Vitamins

Definition
Organic compounds for maintenance of normal metabolic integrity
Vitamin D and Niacin are not vitamins
oVitamin D- hormone
oNiacin- compound

FAT SOLUBLE VITAMINS

Absorption dependent on ileum, bile, and pancreas
Toxicity more common
Affected by malabsorption syndromes
VITAMIN

FORMS
Retinol

Vitamin A Alcohol

Supports gametogenesis in gonads

Sugar Transport
When oxidized to retinoic acid, binds
to nuclear receptors

Vitamin A Aldehyde

Vision (present in rod and cone cells

Functions as prosthetic group of
opsins forming Rhodopsin and
Iodopsin

Vitamin A Acid
(All trans-retinoic A, 9cis-retinoic A)

Coenzyme
VITAMIN A
Vitamin most stored in the
liver (inside Ito cells)
Provitamin:
Beta-carotene
o Vegetables
o Fruit
Retinol
o Milk
o Liver
o Egg Yolk

Retinal
Visual pigment

Retinoic Acid
Signal molecule

Retinyl esters
Retinol-Binding
Protein (RBP)

FUNCTIONS

Storage form (in liver

and adipose tissues)
Transport form

Development differentiation
Growth regulators in epithelium
Tretinoin- all-trans retinoic acid
Isotretinoin- 13-cis-retinoic acid
Both Tretinoin and Isotretinoin are
teratogenic
Storage form (in liver and adipose
tissues)
Transport form

SYNTHESI
S

TRANSPORT
Dietary retinol is transported as retinyl
esters in chylomicrons
Retinol is secreted by the liver in
association with plasma retinol-binding
proteins

SOURCES
Retinyl esters and
retinol- animal tissues
Beta-carotene- found
in certain plants

CLINICAL CORRELATES/ PATHOLOGIES

ASSOCIATED
DEFICIENCY
Loss of sensitivity to green light
o Nyctalopia- night blindness; earliest
manifestation
o Xerophthalmia- corneal keratinization
and ulceration; (+) Bitots spots
Increase infections
Impotence
Growth retardation
EXCESS (HYPERVITAMINOSIS A)
Pseudotumor cerebri- ICP
o Benign intracranial hypertension
Excessive dryness, desquamation,
alopecia
Hepatomegaly
Increase fractures
Teratogenic
o Craniofacial malformation, Neural
Tube Defects

FORMS

VITAMIN

Ergocalciferol (Vit
D2)
Cholecalciferol (Vit
D3)
Calcitriol
7dehydrocholesterol
25-(OH) vitamin D3

FUNCTIONS
Milk, plant
sources
Skin, animal
sources
1,23(OH)2vitamin
D3

Intestine

Storage
Responds to
hypocalcemia and PTH
oIncreased intestinal
absorption of Ca
oIncrease bone
deposition/
resorption
oIncrease kidney
reabsorption

Most toxic vitamin

Active Form

PTH VS. ACTIVE VITAMIN D METABOLITES

Organ

Precursor

VITAMIN D
(CALCIFEROL)

1,25-(OH)2 vitamin
D3

SYNTHESIS

SKIN, UV light
7-dehydrocholesterol

Cholecalciferol (Vit D3)

LIVER, 25- hydroxylase

25-hydroxycholecalciferol
KIDNEY, -1 hydroxylase

1,25-DHCC (Calcitriol)

Kidney

Bone: Mineralization or
Mobilization (with PTH)
Intestine: Increase calcium
intake

Bone

Net Effect on
Serum Levels

VITAMIN

FORMS
Phylloquinone
Menaquinone
Menandione

Vitamin K1
Vitamin K2
Synthetic

FUNCTIONS
Carboxylation of glutamic acid residues in many Ca binding proteins
Activation of Coagulation Factors I,IX,VII,II (Vit K Dependent, Extrinsic)
Protein C and S

