egg white
    • Bond broken by heating to 100°C
  • Deficiency symptoms
    • Cracked nails, hooves, dermatitis, hair loss
    • Dermatitis
    • Perosis
  • Fatty liver and kidney syndrome, a fatal metabolic disorder in chicks and turkey poults

Biotin Deficiency – Rat

Same rat 3 weeks after biotin was added to diet

Generalized alopecia

Normal rat

  • Food sources;
    • Milk, liver, eggs and legumes
  • Synthesized in body
    • Methionine can be converted to choline in liver
choline functions
Choline - Functions
  • Source of CH3 groups (methyl donor)
    • After conversion to betaine
  • Precursor of acetylcholine (neurotransmitter)
  • Component of phospholipids
  • Phosphatidyl choline (lecithin)
    • Emulsifier
  • Chylomicron formation
choline deficiency
Choline - Deficiency
  • Deficiency may cause liver damage
  • Fatty liver; kidney degeneration
  • Perosis – chicks
    • Slipped tendon
    • Malformation of leg bone

Choline Deficiency - Human

Treated with moderate fat diet plus choline

Fatty infiltration of liver

non essential nutrients
Non-Essential Nutrients
  • Inositol and carnitine
    • Synthesized in the body from glucose and amino acids respectively
  • Inositol used in cell membranes
  • Carnitine used for beta-oxidation of fats
ascorbate sources
Ascorbate - Sources
  • Vitamin C is also known as ascorbic acid, ascorbate
  • Found in citrus fruits, cabbage type of vegetables, green leafy vegetables, cantaloupe, strawberries, lettuce, tomatoes, potatoes, papaya and mango
  • Destroyed by exposure to oxygen
  • Destroyed by heat
vitamin c
Vitamin C
  • Most mammals synthesize ascorbate from glucose including farm animals
    • Primates and guinea pigs require a dietary source of vitamin C
      • Humans and other primates lack the terminal enzyme, gulonolactone oxidase, in the ascorbate biosynthetic pathway
        • The gene is present, but the coding sequence has so many mutations that there is no product
vitamin c ascorbic acid
Vitamin C (Ascorbic Acid)
  • Antioxidant
    • Protects cells from free radicals
    • Protects iron from oxidative damage, thus enhancing iron absorption in the gut
  • Assists as co-factor in collagen formation
    • Collagen is the main structural protein in bones, teeth, cartilage, tendons, ligaments, skin and blood vessels
  • Helps in the hydroxylation of carnitine
  • Conversion of tryptophan to neurotransmitters serotonin and norepinephrine
  • Enhances iron absorption and regulates the absorption of copper
other potential functions
Other Potential Functions
  • Reduce stress (e.g., infections, smoking)
    • Mechanism unknown, but vitamin C requirements increase during stress
  • Common cold? Disease prevention?
    • Cancer, heart disease: inconclusive…
vitamin c deficiency
Vitamin C - Deficiency
  • Scurvy in humans
    • Not in farm animals
    • Structural defects of bone, connective tissue
    • Bleeding gums; pinpoint hemorrhage
    • Fatigue; microcytic anemia
    • Loss of appetite
    • Slow wound healing; frequent infections
    • Scaly and dry skin; neurological symptoms
    • Edema
    • Loose teeth, gum problems
    • Diarrhea
vitamin c discovery
Vitamin C - Discovery
  • Prior to discovery, sailors on long-term voyages commonly used to die from scurvy
  • In 1930’s James Lind found that citrus fruits (limes used first) prevented scurvy by experimenting on British sailors
  • Why Brits are called “limeys”

Vitamin C – Scurvy in Human Scorbutic Rosary

X-ray of a child with scurvy

Enlarged costochondral junctions of scurvy resembles rickets - lesions may feel sharper & may be tender


Vitamin C – Scurvy in Human

Child in scorbutic position. Because movement is painful, infant usually lies on its back, makes little attempt to lift leg or arm – hurts. Legs may be tender and sometimes both arms as well. Usually first sign of scurvy.


Bone Lesions - Scurvy

Fracture at lower end of tibia

Fractures between epiphysis and shafts of femur, tibia and fibula


Vitamin C – Scurvy in Human


Capillary fragility after application of a blood pressure cuff

ascorbate toxicity
Ascorbate Toxicity
  • Nausea, abdominal cramps and diarrhea
  • Interference with medical diagnostic tests
    • False positive or false negative to detect diabetes
    • Individuals taking anti-clotting medication may counteract the effect if they take high doses of vitamin C
    • Dangerous for people with iron overload
rebound scurvy
Rebound Scurvy
  • When high doses of vitamin C are taken, body excretes it rapidly
    • When abruptly stopped, the body is unable to immediately reduce rapid excretion rate
    • Potentially results in vitamin C deficiency