FAT SOLUBLE VITAMINS

BY

BRIG ABDUL KHALIQ NAVEED

DEAN, PROF & HEAD DEPT OF
BIOCHEMISTRY & MOLECULAR
BIOLOGY
LIPID SOLUBLE VITAMINS

C H3

H2 C

C
C
H
CH2
 LIPID SOLUBLE VITAMINS
• ABSORBED ALONG WITH FATS/LIPIDS
• TPT ALONG WITH LIPOPROTEINS OR SPECIFIC
BINDING PROTEINS
• VIT A-RETINOIDS FOR NIGHT VISION AND
EPITHELIAS
• VIT D FOR Ca & P - METABOLISM
• VIT E-ANTIOXIDANTS PROTECT LIPID
PEROXIDATION
• VIT K-BLOOD CLOTTING, POST
TRANSLATIONAL MODIFICATION OF
CLOTHING FACTORS; II, VII, IX, & X
 FAT SOLUBLE VITAMINS
• THE LIPID SOL (FATE SOLUBLE) VIT ARE
APOLAR HYDROPHOBIC MOLECULES WHICH
ARE ALL ISOPRENOID DERIVATIVES EXCEPT
VIT-D WHICH IS STEROL DERIVATIVE.
• ABSORBED BY GIT LIKE FATS SO FATS
SHOULD BE ABSORBED NORMALLY
• “STEATORRHOEA AND BILIARY DISORDERS”
WILL DISTURB FAT ABSORPTION SO LEAD TO
MALABSORBTION OF THESE VITAMINS
• TRANSPORTED IN BLOOD BY LIPOPROTEINS
OR SPECIFIC BINDING PROTEINS.
 FAT SOLUBLE VITAMINS
• STORED IN LIVER (VIT A, D,K). VIT-E IS STORED IN
ADIPOSE TISSUE
• NOT EXCRETED IN URINE BUT VIA BILE AND THUS
EXCRETED VIA FECES. BUT ONLY WATER
SOLUBLE VARIANT
• BECAUSE BODY CAN STORE EXCESS VIT SO
TOXICITY CAN RESULT DUE TO OVER DOSAGE
ESPECIALLY FOR VIT-A AND VIT-D (1,25 DIOH-D3)
• IN TRUE SENSE VIT-D (CHOLECALCIFEROL) IS A
HORMONE INTIMATELY INVOLVED IN
REGULATION OF Ca++ AND PHOSPHATE
METABOLISM [CALCITRIOL]
 FUNCTIONS OF VITAMIN A
(RETINOIDS)
• SUPPORT GROWTH AND HEALTH
• VISION (ROD-VISION) - RETINAL
• REPRODUCTION - RETINOL
• MUCOUS SECRETIONS AND
EPITHELIAS (RETINOID ACID)
 VITAMIN A (RETINOL)
(RETINOIDS)
• SOURCE: RETINOL FROM FOODS OF ANIMAL
ORIGIN. LIVER, OILS OF FISH ARE RICHEST
SOURCE IN FOOD. MILK, BUTTER, EGG YOLK,
LIVER, HEAT STABLE
• RETINAL, RETINOIC ACID AND RETINOL
EXHIBIT BIOLOGICAL ACTIVITY OF VIT A
• ONLY RETINOL HAS FULL “VIT A” ACTIVITY
• VIT A HAS A PROVITAMIN ( CAROTENE IN
VEGETABLE CARROT (1/6 EFFECTIVE AS VIT-
A) DARK GREEN VEGETABLE & FRUITS,
YELLOW
 RETINOIC ACID
 PARTICIPATE IN GLYCOPROTEIN SYNTHESIS
 PHOSPHORYLATED RETINOIC ACID ACT AS
CARRIER OF SPECIFIC OLIGOSACCHARIDES
RESIDUES. TO FORM GLYCOPROTEINS;
 DEFICIENCY OF THIS MOITY CAUSE
REDUCTION OF 80% MANNOSE BOUND TO
LIVE GLYCOPROTEINS
 RETINOIC ACID; PARTICIPATE IN
GLYCOPROTEIN SYNTHESIS THIS ACTION OF
RETINOIC ACID IS FOR PROMOTING GROWTH
AND DIFFERENTIATION OF TISSUE
RETINOIC ACID; PARTICIPATE IN
GLYCOPROTEIN SYNTHESIS THIS
ACTION OF RETINOIC ACID IS FOR
PROMOTING GROWTH AND
DIFFERENTIATION OF TISSUE
 ABSORPTION, TPT &
METABOLISM OF VIT.A
• DIGESTION OF VIT A ACCOMPANIES THAT OF
LIPIDS FOLLOWED BY TRANSFORMATIONS
IN THE INTESTINAL MUCOSA
• RETINOL ESTERS IN DIET ABSORBED IN
INTESTINE
• ß-CAROTENE RETINAL
RETINOL + RETINOIL ACID IN CELL
RETINOL ESTERS CHYLOMICRONS
LIVER
 FUNCTIONS
• RETINOL ACTS LIKE A STEROID
HORMONE
• RETINOL CRBP+ NUCLEAR PROTEIN
CONTROL OF EXPRESSION OF
GENES. SUPPORT OF THE
REPRODUCTIVE SYSTEM MAY BE
ASCRIBED TO THIS FUNCTION
 ß - ( CAROTENE
DIOXYGENASE
ß-( CAROTENE RETINALDEHYDE
O2
BILE SALTS (TWO MOLECULES
LECITHIN

