ENDOCRINE SYSTEM, METABOLISM: Vitamins

Vitamins
ASCORBIC ACID (VITAMIN C).................................................................................................................3

BIOTIN (VITAMIN H)................................................................................................................................5

NIACIN (NICOTINIC ACID, VITAMIN PP).................................................................................................6

PANTOTHENIC ACID.................................................................................................................................8

THIAMINE (VITAMINE B1)........................................................................................................................8

RIBOFLAVIN (VITAMIN B2).....................................................................................................................10

PYRIDOXINE (VITAMIN B6).....................................................................................................................11

RETINOL (VITAMIN A)...........................................................................................................................12

TOCOPHEROL (VITAMIN E)...................................................................................................................14

Cobalamin (VITAMIN B12) → see HEMATOIMMUNOLOGY

Folic acid → see HEMATOIMMUNOLOGY

Vitamin K → see HEMATOIMMUNOLOGY

Cholecalciferol (VITAMIN D3) → see p. 2731 (11-13), 2756, 2754 (9)

Cofactor form: Disease caused by

Vitamin RDA (sources)
associated enzymes deficiency

Ascorbic acid Ascorbate: Scurvy (bleeding gums, 60-90 mg

perifolliculitis, nonhealing
(vit. C) 1. Prolyl and lysyl hydroxylases wounds, bones, dentin) (citruses, raw vegetables)

2. Dopamine -hydroxylase

Biotin Biotin: Multiple carboxylase not established

deficiency (seborrheic
(vit. H) four carboxylases dermatitis, glossitis, (30-300 μg)
ketoacidosis, retardation)
(intestinal m/o)

Folic acid* Tetrahydrofolate: Megaloblastic anemia, birth 400 g

defects
enzymes that transfer one-carbon (green leafy vegetables,
units liver, yeast)

Niacin NAD+, NADP+: Pellagra (3D: dermatosis, 16-20 mg

(nicotinic acid, diarrhea, dementia; glossitis)
vit. PP) dehydrogenases (10 susidaro iš Trp;
90 gaunama su įvairiu

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
maistu)

Pantothenic acid Coenzyme A: nepasitaiko not established (5-10 mg)

various enzymes (įv. maistas, intestinal

m/o)

Thiamine Thiamine pyrophosphate (TPP): Dry beriberi (leg 1.2-1.5 mg

polyneuropathy), wet
(vit.B1) 1. -keto acid decarboxylases beriberi (high output cardiac (įv. maistas)
(carbohydrate metabolism) failure), Wernicke-
Korsakoff syndrome
2. transketolase

(pentose monophosphate pathway)

Riboflavin FMN, FAD: Ariboflavinosis (angular 1.3-1.7 mg

stomatitis, cheilosis,
(vit.B2) Oxidoreductases (protein seborrheic dermatitis, (įv. maistas, ypač pieno
metabolism, etc) corneal neovascularization) produktai)

Pyridoxine Pyridoxal phosphate: pasitaiko retai (skin and 1.7-2 mg

mucosa, convulsions,
(vit.B6) 1. Enzymes of amino acid metabolism sideroblastic anemia) (intestinal m/o, įv.
maistas)
2. Glycogen phosphorylase

Cobalamin 5’-Deoxyadenosylcobalamin: Pernicious anemia 2-6 g

(vit.B12)* (megaloblastic anemia +
Methylmalonyl CoA mutase subacute combined (intestinal m/o, visi
degeneration of spinal cord) produktai išskyrus
Methylcobalamin: augalinius)
Homocysteine methyltransferase

Cofactor form: Disease caused by

Vitamin RDA (sources)
primary function deficiency

Retinol 11-cis retinal: Nyctalopia, xerophthalmia, 1000 g (3000 IU)

Bitot’s spots, epithelial retinol equivalents
(vit. A) rhodopsin (vision) hyperkeratosis, reproduction
disorders (dark green leafy and
yellow vegetables, fish
liver oil)

