VITAMINS

Vitamins are low molecular organic compounds, indispensable for the normal vital
activity of the organisms

Properties of vitamins:
1. Synthesized outside the human body.
2. Highly active in small doses.
3. They are not plastic and energetic material.
4. Insufficiency leads to the formation of specific pathological conditions: hypo- or
avitaminosis.
5. When used in higher doses, hypervitaminosis is formed.

The vitamin compounds are classified in:

 Vitamins
 Vitaminoids – similar as function but required in larger amounts

The same compound may be a vitamin for some organisms and an ordinary
substance for others (ascorbic acid is a vitamin for human and guinea-pigs since it is
not synthesized in their organism and not in rat, rabbit, dog)
Functions:
 Take part in the production of coenzymes
 Indispensible for the activity of the coenzymes
 Regulators of biochemical processes
CLASSIFICATION of VITAMINS
VITAMIN SOURCE
Source:
 Food intake
 Synthesis in the intestin - bacteria
In the organism, the vitamins may exist as
 active vitamins or
 provitamins which need a transformation in the organism in order to become
active; for example:
 Carotenes are provitamins of vitamin A; they are oxidized in the intestinal
mucosa, with the participation of carotene dehydrogenase, to generate
vitamin A
 Derivatives of sterols are provitamins of vitamin D:
 ergosterol  ergocalciferol (vit D2);
 cholesterol  7-dehydrocholesterol  cholecalciferol (vit D3)
The vitamins and provitamins are transported to different organs and tissues where
they perform their biochemical and physiological function
They may be accumulated in different organs
VITAMIN BALANCE
DEFICIENCY (negative balance)
Partial deficiency = hypovitaminosis
 1 vitamin deficiency = monohypovitaminosis
 More vitamins deficiency = polyhypovitaminosis
Extreme deficiency = avitaminosis
Hypovitaminosis manifest in a retarded growth of the young organisms, with
specific intrinsic symptoms for each vitamin deficiency.
Causes:
 Exogeneous factors:
 Unbalanced diet
 Dysbacterioses after antibiotics, chemotherapeutic agents
 Endogeneous factors:
 Disorder in the absorbtion or transport of the vitamin, formation of the
coenzyme (genetic defects of the synthesis of the apoenzyme or enzyme)
  Increased vitamin catabolism
 High requirements (pregnancy, growing organisms)

EXCESS (positive balance) = hypervitaminosis

Symptoms
 Loss of apetite
 Headache
 Disorders of the gastrointestinal tract
 High excitability of the nervous system
 Hair loss
 Skin desquamation
May lead to fatal outcome
Causes:
 Excessive intake of food rich ina fat-soluble vitamin (liver of whale and polar
bear rich in vit A)
 Prescription of high doses of vitamin

ANTIVITAMINS
Are structural analogues: their structure looks like the structure of vitamin
They act as antagonists, inhibiting or blocking the activity of the vitamin as
coenzyme, thus the physiological processes are disturbed
They produce symptoms as the vitamin deficiency does
Examples:
 Antibiotics
 Sulfonamides
 Enzymes( ascorbase acts on ascorbic acid, tiaminase on thiamine,
lipoxygenase oxidize the provitamin A)

Types of action of vitamins:

1. Specific - associated with their effect on metabolism;
2. Nonspecific - not due to a typical metabolic effect (for example: PP - dilates blood
vessels, reduces the activity of the blood coagulation system, hypolipidemic effect).
Types of vitamin therapy:
1. Adaptation - used in the absence of hypovitaminosis, but in the presence of
conditions that may lead to this:
a) use doses of drugs close to the daily requirement;
b) Apply multivitamin preparations;
c) Treat with courses of at least 3 weeks;
2. Pharmacodynamic therapy:
a) use 1 drug;
b) doses 10-100 times higher than daily;
c) treatment continues depending on the patient's condition.

