Download 7. vitamins - Biochemistry Notes

Medical Biochemistry
Molecular Principles of Structural Organization of Cells
7. VITAMINS
Vitamins are low molecular organic compounds,
indispensable for the normal vital activity of the organisms
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 1. WATER-SOLUBLE VITAMINS
Vit
name
Chemical name
Chemical forms
Biologically inactive
Physiological
name
Biologically active
Derivatives
Thiamine
Coenzymes
Thiamine diphosphate
Thiamine triphosphate
aneuritic
FMN, FMNH2
FAD, FADH2
Pantotheine-4-phosphate
CoA-SH
NAD+, NADH+H+,
NADP+, NADPH+H+
PALP, PAMP
growth factor
Folacin
Tetrahydrofolic acid (TH4) and
derivatives with 1 carbon
radicals
growth factor
Methylcobalamin
deoxyadenosylcobalamin
antianemic
Ascorbic acid
Cyancobalamin
Oxocobalamin
Dehydroascorbic acid
H
Biotin
Biotin
B4
P
Choline
Bioflavonoids
Choline
B8
Inositol
N
Lipoic acid
BT
Carnitine
B13
Orotic acid
B15
U
H
Para-amino-benzoic
acid (PABA)
B1
Thiamine
B2
Riboflavin
B3
Pantothenic acid
Pantothenate
B5(PP)
Niacin
B6
Pyridoxine
Nicotinamide, Nicotinic
acid
Pyridoxine, Pyridoxol
Pyridoxamine
B9
(Bc)
B12
Folacin (folic acid)
Cyanocobalamin
C
Ascorbic acid
antipellagric
antidermatitis
antiscorbutic
Carboxybiotin
antiseborrheic
Phosphocholine
Flavines: rutin, quercetin
Flavonones: hesterindin,
catechol complex
Inositol, mesoinositol
Lipoic acid
vasoformative
s
lipamide (oxidized and
reduced)
Carnitine, Acylcarnitine
Orotic acid
Orotodin-5-phosphate
growth factor
Pangamic acid
Pangamic acid
antianoxic
S-methylmethionine
S-methyl-methionine
Methylthioaminosulphoniu
m
Folic acid
antiulcerous
Para-amino-benzoic
acid (PABA)
Microbial
vitamin
CLASSIFICATION 2. FAT-SOLUBLE VITAMINS
Vit
name
Chemical name
Chemical forms
Biologically inactive
Physiologic
al name
Biologically active
Derivatives
Coenzymes
A
Retinol
Retinyl acetate
Retinyl palmitate
Retinal, retinol,
retinoic acid
antixeroftal
mic
D
Calciferols
Ergocalciferol (D2)
Cholecalciferol (D3)
1,25-dihydroxycalciferol
antirahitic
E
Tocoferols
α,β,γ,δ –tocoferols,
tocotrienols
antisterilic
K
Naphtoquinones
Phylloquinones(K1)
Menaquinone (K2)
antihemorrh
age
F
Essential fatty
acids
Ubiquinone
(coenzyme Q)
Linoleic acid,
linolenic acid,
arachidonic acid
Ubiquinone (CoQ)
Ubiquinol (CoQH2)
WATER-SOLUBLE VITAMINS AND THEIR COENZYMES
Vitamin
Coenzyme form
Type of catalyzed reaction
Chemical group
B2 Riboflavin
FAD, FMN
Oxydoreduction (H transfer)
H (electrons)
PP Niacin
NAD+, NADP+
Oxydoreduction (H transfer)
H (electrons)
B1 Thiamin
T-PP
Acyl group transfer
Aldehyde group transfer
Decarboxylation of ketoacids
R-COR-CO-COOH
Lipoic acid
T-PP-LSS
Acyl group transfer
Decarboxylation of ketoacids