Tocopherol antioxidant Hemolytic anemia, 8-10 mg (15-30 IU)

spinocerebellar disease,
(vit. E) reproductive disorders (?) (vegetables, seed oil)

Vitamin K* various forms of vitamin K: Bleeding 65-120 g

γ-carboxylation of glutamate residues (intestinal m/o, plants)

in blood-clotting enzymes (II, VII,
IX, X)

Cholecalciferol 1,25-dihydroxycholecalciferol: Rickets (children), 10-20 g cholecalciferol

osteomalacia (adults) = = 400-800 IU vit. D
(vit.D3) regulation of calcium metabolism
(sintezuojamas odoje UV
poveikyje; fish liver oils,
egg yolk, fortified milk)

2733 (2)
ENDOCRINE SYSTEM, METABOLISM: Vitamins
*see HEMATOIMMUNOLOGY

RDA (Recommended Daily Allowance) (from "MERCK Manual", 17 ed., 1999): see also 2732 (5) p.

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ENDOCRINE SYSTEM, METABOLISM: Vitamins

ASCORBIC ACID (VITAMIN C)

RDA
60 mg (pregnancy - 70 mg, lactation - 95 mg)

SOURCES
1. Citrus fruits, tomatoes, broccoli, cabbage

2. Raw or minimally cooked (vit.C lengvai oksiduojasi) vegetables

METABOLISM
vit. C is not metabolized.

šalinasi su šlapimu.

FUNCTIONS
- strong reducing agent - reversibly oxidized and reduced, functions as REDOX SYSTEM in cell:

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
1. Activates HYDROXYLASES that hydroxylate Pro and Lys in procollagen - helps maintain integrity of
substances of mesenchymal origin (connective tissue, osteoid tissue, dentin) - essential for wound
healing and recovery from burns.

2. Metabolism of Phe and Tyr (synthesis of catecholamines) – DOPAMINE β-HYDROXYLASE

3. Facilitates iron absorption (redukuoja Fe3+ į Fe2+).

4. Antioxidant – protects against free radicals.

5. Protects folic acid reductase (folic acid → folinic acid).

SCURVY (s. SCORBUTUS)

ETIOLOGY
1. Food idiosyncrasies or improper diet (e.g. "ulcer diet" - achlorhydria decreases amount absorbed)
< 10 mg/d.

2. Heat (e.g. sterilization of formulas, cooking) can destroy vitamin C in food.

3. Pregnancy, lactation, inflammatory diseases, surgery, burns, thyrotoxicosis - increased demands.

4. Diarrhea - increased fecal loss.

5. Cold or heat stress - increased urinary excretion.

PATHOLOGY
Defective formation of intercellular cement substances (in connective tissues, bones, dentin):

1) weakened capillaries → hemorrhage

2) defects in bone and related structures; endochondral growth ceases (osteoblasts fail to form osteoid
tissue), instead, fibrous union forms between diaphysis and epiphysis, costochondral junctions
enlarge (“scorbutic rosary” ≈ in rickets).

3) hemorrhagic areas are organized avascularly, so that wounds heal poorly and break open easily.

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ENDOCRINE SYSTEM, METABOLISM: Vitamins

SYMPTOMS & SIGNS

Latent period 3-6 months.

Pradžioje - lassitude, weakness, irritability, weight loss, vague myalgias and arthralgias.

Overt scorbutic symptoms:

1. Pirmasis simptomas - spontaneous hemorrhages in any part of body.

 patognomiška - hyperkeratotic hair follicle with surrounding hyperemia (perifolliculitis),

perifollicular petechiae and ecchymoses esp. in lower limbs).

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ENDOCRINE SYSTEM, METABOLISM: Vitamins

 multiple splinter hemorrhages may form crescent near distal nail end (more extensive than
those in bacterial endocarditis).

2. Bleeding gums - gums become swollen (hyperplastic), purple, spongy, and friable; they bleed
readily (gingivitis).

secondary infection, gangrene, and teeth loosening eventually occur.