WATER SOLUBLE VITAMINS

Complex B - General features
1. soluble in water
2. coenzymes in biochemical processes of great importance
3. activators - stimulate metabolic processes and regulate them
4. growth factors for microorganisms and young organisms
5. the most of them are synthesized by intestinal microflora (thiamine,
pantothenic acid, nicotinamide, pyridoxine, folacine, corinoids, PABA)
Complex C: ascorbic acid, flavonoids (C2)

THIAMINE, VITAMIN B1
Source: plants (coarse bread, pea, beans) and meat products
Active form: thiamine diphosphate (T-PP)
Daily requirement: 1-3 mg
NH2
H2 CH3
NH 2 C O O
H2 CH 3 N N+
C
N N+ H3C N NH2 S
CH2 CH2 O P O P OH
OH OH
CH 2 CH2 OH
H3C N NH2 S
Structure: T-PP

Metabolism: dietary thiamine is hydrolyzed to free thiamine, which is absorbed in the

intestine by diffusion; transported through the portal vein to the liver where is
phosphorylated to thiamine-diphosphate (TDP, T-PP) or thiamine triphosphate
(TTP); a part of the free thiamine is transported to tissues where it is
phosphorylated.
In the cells T-PP is bound to the enzyme or stored in the muscles, intestine, liver.
When the coenzyme is broken down, the free thiamine is released, passes in the
blood and is excreted in urine.
In tissues, TTP is formed from T-PP and ATP; it is involved in the neuron conduction
and transmission of the nervous impulse

Biochemical functions:
TPP facilitates the mitochondrial oxydation of pyruvate and 2-oxiglutarate (energy
generation from carbohydrates and aminoacids)
Essential in all processes that use NADPH+H+:
 synthesis of fatty acids and sterols,
 synthesis of nucleotides, nucleic acids, nucleotide coenzymes,
 detoxification of drugs and toxins.
Defficiency = BERI-BERI: metabolism disturbances (catabolic processes are
prevalent) and impaired functions of digestive, cardiovascular and nervous system:
loss of appetite, reduced secretion of gastric juice, diarrhea;
reduced contractility of muscles, myocardium, smooth muscles
decrease of peripheral sensibility, reflexes, neuralgia, impaired higher nervous
activity
Frequent in chronic alcohol addicts
Practical application: help the carbohydrates assimilation in diabetes mellitus,
hypovitaminoses, dystrophy of heart,and skeletal muscles, inflammation of the
peripheral nerves

RIBOFLAVIN, VITAMIN B2
Source: liver, kidney, eggyolk, cheese and intestinal microflora
Daily requirements: 1-3 mg
CH2 (CHOH)3 CH2 OH
N N
H3C C O
H3C NH
N C

Structure O
Metabolism:
 in food is present as FMN, FAD bound to protein or free in microorganisms;
 in the intestine it is released and absorbed by simple diffusion;
 used to synthesize FMN and FAD and flavin coenzymes
 flavoproteins are catabolyzed to free riboflavin, excreted in urine.

PANTOTHENIC ACID, VITAMIN B3

Source: yeast, eggs, milk, meat, liver, fish, vegetables and intestinal flora
Requirements: 10 g/day
CH3
HO H2C C CH OC NH CH2 CH2 COOH

Structure CH3OH

Metabolism:
 absorbed in the intestine by simple diffusion, transported in the blood to the
tissues
 in the cells, in the cytoplasm, the coenzymes ( 4-P-pantotheine and CoA-SH)
are synthesized
 the coenzyme is hydrolyzed and the free pantothenic acid (90%) is excreted in
urine
Biochemical functions: Coenzyme
 4-P-pantotheine is coenzyme for acyl-transporting protein of fatty-acid
synthetase
 Dephospho-CoA is coenzyme for cytrate lyase
CoA is involved in:
activation of acetate and fatty acids, oxidation of fatty acids, synthesis of cholesterol
and other sterols, synthesis of ketone bodies
Oxidation of pyruvate to 2-oxoglutarate, production of citrate and conversion of
succinyl-CoA in Krebs cycle, synthesis of heme using succinyl-CoA
Synthesis of acetyl-choline, acetylglucosamine
Detoxification, production of hyppuric acid
Deficiency: never observed but during scientific experiments
Practical applications: calcium pantothenate, pantotheine, CoA-SH are used in a
variety in pharmacological formulations (treating skin and hair diseases and
medication of liver, cardiac muscle dystrophy) and perfumery

NIACINE, VITAMIN B5, PP

Source: yeast, eggs, milk, meat, liver, fish, vegetables and intestinal flora
Requirements: 10 mg/day
COOH CONH2