VITAMIN K

PTH

Active Vitamin D Metabolites

No direct effect
Increase Ca and Phosphate
absorption by VIt D. Metabolites
Released in response to
hypocalcemia
Increased calcium and
decreased phosphate
Ca reabsorption (DT),
decreased Phosphate
Reabsorption (PCT)
OR
Ca excretion (DT), increased
Phosphate reabsorption (PCT)

Ca and Phosphate resportion

increased by continuous high
concentration

INC Ca, DEC Phosphate

SYNTHESIS

TRANSPORT

Increase calcium and phosphate

absorption

Increased reabsorption of Ca and

phosphate but usually net increase
in urinary Ca

CLINICAL CORRELATES/
PATHOLOGIES ASSOCIATED
DEFICIENCY
Rickets
o Present in children
o Pigeon chest deformity, bow
legs
Osteomalacia
o Present in adults
o After closing of growth plate
EXCESS (HYPERVITAMINOSIS
D)
Hypercalcemia
May also cause:
o Cardiac arrest
o Anorexia and nausea
o Thirst
o Stupor
o Keratogenesis in babies
(malformation)

DIRECT
Increased calcium and phosphate
resorption
INDIRECT
Promote mineralization by inc
availability of Ca and Phosphate
INC Ca and Phosphate

SOURCES
Green vegetables
Intestinal bacteria

CLINICAL CORRELATES/ PATHOLOGIES ASSOCIATED

DEFICIENCY
RARE (produced by bacterial GIT)
Hemorrhagic Disease of the Newborn
o Presents as bleeding
o Sterile GIT and low Vit K Content of breast milk
EXCESS
Jaundice + Hemolytic Anemia

VITAMIN E (-TOCOPHEROL)
Least toxic vitamin

Work against oxygen free radicals or ROS

Protects membrane lipids from peroxidation
Prevent oxidation of LDL
o Decrease atherogenesis

Antidote for Warfarin Overdose

DEFICIENCY
Dietary deficiency among humans unknown
o RBC fragility hemolytic anemia
o Neurologic dysfunction (neuropathy)
o Muscle membrane damage

WATER SOLUBLE VITAMINS

Generally non-toxic since excesses just wash out of the body in urine
EXCEPTIONS: B3, B6, B12
REVIEW
o
Cofactor- transient
o
Coenzyme- substrate shuttle
o
Prosthetic groups- tight and stable attachment to enzyme
VITAMIN

FORMS

FUNCTIONS

VITAMIN B1 (THIAMINE)

Thiamine Pyrophosphate (active form)

Cofactor in:
Pyruvate dehydrogenase, -ketoglutarate
dehydrogenase, and branched chain AA dehydrogenase
Transketolate reactions in HMP

VITAMIN B2 (RIBOFLAVIN)

Flavin Mononucleotide (FMN)

Flavin adenine dinucleotide (FAD)

Cofactors in redox reactions, as electron carrier

Food additive due to intense yellow color

NAD+P

Coenzyme in redox reactions

Source of ADP ribose for proteins and nucleoprotein in
DNA repari

VITAMIN B5 (PANTOTHENIC ACID)

Active form: constituent of Coenzyme A

Cofactor for acyl transfers

Component of FA synthase

VITAMIN B6 (PYRIDOXINE)

Pyridoxal phosphate

Coenzyme for AA transamination

Coenzyme for glycogen phosphorylase, cystathione
synthase, ALA synthase
Removes hormone-receptor complex from DNA- stops
steroid hormone action
Synthesis of niacin from tryptophan

VITAMIN B12 (COBALAMIN)

Methylcobalamin-

Structure: cobalt in the center of Corrin

Ring

Cyanocobalamin
5deoxyadenosylcobalamin
Methylcobalamin

VITAMIN B3 (NIACIN)
Not a true vitamin
May be derives from tryptophan
using B6

Needs Intrinsic Factor for absorption

contains
methyl group
Contains CN
Active form
Active form

SOURCES

Milk
Destroyed when
exposed to sunlight

Found in majority of
food

Animal source
Methionine Synthesis
Homocysteine N-methyl-THF methionine + THF
Isomerization reactions