R-COR-CO-COOH
B3 Pantothenic acid
CoA-SH
Acyl group carrier and transfer
R-COOH, R-CO-
B6 Pyridoxine
PALP, PAMP
Aminogroup transfer
R-CHNH2-COOH
Biotin
Biotin, biocytin
Carboxyl group removal or transfer
COO-, CO2
Folic acid
FH2, FH4
One-carbon group transfer
-CH3, -CHO
Vitamin B12
Coenzyme B12
Shift of H adjacent C
Methyl group transfer
-CH3
Ascorbic acid
Uncertain, may serve as cofactor in
hydroxylation reaction
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)
Vitamin
Daily requirement
Deficiency symptoms
A retinal
1.0 mg
Night blindness, xerophtalmia
D calciferol
5 μg (synthesis in skin)
Rickets, osteomalacia
E tocopherols
10 mg
Muscle weakness, hemolysis
K menaquinone
1.4 mg (synthesis by intestinal
bacteria
Synthesis in the body
Delayed blood coagulation
B1 thiamine
1.4 mg
Polyneuritis (beriberi)
B2 riboflavin
1.7 mg
Dermatitis
B3 pantothenic acid
7 mg
Paresthesias, cramps in extremities
B5 (PP) niacin
18 mg (synthesis in the body from
tryptophan)
Pelagra
B9 folacin
0.4 mg
Megaloblastic anemia
Pteridine (biopterin)
Synthesis in the body
B6 pyridoxal
2.2 mg
Dermatitis, psychic disorders
B12 cobalamin
3 μg
Anemia, neuropathy
C ascorbic acid
60 mg
Scurvy
H biotin
0.15 mg (synthesis in the body by
intestinal bacteria)
Dermatitis
Fat soluble vitamins
Q ubiquinone
Water soluble vitamins
VITAMIN BALANCE
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)
WATER SOLUBLE VITAMINS
Complex B - General features
1.
2.
3.
4.
5.
soluble in water
coenzymes in biochemical processes of great importance
activators - stimulate metabolic processes and regulate them
growth factors for microorganisms and young organisms
the most of them are synthesized by intestinal microflora
(thiamine, pantothenic acid, nicotinamide, pyridoxine,
folacine, corinoids, PABA)
Complex C: ascorbic acid, flavonoids (C2)
WATER SOLUBLE VITAMINS
THIAMINE, VITAMIN B1
Source: plants (coarse bread, pea, beans) and meat products
Active form: thiamine diphosphate (T-PP)
Daily requirement: 1-3 mg
NH2
NH2
H2
Structure:
H2
CH3
CH3
C
N
H3C
N
NH2
S
C
N
N+
CH2 CH2
OH
H3C
N
N+
NH2
S
CH2 CH2
O
O
O P
O P
OH
OH
OH
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 2oxiglutarate (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
Structure
N
N
H3C
C O
H3C
N
C
NH
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.
NH2
O
H3C
H3C
CH2
(CHOH)3 CH2
N
N
N
C
C O
NH
O P
O
OH
OH
H3C
H3C
CH2
(CHOH)3 CH2
N
N
N
O
O
FMN
C
FAD
C O
O
P
OH
O
O
P
N
N
O
OH
N
CH2
NH
H
O
H
H
OH
H
OH
N
Biochemical functions:
– transfer of electrons and H+ in the respiratory chain
– mitochondrial oxidation of pyruvate, succinate, 2-oxoglutarate, glycero phosphate
– oxydation of biogenic amines, aldehydes.