Structure: nicotinic acid N and nicotinamide N

Metabolism:
 Alimentary niacin is absorbed in the fundal part of stomach and intestin, mainly
by simple diffusion
 By blood is supplied to the liver and tissues
 Inside the cells, free vitamins exist in small amount; coenzymes are
synthesized NAD+ and NADP+;
 Coenzymes are brokendown to
ADP-ribose and nicotinamide that is excreted in urine

Biochemical functions NAD+, NADP+

 Functions of transfer of H in redox reactions
 Oxidation of carbohydrates, fatty acids, glycerol, amino acids
 Substrate conversion in Krebs cycle
 Terminal stages of dehydrogenation in respiratory chain
 NADPH+H+ is a hydrogen donor (synthesis of fatty acids, cholesterol, other
steroids)
 Substrate for synthetic reactions - substrate for DNA-ligase necessary in the
replication and repair of DNA
 Regulatory function (allosteric effector) controls the activity of citrate synthase,
MDH, NAD+-isocitrate DH, etc, controlling the rate of oxidative conversions in
Krebs cycle, the rate of gluconeogenesis
Deficiency: PELLAGRA (accompanied by hypovitaminoses of riboflavin and
pyridoxamine necessary to synthetize nicotinic acid from tryptophan).
Symptoms: skin lesions on exposure to light (photodermatitis), maldigestion,
diarrhea, dementia, neuritis, atrophy and painfulness of the tongue (fuchsine-color),
hemorrhages of gastrointestinal tract
Practical applications:
 Treatment of pellagra, dermatitis, affections of the peripheral nerves, cardiac
muscle dystrophy,
 Nicotinic acid has vasodilatative action

PYRIDOXINE, VITAMIN B6
Source:
 food - cereal, leguminous plants, meat, fish and
 intestinal bacteria
Requirements: 2-3 mg/day
H2C OH
HO CH2 OH

Structure: pyridoxine H3C N

Metabolism:
 absorption in intestine by simple diffusion,
 in blood is transported to the tissues
 in the cells it is tranformed in coenzymes pyridoxal phosphate (PALP) and
pyridoxamine phosphate (PAMP) with the use of flavin coenzymes (B2)
 the breakdown of coenzymes proceeds with dephosphorylation and oxidation
 4-pyridoxic acid is excreted in urine

Biochemical functions: coenzyme PALP takes part in nearly all classes of enzymes:
oxide-reductases, transferases, hydrolases, lyases, isomerases. The most important
reactions are decarboxylation, transamination, racemization of aminoacids,
Deficiency:
Described in children: hyperexcitability of the central nervous system, recurrent
convulsions (insufficient production of GABA, an inhibition mediator for cerebral
neurons).
In adults after treatment with isoniazid (tuberculostatic) antagonist of B6:
hyperexcitability of the nervous system, polyneuritis, skin lesions
Practical applications:
 Treatment of B6 hypovitaminosis,
 prophylaxy of isoniazid side-effects,
 treatment of polyneuritis,
 dermatitis,
 gestational toxicosis,
 impaired hepatic function,
 congenital pyridoxine-dependent anemia

FOLACIN, PTEROILGLUTAMIC ACID, VITAMIN B9

Source - food
vegetable: lettuce, cabbage, spinach, tomato, strawberry,
animal: liver, meat, egg-yolk
Requirements: 400 mg/day (800 mg/day during pregnancy)
Structure: folacin – folic acid
OH 9 10
H
4
N
5 CH2 NH CO NH C CH2 CH2 COOH
N3 6
2 8 7 COOH n
1
H2N N

Metabolism:
Absorbed in small intestine
In the intestinal mucosa tetrahydrofolic acid (THFA) and N5-methyl-THFA are formed
In the blood, 87% are in the erythrocytes and the rest in plasma
Stored in the liver, kidney, intestinal mucosa
Eliminated in urine, feces, sweat

Biochemical functions: coenzymes dihydrofolic acid (DHFA), tetrahydrofolic acid

(THFA)
  take part to the transfer of 1 carbon moiety from one coenzyme to another
coenzyme used in the synthesis of
 purines, pyrimidines, nucleic acids and cell division
 certain aminoacids (glycine from serine, methionine from homocysteine)
 Hydroxylation of aromatic aminoacids (phenylalanine, tyrosine, tryptophan)
Deficiency: MEGALOBLASTIC ANEMIA (impaired biosynthesis of nitrogenous bases,
DNA and inhibition of mitosis of hemopoietic cells)
Practical applications: treating megaloblastic anemia, stimulation of cell
proliferation, during pregnancy

