FAT SOLUBLE VITAMINS

(VITAMIN E & K)
Muti’ah Mustaqimatusy Syahadah, S.Gz, M.Gz

Prodi S1 Gizi Fakultas Kedokteran

Universitas Diponegoro
Vitamin E (α-tocopherol)
▪ Vitamin E encompasses eight compounds (vitamers)
▪ Two subgroups of vitamin E :
1. Tocopherols (have saturated side ring chains)
2. Tocotrienols (have unsaturated side ring chains)
▪ Each subgroup is composed of 4 vitamers (differ in the number and
location of methyl groups → α, β, γ, and δ)
▪ Cannot be synthesized in the body → must be met from plant foods
▪ RDA 15 mg/day with UL 1000 mg/day
▪ Only α-tocopherol has biologic activity and can meet the body
needs (the others are not converted nor recognized by its transport
protein)
▪ Tocotrienols have 3 double bonds, so it less biologically active
▪ Synthetic forms of α-tocopherol are shown on supplement labels
as DL- or dl-α-tocopherol
▪ Sources of vitamin E :
- Vegetable oils (PUFA plant oils), and its product such as margarine,
salad dressings, mayonnaise
- Wheat germ oil provides significant quantities of vit E
- Nuts, seeds, whole grains, green vegetables, fatty meats
▪ Vit E and PUFA tend to occur together in the same foods
▪ Vit E is susceptible to destruction during food preparation and
storage
▪ Heat and light is significantly reduces vit E content
▪ Vit E also oxidized with lengthy exposure to air
▪ Food processing such as milling can reduce vit E content
Vitamin E Metabolism
▪ Tocopherols are found free in foods, while Tocotrienols are
found esterified (must be hydrolyzed using esterase before absorption)
▪ The metabolic pathway of vitamin E follows fat metabolism
▪ Bile salt assists the free tocopherols in being emulsified to form
micelles
▪ Vit E absorbed in jejunum by passive diffusion
▪ Dietary lipids can improve the vit E absorption up to 70%
▪ In the enterocyte, tocopherols are incorporated into chylomicrons
for transport through the lymph and the into circulation
▪ During transport in the form of chylomicrons, tocopherols is
transferred among lipoproteins especially HDL and LDL mediated
by phospholipid transfer protein
▪ LDL has the highest concentrations of vit E, in which 1 LDL have
5 – 9 molecules of α-tocopherols
▪ Hepatic uptake of vit E occurs following the delivery via
chylomicron remnants
▪ In liver, tocopherols was metabolizes for incorporation into VLDL
▪ VLDL released into the circulation mediated by α-tocopherol
transfer protein (αTTP)
▪ Plasma α-tocopherol concentrations about 5 – 20 mg/L
▪ Deficiency or absence of αTTP leads to vit E deficiency
▪ Those conditions be can caused by NAFLD and metabolic
syndrome and may disrupt the “trafficking” and the use of vit E
▪ The uptake by cells or tissues was mediated by lipoprotein lipase
to hydrolysis chylomicrons and VLDL, and then by phospholipid
transfer protein to facilitate the transfer of vit E from lipoproteins to
cells/tissues
▪ The excretion was by feces or urine which conjugated with
glucuronic acid or sulfate
 Tocopherol Transport Pathway

Lumen Usus Sel Epitel Usus Darah Sel hati

Sistem limfatik
Tokoreril Ester Chylomicron Chylomicron Chylomicron
(TE)

VLDL VLDL

Tokoferol Tokoferol
LDL

Delivery to cells/tissues
Vit E as Antioxidant
▪ The principal function of vit E
▪ Vit E maintains the integrity of membranes and lipoproteins by
protecting cells from oxidation (peroxidation)
▪ Peroxidation occurs in 3 phases:
I. Initiation
II. Propagation
III. Termination → the role of vit E is in this phase
I. Initiation
▪ Free radicals attack organic
molecules such as PUFAs

▪ Alternately, PUFAs can react to

O2 to generate alkyl radicals (L•)
(HO2•)

II. Propagation
▪ L• react with O2 and form lipid
peroxyl radical (LOO•) and
promote peroxidation
III. Termination
▪ Propagation will be stopped when the PUFAs have been completely
attacked (self-quenching) or stopped by antioxidants
▪ Vit E can react with LOO• before they interact with other fatty acids or cells,
provides H for reduction of lipid peroxyl radicals (LOO•)