3. Old scars break down, new wounds do not heal.

4. Bone lesions do not occur in adults!

vaikams džn. kartu esti ir vit.D hipovitaminozė → osteopathia hemorrhagica infantum (s.
scurvy rickets).

5. Arthritis resembling RA (due to bleeding around or into joint)

6. Heart failure, inanition and debility.

Negydant – mirtis!

see 2733 (4a) p.

LABORATORY DIAGNOSIS
1. [Ascorbic acid]↓:

a) in plasma

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
b) more significant in WBC-platelet layer of centrifuged blood.

c) when vit. C stores are depleted, little appears in urine after test dose of vitamin C.

2. Positive capillary fragility test

3. Anemia (hypochromic, normocytic or microcytic)

Bleeding and coagulation times are normal!

PROPHYLAXIS
Vitamin C 60 mg/d is fully protective!

Huge doses of vitamin C (≈ 10 g/d):

a) neapsaugo nuo common cold, neįtakoja progress of malignant disease or atherosclerosis.

b) acidify urine (vit. C stipri rūgštis) - predispose to urinary calculi from oxalate.

c) diarrhea from osmotic effects.

d) promote iron overload.

TREATMENT
In adults, ascorbic acid 300-500 mg/d for 2 wk or until signs have disappeared.

signs and symptoms usually disappear over 1-2 wk.

BIOTIN (VITAMIN H)
RDA
unknown (30-100 μg?)

SOURCES
 intestinal m/o susintezuoja pakankamus kiekius, todėl dietary source is normally not necessary.

 dietary sources: liver, egg yolk, yeast.

METABOLISM
Biotin is not modified.

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
Biotin functions as prosthetic group:

 biotin holocarboxylase synthetase kovalentiškai prijungia biotiną prie apoenzimo.

 biotinidase removes biotin from apoenzyme (during protein turnover) and allows biotin to
be recycled.

FUNCTIONS
Biotin is carrier of CO2 in carboxylation reactions.

Four CARBOXYLASES require biotin (amino acid and fatty acid metabolism, gluconeogenesis):

1. Pyruvate carboxylase (pirmoji gliukoneogenezės reakcija: pyruvate → oxaloacetate)

2. Acetyl CoA carboxylase (pirmoji fatty acid synthesis reakcija: acetylCoA → malonylCoA)

3. Propionyl CoA carboxylase (fatty acids su nelyginiu C atomų skaičiumi oksidacija)

4. -Methylcrotonyl CoA carboxylase

DEFICIENCY & DEPENDENCY

ETIOLOGY
Deficiency:

1. Antibiotikoterapija

2. Nevirtų kiaušinių vartojimas (raw egg white contains AVIDIN – has very high affinity to biotin –
prevents absorption).

Dependency – genetic defects of:

Biotin holocarboxylase synthetase

Biotinidase

SYMPTOMS & SIGNS

- MULTIPLE CARBOXYLASE DEFICIENCY: see 2733 (5a) p.

Deficiency:

1. Seborrheic dermatitis, hair loss (vit. H – vok. Haut – oda)

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
2. Anorexia and glossitis

3. Ketoacidosis

4. Muscular pain

Dependency:

1. Developmental retardation

2. Defects in T-cell and B-cell immunity

LABORATORY DIAGNOSIS
Urinary excretion of various organic acids – karboksilazių nepanaudoti (arba metabolizuoti
alternatyviais keliais) substratai.

TREATMENT
Deficiency – biotin 150-300 μg/d.

Dependency – large doses of biotin (5-50 mg/d).

NIACIN (NICOTINIC ACID, VITAMIN PP)

- part of vitamin B complex.

Therapeutic uses:

1) pellagra (vit. PP – pellagra-preventing)

2) vasodilator

3) hyperlipidemia (cholesterol-lowering and HDL-raising agent) see 780 p. (in BIOCHEMISTRY)

RDA
- up to 20 mg.

1 niacin equivalent = 1 mg niacin = 60 mg dietary Trp

SOURCES
10% susidaro organizme iš Trp.