COBALAMINS, VITAMIN B12

Source: food – liver, kidney, intestinal bacteria
Requirement: 2 mg/day
Metabolism:
 Castle’s factor = intrinsic factor, a glycoprotein produced in the parietal cells of
the stomach is needed
 Formation of cobalamin-intrinsic factor complex
 Binding of the complex to the epithelium of the mucosa of ileum with the
participation of Ca2+
 Transport of the complex across the mucosa by endocytosis
 Release of the vitamin B12 into the portal vein
 In the tissue, mainly in the liver and kidneys, it is converted to coenzymes:
methyl-cobalamin (methyl-B12), deoxyadenosylcobalamin (DA-B12)
 Mainly excreted in urine

Biochemical functions:
 Methyl B12 is coenzyme of homocysteine-methyl-transferase in the synthesis
of methionine; synergic action with THFA
 DA-B12 is coenzyme of methylmalonyl-CoA-mutase essential in the
combustion in the Krebs cycle of the propionyl-CoA residues
 Facilitate the deposition and production of folic acids coenzymes and involved
in the synthesis of DNA and proliferation of hemopoietic cells
Deficiency ADDISON-BIERMER ANEMIA:
 Due to the dietary deficit and inadequate absorption because of intrinsic factor
deficiency
 symptoms of disturbed hemopoiesis, affected posterior and lateral columns of
the spinal cord, increased urinary concentration of methyl-malonic acid
Practical application: treatment the megaloblastic anemia, damages of spinal cord
and peripheral nerves,

ASCORBIC ACID, VITAMIN C

Source: fresh fruits and vegetable (wild-rose fruit)
Requirement: 50-100 mg/day
Structure:
O C
O C -2H O C
HO C O
O O C
HO C
H C +2H H C
HO C H HO C H
CH 2 OH G-S-S-G 2 G-SH CH2 OH

ascorbic acid dehydroascorbic

(reduced form) (oxidized form)

Metabolism:
 Absorption by simple diffusion in the entire digestive tract, mainly in the
intestine
 In the blood is partially bound with proteins and in free state
 Free ascorbic acid can enter redox reactions
 Most ascorbic acid exists in adrenal glands, liver, lungs
 Free ascorbic acids and catabolites are excreted in urine

Biochemical functions: hydrogen donor in enzymic redox reactions, forming a redox

pair with dehydroascorbic acid; the reaction is catalyzed by ascorbate reductase
with the participation of glutathione
 Serotonine biosynthesis
 Hydroxylation of steroids during the synthesis of adrenocortical hormones from
cholesterol
  Intestinal reduction of Fe3+ to Fe2+, to provide for the iron uptake; release
of iron from its binding with the transport protein
 Conversion of folic acid to its coenzymes
 Hydroxylation of proline and lysine in collagen synthesis
Deficiency SCURVY/SCORBUTUS:
 impaired build-up of collagen and chondroitinsulphate of the connective tissue
and gradual destruction of the fibrous structure; thus the permeability of the
capillaries appears, resulting in subcutaneous hemorrhages
 Reduced possibility to use the iron in hemoglobin synthesis and the
participation of folic acid in hemopoietic cell proliferation inducing anemia
 Loosening and shedding of tooth, hemorrhage of gingivae, dolorous joints,
palor of the skin, affected bones, impaired wound healing
Practical applications: treatment of hypovitaminosis (+ folic acid, B12, Fe),
stimulating the hemopoiesis, strengthening the walls of capillaries, stimulating
regenerative processes, affected connective tissue, respiratory mucosa

FAT SOLUBLE VITAMINS

General features:
Structure
 isopren derivatives
 nonpolar structure, hydrofobic, insoluble in water but soluble in organic
solvents
Metabolism similar to the lipid metabolism:
 To be absorbed in the intestin they need the presence of the bile salts
 Transported by chylomicrons to the liver
 then stored in liver (ADK) or fat tissue (E)
Functions: important biochemical functions
 Vitamin A visual process
 Vitamin D metabolism of calcium and phosphorus; considered a pro-hormon
 Vitamin E antioxidant role
 Vitamin K role in coagulation process
RETINOLS, VITAMIN A
Source:
 All food of animal origin (mainly fish liver, pork, beef liver, egg yolk, milk,
sourcream)
 vegetal products (carrots, tomato, lettuce) contain carotenoids (provitamins A)
Requirements: 1.5 mg/day
Structure:
vitamin A1 retinol 1 retinal 1 retinoic acid 1