CLINICAL CORRELATES/ PATHOLOGIES ASSOCIATED

DEFICIENCY
Wet Beri-Beri
o Wet- with heart failure
o Dilated cardiomyopathy (high output cardiac
failure)
o edema
Dry- Beri-Beri
o Dry- no heart failure
o Polyneuritis
o Symmetrical muscle wasting
Wernicke-Korsakoff Syndrome
o Wernicke Ecepahalopathy- Ataxia, Confusion,
Ophthalmoplegia
o Korsakoff Psychosis- confabulation,
hallucination, amnesia
No deficiency state but with signs of
o Stomatitis
o Cheilosis
o Seborrheic dermatitis
o Corneal vascularization
Pellagra
o Diarrhea, Dermatitis, Dementia, Death
Hartnup disease- decreased tryptophan absorption
Carcinoid syndrome- increased tryptophan
metabolism
Isoniazid use- decrease vit B6
No deficiency state but with signs of
Dermatitis
Enteritis
Alopecia
Adrenal insufficiency
Isoniazid toxicity
o INH + pyridoxal phosphate= inactive derivative
o Peripheral neuropathy

Pernicious Anemia
Autoimmune destruction of parietal cells dec IF
secretion dec B12 absorption
Early: megaloblastic anemia
Late: neuropsychiatric

EXCESS

Liver Damage

>200 mg/day
gait problems and
CNS toxicity

VITAMIN

FORMS

FUNCTIONS

SOURCES

Methymalonyl CoA succinyl CoA (enzyme: methylmalonyl

mutase)
VITAMIN B9 (FOLIC ACID)
Most common vitamin deficiency in
developed countries
Structure: pterin ring+PABA_gultamate
residues

VITAMIN B7 (BIOTIN)

VITAMIN C (ASCORBIC ACID)

PABA

Dihydrofolate

Tetrahydrofolate

Coenzyme for 1-C transfer

o Methylation reactions, like synthesis of purines and
thymine

Enzymes for conversion

Dihydropteroate synthetase (PABA DHF)
Dihydrofolate reductase (DHF THF)

Cofactor for carboxylation reactions

Pyruvate carboxylase
o Pyruvate oxaloacetate
Acetyl CoA Carboxylase
o Acetyl CoA malonyl CoA
Propionlyl CoA carboxylase
o Propionyl CoA methylmalonyl CoA
COFACTOR IN
Hydroxylation of proline and lysine (Collagen Synthesis)
Dopamine-B- hydroxylase (dopamine to norepinephrine)
Reduces Fe3+ to Fe2+ in stomach to increase Fe
absorption

Leafy vegetables

CLINICAL CORRELATES/ PATHOLOGIES ASSOCIATED

DEFICIENCY

EXCESS

Test: Schilling Test, Vit B12, and anti-IF

Other causes: malabsorption or absence of terminal
ileum
Megaloblastic anemia with no neurologic symptoms
o Earliest manifestation: hypersegmented
neutrophils
Functional folate deficiency in those with increase
homocysteine increased risk of MI
Neural tube defects
o Pregnant mothers: 400mcg folate/day
CLINICAL CORRELATES
Methotrexate- anticancer drug
o Inhibits DHF in humans
Co- Trimoxazole
o Anti-metabolite, inhibits both processes in THF synthesis of bacteria
o Trimethoprin- DHF reductase
o Sulfomethoxazole- Dihydropteroate synthase
Induced by avidin in egg whites
Dermatitis
Enteritis

Scurvy
Most important symptom: bleeding gums, hair
follicles due to lack of collagen
Loose teeth and sore gums
Swollen joints
Fragile vessels
Anemia