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
90% turi būti gaunama su maistu: cereals, meat, yeast, etc. Termostabilus.

METABOLISM & FUNCTIONS

Niacin is precursor for NAD+ and NADP+ - coenzymes for DEHYDROGENASES (oxidation-reduction
reactions) – vital in cell metabolism!

PELLAGRA

ETIOLOGY
Primary deficiency - in areas where maize (Indian corn) forms major part of diet:

– bound niacin, found in maize, is not assimilated in intestinal tract unless it has been
previously treated with alkalis (as in preparation of tortillas).

– corn protein is deficient in tryptophan.

Secondary deficiency:

isoniazid therapy (drug replaces niacinamide in NAD)

malignant carcinoid tumor (Trp sunaudojamas serotonino gamybai)

Hartnup disease (sutrikusi Trp absorbcija žarnyne ir reabsorpcija inkstuose)

diarrheas, cirrhosis, alcoholism, etc

SYMPTOMS & SIGNS

Dermatosis + diarrhea + dementia (+ death) see 2733 (6a) p.

1. Cutaneous lesions (dermatosis) - acute photosensitive rash: sunlight causes CASAL necklace and
butterfly-shaped lesions on face.

 galimi ir kitokie odos pažeidimai.

 distribution of lesions (at trauma points, usually bilaterally symmetric) is more

characteristic than their form.

 secondary infections are common.

2. Mucous membrane symptoms - scarlet glossitis and stomatitis; ulcerations may appear.

3. GI symptoms - serious diarrhea, often bloody because of GI hyperemia and ulceration.

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4. Neuro symptoms: (1) encephalopathic syndrome (cognitive deficits*, personality changes that
progress to delirium), (2) peripheral neuropathy.

 differentiating neuro symptoms from those in thiamine deficiency is difficult.

*irreversible dementia can result if deficiency is not treated

LABORATORY DIAGNOSIS
Urinary excretion of N´-methylnicotinamide (NMN) is decreased (< 0.8 mg/d suggests niacin
deficiency).

TREATMENT
Niacinamide* 300-1000 mg/d orally.

*niacin can cause flushing, itching, burning, tingling.

Multiple deficiencies of B vitamins and protein often occur together - other B-complex vitamins
should also be given in therapeutic dosages.

e.g. neuropathy does not improve with niacin supplements; symptoms improve only when
thiamine and pyridoxine are added.

PANTOTHENIC ACID
- part of vitamin B complex.

RDA
- not established (4-7 mg – safe & adequate)

SOURCES
- widely distributed in various foods + sintezuoja žarnyno flora.

METABOLISM & FUNCTIONS

- precursor of coenzyme A (acyltransfer cofactor).

DEFICIENCY is rare in humans.

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THIAMINE (VITAMINE B1)

RDA
1-1.5 mg (0.5 mg/1000 kcal)

SOURCES
- įvairus maistas; kepenyse atsargos nedidelės (≈ 2 savaitėms).

 total body store is 30-100 mg (in heart, skeletal muscle, liver, kidneys, brain).

METABOLISM & FUNCTIONS

ATP pagalba iš thiamine susidaro aktyvi forma thiamine pyrophosphate (TPP) - coenzyme for:

1) α-KETO ACID DECARBOXYLASES (carbohydrate metabolism) t.y. pyruvate dehydrogenase

(decarboxylase) – smulkiau žr. 704 p. (in BIOCHEMISTRY)

2) TRANSKETOLASE (pentose monophosphate pathway) – smulkiau žr. 693 p. (in BIOCHEMISTRY)

BERIBERI
(Singhalese word beri – weakness)

ETIOLOGY

Primary deficiency - inadequate thiamine intake (esp. in people subsisting on highly polished rice).

Secondary deficiency is caused by:

increased requirement (hyperthyroidism, pregnancy, lactation, fever).

impaired absorption (prolonged diarrheas, hyperemesis gravidarum).

impaired utilization (severe liver disease).

alcoholism - combination of decreased intake, impaired absorption and utilization, increased

requirements, and possibly apoenzyme defect!