H3C CH3 CH3 CH3 H H3C CH3 CH3 CH3

H3C CH3 CH3 CH3
CH2 OH C COOH
O
CH3 CH3 CH3

vitamin A2 retinol 2 (dehydroretinol)

H3C CH3 CH3 CH3

CH2 OH

CH3

Provitamins A = carotenes , , ; the most active, -carotene is oxidized in the

intestinal mucosa at the central double bond under the action of carotene
dehydrogenase resulting 2 molecules of active retinal that is reduced to retinol
Metabolism:
 the bile acids are needed for the absorption of vitamin A in the intestin
 in the intestinal mucosa retinol forms esters with fatty acids, transported in the
chylomicrons
 in the plasma retinol is bound with a protein (1-globulin) and transported to
the tissues
 in the retina, retinol is converted to retinal, a part of rhodopsin (light sensitive
protein) and plays an important role in the perception of the visible light.
 the retinol esters are stored in the liver;
  in the liver it is oxidized to retinal and further to retinoic acid which is excreted
in bile as glucuronide

Biochemical functions - control of:

 Normal growth and cell differentiation (embryo, young organisms)
 Division and differentiation of fast proliferating tissues (cartilage, bone,
spermatogenetic epithelium, placenta, skin epithelium, mucosa) retinoic acid
acts on synthesis of glycoproteins in growing bones and soft tissues)
 Photochemical visual act:
 When the rodopsine absorbs light 11-cis retinal is transformed in trans retinal
producing the nervous stimulation
 Rodopsine (the visual pigment) is a conjugated protein formed of a protein
opsine and Δ11-cis retinal stereoisomer
 The complex dissociates in opsin and trans retinal which is reduced by retinal
reductase in the presence of NADH+H+ to trans retinol (vit A1)
 Light mediates the association of 11-cis retinal with opsin to regenerate
rodopsin

Deficiency:
 Deficiency of dark-adaptation and night blindness
 Retardation of growth
 Hyperkeratosis of skin follicles, mucosa dryness, xerophtalmia, keratomalacia
 Dysordered reproductive function (failure of spermatozoa to fertilize)
Practical application: mixtures of natural vitamin A and synthetic analoques are used
to treat hypovitaminoses, visual excessive use, stimulate growth and development
of children

CALCIFEROLS, VITAMIN D
Source - food of animal origin (liver, butter, milk, yeast), vegetable oils
Requirements: 12-25g/day in child; less for adult
Structure: derivative of steroids,
  Vitamin D2 = ergocalciferol is produced from ergosterol = provitamin existing
in plants
 Vitamin D3 = cholecalciferol is produced in the human skin, from 7-
dehydrocholesterol by UV radiation,
 Vitamin D4 = dehydroergocalciferol
They are biologically inactive

R
CH3 H 3C
CH 3
17 CH 3
CH2
CH 2 CH 3

HO HO

7-dehydrocholesterol cholecalciferol (vitamin D3)

Metabolism:
 Absorption in the intestin with the help of bile acids
 Excreted as chylomicrons transported in the blood to the liver
 In the liver: cholecalciferol and ergocalciferol are hydrolyzed by cholecalciferol
25-hydroxylase, in the endoplasmic reticulum, resulting 25-hydroxy
cholecalciferol and 25-hydroxy ergocalciferol
 They are carried by a calciferol-binding protein to the kidney where, under the
action of 1-hydroxylase the 1,25-dihydroxycalciferol is synthesized; this is the
active form of vitamin D
 Vitamin D is stored in the fat tissue
 Eliminated in feces unaltered, oxidized, conjugated