REDUCTASE
RETINALDIHYDE RETINOL (VIT A)

NADPH NADP+

OXIDIZED

(RETINOIC ACID)
 VITAMIN A IS STORED IN LIVER AND
RELEASED INTO BLOOD ATTACHED TO
BINDING PROTEINS

• RETINOL BINDING PROTEIN (RBP) [APORETINOL

BINDING PROTEINS]
• CELLULAR RETINOL BINDING PROTEIN (CRBP) (IN
CYTOPLASM OF CELL)
• RETINOL, RETINAL AND RETINOIL ACID EACH
HAVE THEIR OWN UNIQUE BIOLOGIC FUNCTION
• RETINOL RETINAL
• RETINOIC ACID ONCE FORMED CAN NOT BE
RECONVERTED BACK TO RETINAL OR RETINOL
 VIT A ROLE IN DIM VISION (NIGHT VISION) [RETINAL] VIT A

RHODOPSIN

DARK LIGHT

OPSIN
11-CIS RETINAL ALL-TRANS RETINAL
ISOMERASE

NADH NADH

ALCOHOL DEHYDROGENASE

NAD NAD

11-CIS RETINOL ALL TRANS RETINOL

ISOMERASE
 DEFICIENCY SYMPTOMS
LACK OF VITAMIN A CAUSES CHARACTERISTIC
DEFICIENCY SYMPTOMS. THESE ARE DUE TO
MALFUNCTION OF THE VARIOUS CELLULAR
MECHANISMS IN WHICH RETINOIDS PARTICIPATE
 DEFECTIVE NIGHT VISION – NIGHT BLINDNESS
[RETINAL]
 KERATINIZATION OF OF TISSUES OF EPITHELIALS
OF EYES, LUNGS, G.URI, TRACT WITH REDUCTION
IN MUCOUS SECRETIONS [RETINOIC ACID]
[RETINOL]
 XEROPHTHALMIA AND KERATOMALACIA
 BOTH RETINOIDS AND CAROTENOIDS HAVE
ANTICANCER ACTIVITY BY VIRTUE OF THEIR
ANTIOXIDATION PROPERTY
 DEFICIENCY SYMPTOMS
 RETINOID FOR NORMAL CELL DIFFERENENTIATION
 RETINOIDS DECREASED EFFECT OF SOME
CARCINOGENS
 BETA CAROTENE IS AN ANTIOXIDANT
IT TRAPES PEROXY – FREE RADICALS IN TISSUES AT
LOW PARTIAL PRESSURE OF O2
 VIT E HAS THIS PROPERTY AT HIGH O2 CONC
THESE TWO LIPID SOL VITAMINS MAY WELL
ACCOUNT FOR THEIR POSSIBLE ANTICANCER
ACTIVITY, IN CONJUCTION WITH ASCORBIC ACID,
WHICH REDUCES TH OXIDIZED FORM OF VIT E, TO
BE UTILIZED AS ANTIOXIDANT
 VIT A DEFICIENCY

• DEFECTIVE NIGHT VISION-WHEN LIVER

STORES ARE NEARLY EXHASTED
• KERATINIZATION OF EPITHELIUM OF EYES,
LUNGS, GIT, GENIT URINARY TRACT
• REDUCTION IN MUCOUS SECRETIONS
• XEROOPHTHALMIA
• KERATOMALACIA
• POOR DIET, ALCOHOLICS
 VIT A TOXICITY
• OCCURS WHEN CAPACITY OF CRBP HAS BEEN EXCEEDED
• EXCESSIVE USE OF VIT-A SUPPLEMENT
• ARCTIC EXPLORER CONSUMING POLAR BEAR LIVER
ACUTE;
 HEADACHE, NAUREA, VOMITTING,
 BONE PAIN, PELLING SKIN
CHRONIC
 ANOREXIA, DRY ITCHING SKIN,
 ALOPECIA, HEPATOSPLECNOMEGALY
 ANAEMIA,
 BLEEDING
 FULL SYNDROME OF DEFICIENCY

• NIGHT BLINDNESS
• XERODERMA
• XEROPHTHALMIA (BITOT,S SPOTS)
• KERATOMALACIA
• SEVERE GROWTH ( ↓ ) NERVOUS SYSTEM
• GLANDULAR DEGENERATION
 Effects of atRA (Renova)
on photoaged skin
18 months topical treatment once daily

before after
C.N. Ellis, et al., J. Amer. Acad. Dermatology 23, 629-637 (1990).
 Effects of retinoic acid on
human skin

protective -RA +RA

barrier

epidermis

dermis
Retinoids and cystic acne

before after RA
Systemic dosing of RA and
cystic acne

before after RA
Severe Darier’s disease

before after
Retinoids and psoriasis
vulgaris

before after RA