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
frequent, long-term, or highly concentrated dextrose infusions, coupled with low thiamine intake, may
precipitate thiamine deficiency!

PATHOLOGY
Neural changes:

– axon loss in peripheral nerves, particularly of legs (distal segments are affected earliest
and most severely).

– degeneration can occur in all tracts and columns of spinal cord.

– hemorrhagic polioencephalitis in severe deficiency.

Heart is dilated and enlarged.

Vasodilation occurs and can result in some edema before frank high-output heart failure occurs.

SYMPTOMS & SIGNS

WET BERIBERI - high output cardiac failure with vasodilation and warm extremities.

see 2733 (8a) p.

DRY BERIBERI - bilateral symmetric polyneuropathy (as in alcoholics!!!): see Psy21 p.

– predominantly lower extremities, distal parts - severe burning dysesthesias, sensory loss,
weakness and wasting, trophic changes (shiny skin, hair loss), early absent ankle jerks!

– arms may be affected after legs.

CEREBRAL BERIBERI (WERNICKE-KORSAKOFF SYNDROME)

CNS changes result from severe acute deficiency superimposed on chronic deficiency:

Korsakoff syndrome – amnesia → confusion, confabulations; see S6 p.

Wernicke syndrome – ataxia, ophthalmoplegia. see Psy21 p.

LABORATORY DIAGNOSIS
a) serum [thiamine] lacks sufficient sensitivity and specificity to be used alone.

b) blood pyruvate and lactate↑

c) 24-hour urinary excretion of thiamine↓

d) RBC transketolase activity↓ - most accurate indicator of tissue stores! (increases after TPP
administration - TPP effect)

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
e) therapeutic trial of thiamine:

panašias polineuropatijas sukelia diabetas ir alkoholizmas, bet jos do not respond to thiamine.

heart failure responds poorly to digitalis or diuretics; therapeutic trial of thiamine → edema
and congestion respond in few hours!

PROPHYLAXIS
- su gliukozės infūzijomis kartu skirti tiaminą (iki 100 mg i/v, nes netoksiškas – perteklius lengvai
pasišalina su šlapimu) – ypač esantiems neaiškios kilmės komoje.

TREATMENT
Negydant mirtis Recovery from neurologic deficits is often incomplete!

 thiamine up to 100-200 mg/d parenteraliai + turtinga dieta.

 dažnai lydi other B-complex deficiencies, and multiple water-soluble vitamin therapy at 5-10
times RDA is advisable for several weeks.

 magnesium (cofactor for transketolase) - to correct thiamine resistance and frequently

accompanying hypomagnesemia.

 hyponatremia should be corrected slowly (rapid correction may cause central pontine
myelinolysis).

RIBOFLAVIN (VITAMIN B2)

RDA
1.2-1.5 mg (iki 1.7 mg)

SOURCES
- įvairus maistas, ypač pieno produktai.

METABOLISM & FUNCTIONS

intestinal mucosa: riboflavin → FMN

liver: FMN → FAD

FMN ir FAD yra OKSIDOREDUKTAZIŲ koenzimai (protein metabolism, etc).

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
see 680 p. (in BIOCHEMISTRY)

ARIBOFLAVINOSIS

ETIOLOGY
n.y. (greičiau susergama, jei vartojama mažai baltymų)

SYMPTOMS & SIGNS

1. Mucosal fissuring - pallor and maceration of mucosa in mouth angles (angular stomatitis) and
vermilion surfaces of lips (cheilosis) → superficial linear fissures → leave scars when healed.

N.B. gerokai dažnesnė angular stomatitis priežastis yra žemi protezai (ar iš viso jų
nedėvėjimas) – lūpų kampai įsiverčia į vidų ir maceruojasi.

2. Seborrheic dermatitis (paraudimai aplink angas - genitalia, face).

3. Rarely, corneal neovascularization and epithelial keratitis.

see 2733 (10a) p.