Defficiency:
– lessions of the cornea, conjunctiva dry and inflammated,
– mucosa of lips red, dried, craked,
– skin desquamating
Practical application:
– treating inflammation of skin, cornea, conjunctiva: dermatitis, poor
healable wounds and ulcers of skin, keratitis, conjunctivitis
– treating intoxication with CO,
– medication of liver, muscular affection after excessive effort
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 CoASH) are synthesized
– the coenzyme is hydrolyzed and the free pantothenic acid (90%) is
excreted in urine
Pantothenic acid
CH3
CH3
H2C
O
O
P
C
CH
OC
CH3 OH
OH
NH
NH2
N
P
O
OH
N
CH2 O
H
H
H
H
OH
O
PO3H2
CoA-SH
CH2
CO
NH
CH2
CH2
SH
H2C C
CH
OC
NH CH2
O CH3 OH
O
P OH
NH2
N
N
O
N
O
O
CH2
O
P OH
N
O
N
CH2 O
H
H
H
H
OH
O
PO3H2
Acetyl-CoA
N
CH2
CO NH
CH2
CH2
S
CO
CH3
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 g/day
CONH2
COOH and nicotinamide
Structure: nicotinic acid
Metabolism:
N
N
– 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
NAD+
NADP+
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
Structure:
pyridoxine,
H2C OH
HO
CH2 OH
Metabolism:
H3C
N
pyridoxal,
pyridoxamine
HC O
HO
H3C
CH 2 OH
N
HO
H3C
CH2 NH2
CH2 OH
N
– 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)
HC O
HO
H3C
CH 2 O PO3H2
N
HO
CH 2 NH 2
CH 2 O PO3H2
H3C
N
PALP
PAMP
– 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 g/day (800 g/day during pregnancy)
Structure: folacin – folic acid
OH
N3
2
9
4
N
5
1
8
H2N
10
CH2 NH
6
7
H
CO NH C CH2 CH2 COOH
COOH
n
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)
N
H2N
OH
OH
OH
N
N
CH 2 R
CH
N
H2N
N
N
H
CH 2 R
CH 2
N
H2N
H H
N
CH 2 R
N
H
CH 2
F
FH2
FH4
– 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 g/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: 50-100mg/day
O C
Structure:
HO
HO
H
HO
C
O
C
C
C H
CH 2 OH
ascorbic acid
(reduced form)
-2H
+2H
G-S-S-G
2 G-SH
O
O
O
H
HO
C
C
O
C
C
C H
CH 2 OH
dehydroascorbic acid
(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 prohormon
– Vitamin E antioxidant role
– Vitamin K role in coagulation process
FAT-SOLUBLE VITAMINS
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: 1.5mg/day
Structure:
vitamin A1 retinol 1
H3C
CH3
CH3
CH3
CH2 OH
H3C
retinal 1
CH3
CH3
retinoic acid 1
CH3
C
H H3C
CH3
O
CH3
CH3
vitamin A2 retinol 2 (dehydroretinol)
H3C
CH3
CH3
CH3
CH3
CH2 OH
CH3
CH3
CH3
COOH
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
H3C
CH 3
CH 3
CH 3
H3C
H3C
15
15
CH 3
CH 3
CH 3 H3C
CH 3
CH 3
CH 3
CH 3
CH 3
CH 3
CH 3
15
CH 3
H3C
H3C
CH3
CH3
+ 2 H2 O
CH 3
-carotene
CH 3 H3C
CH 3
 -carotene
15
15
CH 3
15
CH 3
-carotene
H3C
H3C
CH 3 H3C
CH 3
CH3
CH2 OH
CH3
2 retinol 1
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
Photochemical visual act:
LIGHT
LUMINOPSINE
RODOPSINE
OPSINE
H3C
CH 3
CH 3
H3C
11
CH 3
CH 3
CH 3
12
H3C
CH 3
NADH+H+
retinol dehydrogenase
NAD+
H3C
CH 3
CH 3
CH O
11-cis retinal
CH 3
trans retinal
NADH+H+
retinal reductase
NAD+
H3C
11
CH 3
CH 3
CH 3
CH 2 OH
12
CH 3
11-cis retinol
CH 3
H3C
CH 2 OH
H
C O
trans retinol
Rodopsine (the visual
pigment) is a conjugated
protein formed of a protein
opsine and Δ11-cis retinal
stereoisomer
When the rodopsine
absorbs light 11-cis retinal is
transformed in trans retinal
producing the nervous
stimulation
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 7dehydrocholesterol by UV radiation,
– Vitamin D4 = dehydroergocalciferol
They are biologically inactive
R
CH3
H3C
CH3
17
CH2
HO
7-dehydrocholesterol
CH2
CH3
CH3
HO
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
CH2
25
CH3
CH3
OH
CH3
25
OH
CH2
1
HO
25-hydroxy cholecalciferol
HO
1,25-dihydroxycalciferol
CH3
OH
CH3
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
R
Structure:
1
HO
R2
O
R3
CH 3
There are -, -, -, -tocopherols depending on R
CH 3
HO
H3C
O
CH 3
CH 3
-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
O
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
linoleic
18
Δ9,12
linolenic
18
Δ9,12,15
arachidonic
20
Δ5,8,11,14
CH3-(CH2)4-CH=CH-CH2-CH=CH-(CH2)7-COOH
CH3-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)7-COOH
CH3-(CH2)4-CH=CH-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)3-COOH
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