H3C H3C
CH3 CH3
CH3 25 CH3 25
OH OH
OH
CH2 CH3 CH2 CH3
1

HO HO

25-hydroxy cholecalciferol 1,25-dihydroxycalciferol

Biochemical function: control of calcium and phosphate ions transport across the
cell membrane acting as a regulator factor for their concentration in the blood:
1. Transport of calcium and phosphate ions across the epithelium of intestinal
mucosa
2. Mobilization of calcium from the bones
3. Reabsorption of calcium and phosphate in the renal tubules

Deficiency: RICKETS - in children, caused by

 the inadequate intake of vitamin D
 reduced exposure to UV radiations
 low sensitivity of the tissues to calciferols
Low concentration of calcium and phosphate in the blood determine impaired
bone mineralizatrion, resulting in deformation of the bones of limbs, skull,
thorax
Relative deficiency is noticed in the patients with chronic diseases of liver and
kidney
In adults whose growth is complete, the bones are translucid and there is an
increased risk for fracture = OSTEOMALACIA
Hypervitaminosis: demineralization of bones with high risk of fracture, calcification
of organs (blood vessels, lungs, kidney)
Practical application: prophylaxis and treatment of rickets, osteoporosis,
tuberculosis of bones, joints and skin

TOCOFEROLS, VITAMIN E
Source: vegetal oil (sun flower, corn, cottonseed, olive, wheat seedling oil)
Requirements: 20-50 mg/day
Structure:
R
1
HO

R2 O
CH3
R3

There are -, -, -, -tocopherols depending on R

 CH3
HO

H3C O
CH3
CH3

-tocopherol

Metabolism:
 Absorption needs the presence of fats and bile acids as emulsifying agents
 In intestine absorbed by simple diffusion
 Transport as chylomicrons through lymph and blood, complexed with
lipoproteins, to organs and tissues where it is concentrated in membranes
 Most of it is stored in adipose tissue, liver, skeletal muscles
 Eliminated in feces; metabolites eliminated in urine

Biochemical functions:
 A biological antioxidant that provides the stability of cell membranes. Controls
the rate of free-radicals reactions in the living cells by inhibiting spontaneous
chain reactions of peroxide oxidation of unsaturated lipids in biomembranes
 Increases the biological activity of vitamin A by protecting its unsaturated side
chains from peroxide oxidation
Deficiency: in premature infants leading to hemolytic anemia
Practical application:
 Antioxidant to prevent excessive lipid peroxide accumulation
 Prophylaxis of sterility and abortion, liver diseases, muscular atrophy,
congenital diseases of erythrocyte membrane

NAPHTOQUINONE, VITAMIN K
Source: green vegetables, liver, intestinal bacteria
Requirements: 2 mg/day
Structure: quinones with an isoprene side chain; various forms that differ in the
length and degree of unsaturation of the long side chain; there are
  phylloquinones (vitamins K1) in plants and
 menaquinones (vitamins K2,, MQ) synthesized by intestinal bacteria or derived
from naphtoquinones metabolism in the tissues
O
CH3

Metabolism:
 Bile acids and pancreatic lipase are needed for the intestinal absorption
 Transported with the chylomicrons; in the blood plasma it is bound with
albumins to be stored in the liver, spleen, heart
 In the tissues they are transformed to MQ-4 that serves as biologically active
form of vitamin K
 The end products of catabolism are excreted in the urine

Biochemical functions:
 control of the blood coagulation – participate to the build-up of
 factor II (prothrombin),
 factor VII (proconvertin),
 factor IX (Christmas),
 factor X (Stewart);
 conversion of pro-prothrombin to prothrombin in the liver, triggers fibrin clot
formation.
Deficiency
 Predisposition to hemorrhagic disease
 In adults the intestinal flora provides a complete supply; in children the
alimentary deficit is described
 Causes:
 suppression of intestinal flora by drugs
 disease of gallbladder with reduced production of bile acids, needed for
absorption;
  disease of liver involved in the activation of vitamin K and synthesis of
coagulation factors.
Practical application: treatment of hemorrhagic diseases

VITAMIN F, ESSENTIAL FATTY ACIDS

Source: exclusively vegetal
Structure: polyunsaturated fatty acids
Functions:
 components of the phospholipids and other structural lipids of the cell and
intracellular membranes
 growth and normal development of the organism
 normal ovulation
 prevent the dermatitis and dryness of skin
 precursors of prostaglandins
Deficiency:
 lack of vitality in newborn, stop of growth,
 reduced reproductive capacity
 fragile capilaries