LABORATORY DIAGNOSIS
Urinary riboflavin↓

Increased activation of RBC glutathione reductase by riboflavin - early sign of deficiency.

Klinika nespecifinė, todėl reikia remtis:

laboratory tests

elimination of other causes

therapeutic trial

TREATMENT

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
Riboflavin 10-30 mg/d until response is evident (minimum 2 sav.)

PYRIDOXINE (VITAMIN B6)

RDA
1.7-2 mg

SOURCES
- įvairus maistas; gausiausiai žarnyno floros sintezuojamas vitaminas!

METABOLISM & FUNCTIONS

 vitamin B6 comprises group of closely related compounds: PYRIDOXINE, PYRIDOXAL, and
PYRIDOXAMINE.

 they are phosphorylated to PYRIDOXAL PHOSPHATE – cofactor for:

A. Nitrogen metabolism - enzymes that use amino acids as substrate (pyridoxal phosphate
prijungia amino acid prie enzimo):

transaminations

deaminations

decarboxylations

racemizations

aldol cleavages

various reactions at β and γ carbons

(pvz. niacino susidarymas iš Trp, hemo sintezė)

B. GLYCOGEN PHOSPHORYLASE (glycogen metabolism)

DEFICIENCY

ETIOLOGY
 PRIMARY DEFICIENCY – rare (most foods contain vitamin B6).

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
 SECONDARY DEFICIENCY - chemical inactivation by drugs (e.g. isoniazid, penicillamine).

 autosomal recessive DEPENDENCY STATES - vit.B6 apoenzimų mutacijos.

SYMPTOMS & SIGNS

1. Skin and mucosa – seborrheic dermatosis, glossitis, etc.

2. CNS – generalized clonic seizures (ypač kūdikiams, maitinamiems rafinuotais mišinukais); in

dependency states, seizures can occur in utero!

 pyridoxine is essential for synthesis of glutamic acid decarboxylase (enzyme for synthesis
of GABA).

 untreated pyridoxine dependency → persistent seizures, uniform severe mental retardation.

3. Peripheral neuropathy (axon loss, sensory > motor).

4. Sideroblastic anemia (pyridoxal phosphate is needed in formation of δ-aminolevulinic acid, rate-

limiting step in heme biosynthesis).

LABORATORY DIAGNOSIS
- whole blood [pyridoxal phosphate]↓

At present, there is no generally accepted test of vitamin B6 status!

 CSF and plasma [pyridoxal-5-phosphate] may be more precise method of confirming diagnosis of
pyridoxine dependency.

PROPHYLAXIS
- vit. B6 skyrimas (100 mg/d) vartojant jam antagonistinius vaistus.

TREATMENT
Underlying causes should be corrected.

Pyridoxine:

deficiency in adults - 50-100 mg/d per os.

dependency - lifelong oral pyridoxine up to 10-600 mg/d.

pyridoxine-dependent seizures – start with 100-200 mg/d IV with simultaneous EEG → seizures
will abruptly cease, and EEG will normalize during next few hours.

N.B. seizures are particularly resistant to anticonvulsants!

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VITAMIN B6 TOXICITY
- pyridoxine megadoses (2-6 g/d for months), mistakenly taken for premenstrual tension.

 very severe sensory neuropathy - propriorecepcijos sutrikimai kojose, sensory ataxia (gali būti
negrįžtama* net nutraukus piridoksino vartojimą!).

*irreversibly damaged dorsal root ganglion cells

RETINOL (VITAMIN A)
RDA
1000 μg (3000 IU) retinol equivalents

1 retinol equivalent = 1 μg retinol = 6 μg β-carotene = 3 IU = 3 USP U

SOURCES
Provitamins (carotenes):

dark green leafy vegetables

yellow vegetables (carrots)

red palm oil

Vitamin A:

1) fish liver oil

2) liver

3) egg yolk

4) fortified milk, margarine

METABOLISM
Vitaminas A yra alkoholis – RETINOL

Vitamino A aldehidas – RETINAL

 maiste randami CAROTENES (s. provitamin A carotenoids) - class of carotenoids.

 carotenes esti trijų rūšių, jiems skylant žarnyne susidaro RETINAL:

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
β-carotene skyla į dvi RETINAL molekules

α-carotene ir γ-carotene duoda tik po vieną RETINAL molekulę.

 žarnyno epiteliocituose:

RETINAL redukuojamas į RETINOL

RETINOL is re-esterified with palmitate (RETINYL PALMITATE – pagrindinė sandėliavimo forma)

ir keliauja į kepenis.

 kepenyse esti 90% vit.A atsargų (as retinyl palmitate).

 kraujyje retinol transportuojamas susijungęs su retinol binding protein.

FUNCTIONS
A. Role in vision:

 in retinal rod cells, retinol oksiduojamas į retinal.

 11-cis RETINAL izomeras jungiasi (as prosthetic group) su scotopsin į regos pigmentą
RHODOPSIN.

 šviesos poveikyje 11-cis retinal virsta į all-trans RETINAL ir generuojamas veikimo potencialas.

smulkiau žr. 3536 p. (in EYE)

B. Kitos funkcijos: in somatic cells, retinol is converted to RETINOIC ACID, which combines with
receptors that bind to DNA and regulate gene expression - regulation of epithelial growth,
reproduction.

 synthetic vitamin analogs (RETINOIDS) are used increasingly in dermatology (globular acne
treatment).

 possible protective role of β-carotene, retinol, and retinoids against some epithelial cancers is
under investigation.

 ISOTRETINOIN (13-cis-retinoic acid) skiriamas nėščioms sukelia malformations

DEFICIENCY

ETIOLOGY
PRIMARY DEFICIENCY - endemic in areas, where rice, devoid of carotene, is staple (southern and
eastern Asia).

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SECONDARY DEFICIENCY:

inadequate conversion of carotene to vitamin A

interference with absorption, storage, or transport of vitamin A.

SYMPTOMS & SIGNS

 pathognomonic changes are confined to eye: see 2733 (13a) p.

1) night blindness (nyctalopia); užsitęsus hipovitaminozei atsiranda negrįžtami struktūriniai

tinklainės pakitimai → aklumas.

2) xerophthalmia → keratomalacia* → ulceracija ir, prisidėjus infekcijai, perforacija →

aklumas. *ragena praranda skaidrumą (reversible on vit. A treatment)

3) BITOT spots (superficial foamy patches composed of epithelial debris and secretions on
bulbar conjunctiva).

 keratinization of lung, GI tract, and urinary tract epithelia, follicular hyperkeratosis of skin.

 gonadal dysfunction in males, miscarriage in females.

 growth retardation in children.

In severe deficiency in children, mortality can be > 50%!

LABORATORY DIAGNOSIS
plasma [retinol] falls after liver stores are exhausted.

trial with therapeutic doses of vitamin A.

PROPHYLAXIS
Xerophthalmia is major cause of blindness among children in most developing countries!

H: prophylactic doses of 66,000 µg (200,000 IU) of vitamin A palmitate in oil orally once
every 3-6 mo for all children aged 1-4 yr; dose is halved for those < 1 yr.

TREATMENT
 oral vitamin A palmitate in oil 20,000 µg (60,000 IU) daily for 2 days and once before discharge
from hospital after 7 to 10 days is usually effective.

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 in presence of vomiting or malabsorption, water-miscible vitamin A must be given IM (oil
preparations are not used IM).

 prolonged daily administration of large doses, especially to infants, must be avoided because
toxicity may result!

During pregnancy and lactation, prophylactic or therapeutic doses should not exceed two
times RDA to avoid possible damage to fetus!

VITAMIN A TOXICITY

ETIOLOGY
1. Massive doses of vitamin A or its metabolites given for globular acne (although treatment is
effective, it puts patient at risk for vitamin A toxicity).

2. Arctic explorers ingesting several million units of vitamin A in polar bear or seal liver.

Excessive ingestion of carotene does not cause vitamin A toxicity (carotene is metabolized to vitamin
A at slow rate) but produces CAROTENEMIA - asymptomatic but may lead to CAROTENOSIS, in which
skin (but not sclera!!!) becomes deep yellow, especially on palms and soles.

SYMPTOMS & SIGNS

Acute toxicity:

1) increased ICP (pseudotumor cerebri): headache and vomiting; may lead to death unless
ingestion is discontinued.

2) rash and peeling of skin

Chronic toxicity:

1) hepatosplenomegaly, ascites

2) bone thickening (cortical hyperostosis)

3) dermatosis

4) birth defects have been reported in children of women receiving 13-cis-retinoic acid
(isotretinoin) for skin conditions during pregnancy!

LABORATORY DIAGNOSIS
- fasting plasma [retinol]↑

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TREATMENT
stopping vitamin A ingestion.

TOCOPHEROL (VITAMIN E)
 VITAMIN E (TOCOPHEROL) - generic term for compounds that have biologic activity of α-
tocopherol.

 vitamin E group contains α-, β-, γ-, and δ-tocopherols.

 d-α-tocopherol is only naturally occurring stereoisomer and most potent (1.49 IU/mg).

 international standard is dl-α-tocopherol acetate (1.0 IU/mg).

RDA
8-10 mg (30 IU)

SOURCES
- vegetables, seed oil.

METABOLISM
- unmetabolized in body; transported in VLDL molecule.

FUNCTIONS
- scavenger of free radicals (i.e. antioxidant) - prevents peroxidation of polyunsaturated fatty acids
in cellular membranes.

DEFICIENCY

ETIOLOGY

INFANTS are born in state of relative vitamin E deficiency (the smaller and more premature infant,
greater degree of deficiency) - limited placental transfer of vitamin E and rapid growth.

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ENDOCRINE SYSTEM, METABOLISM: Vitamins
prophylactic vitamin E may prevent retinopathy of prematurity.

CHILDREN & ADULTS (adults have large vitamin E stores in adipose tissue!):

I. Vit. E transport defects:

1) abetalipoproteinemia (Bassen-Kornzweig syndrome) - mutation of microsomal triglyceride

transfer protein (MTP) see 789 p., Mov50 p.

2) ataxia with isolated vitamin E deficiency (AVED) - 8q13 mutation of α-tocopherol transport
protein (α-TTP) see Mov50 p.

II. Fat malabsorption:

chronic cholestatic diseases

celiac disease

SYMPTOMS & SIGNS

mild hemolytic anemia (esp. in premature infants)

spinocerebellar disease (indistinguishable from classic Friedreich ataxia) see Mov50 p.

reproduction disorders (?) see 2733 (15a) p.

LABORATORY DIAGNOSIS
plasma [tocopherol]↓; varies with total plasma lipid levels, which affect partition between plasma and
adipose tissue, main storage depot for tocopherols (hiperlipidemijos atveju padidėja vitamino E
koncentracija)

peroxide hemolysis↑ (enhanced susceptibility of RBCs to hydrogen peroxide).

creatinuria (on creatine-free diet), necrosis in muscle biopsies.

PROPHYLAXIS
- preventive dose of α-tocopherol (0.5 mg/kg for full-term infants and 5-10 mg/kg for premature
infants).

TREATMENT
 malabsorption – oral α-tocopherol 15-25 mg/kg/d as water-miscible d-α-tocopheryl acetate (1 mg
= 1.4 IU).

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 much larger doses are required to treat neuropathy or to overcome defects of absorption and
transport.

VITAMIN E TOXICITY
 adults have taken large vitamin E amounts (up to 800 mg/d) for years without any apparent harm.

 most significant toxic effect of vitamin E at > 1000 mg/day is antagonism to vitamin K leading to
hemorrhage.

Panaudota literatūra:

R.BERKOW "MERCK Manual", 17 ed., 1999: 4-11, 33-51 p.

NMS Pathology 1993, NMS Biochemistry 1999

SĄS Nr. 17 “Biochemija 1”

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