▪ Vit E also provides a H for reduction of lipid carbon-centered radicals (L•)

▪ After donate the H, vit E becomes oxidized (tocopheroxyl radical)

▪ Then, the tocopherol radical will be regenerated mediated by reducing
agents such as vit C, GSH, NADPH
Protective Against Disease
▪ Heart Disease
Oxidation of LDLs contributes to plaque formation
▪ Cancer
Free radical-induced cell damage can alter in gene expression,
cell growth, dan cell differentiation
▪ Eye Health
Radical-induced cell damage can affect the development of
ocular conditions
Vitamin E Deficiency
▪ Erythrocyte hemolysis (leads to hemolytic anemia)
RBC break and spill their contents → caused by PUFA oxidation
▪ Fibrocystic breast disease (non-malignant breast disease)
▪ Intermittent claudication (abnormality of blood flow → cramp)
▪ Loss muscle coordination and reflexes (neuromuscular
dysfunction)
▪ Impaired vision and speech (neurological symptoms)
Vitamin K
▪ Vitamin K (Danish word “Koagulation” → coagulation or clotting)
▪ Its presence can make the difference between life and death
▪ Vitamin K include phylloquinone (vit K1), menaquinone (vit K2),
and menadione (vit K3)
▪ RDA 65 mcg/day for men and 55 mcg/day for women
▪ Food sources : provided mostly as phylloquinone from plant foods
▪ The main dietary sources include leafy green vegetables
(spinach, turnip green, broccoli) and the second major sources
were vegetable oils and margarine
▪ Exposure to light and heat can significantly destructed vit K
▪ Menaquinones are synthesized by anaerobic bacteria in intestine
(small amounts are found in liver, fish, and fermented product)
▪ Supplements also manufactured in the form of water-soluble
forms (AquaMephyton, Synkayvite, Kappadione) for people with
fat malabsorption disorders
Vitamin K Metabolism
▪ Phylloquinone (K1) is absorbed in jejunum particularly via diffusion
and some may be absorbed by active transport
▪ Menaquinone (K2) is absorbed by passive diffusion in ileum and
colon
▪ Phylloquinone is incorporate into chylomicrons → lymphatic
system → circulatory system → uptake by the tissues
▪ Chylomicron remnants deliver any vit K that not taken up by
tissues to the liver
▪ In liver, phylloquinone was metabolized into MK-4 by removing
the phytyl tail and the production of intermediate menadione
▪ Estimated that 5 – 25% of ingested vit K1 is converted into MK-4
▪ MK-4 then incorporated into VLDL for secretion into circulation
▪ Phylloquinone is the main circulating form in the circulation
▪ Normal concentration range of vit K in blood is 0,2 – 3,2 ng/mL or
0,5 – 6,4 nmol/L
▪ Stored primarily in cell membranes
▪ Phyllo- conjugated with glucuronic acid for excretion in the feces
▪ Menadione → menadiol, reacts with phosphate, sulfate, and
glucuronide and then excreted via feces or urine
Vit K and Blood Clotting
▪ Essential for the activation of several proteins that involved in
blood clotting
▪ Post-translational carboxylation of specific glutamic acid (glutamyl)
residues in proteins to form δ-carboxyglutamic acid (GLA) residues
is assisted by vit K → necessary for blood clotting
▪ The synthesis of vit K-dependent blood-clotting proteins which well-
studied are factor II (prothrombin), factor VII, factor IX, and factor X

Blood clotting cascade

▪ The participation of vitamin K in the carboxylation of proteins is a
cyclic process, often called the vitamin K cycle

https://lpi.oregonstate.edu/mic/vitamins/vitamin-K
▪ Warfarin is an anticoagulant that may be prescribed to people at
risk for thrombotic event (heart attack)
▪ Anticoagulant drugs : warfarin (liver), heparin (circulation), and
aspirin (platelet)
▪ Warfarin inhibits epoxide reductase → impaired carboxylation of
protein → inhibit blood clotting
▪ Heparin increases blood flow → inhibit synthesis of thrombin by
accelerates the synthesis of antithrombin III (it is normal)
▪ Aspirin inhibits the conversion of ARA to thromboxane

Vitamin A and E are known to antagonize vitamin K

Vit K and Bone Health
▪ Vit K-dependent proteins in bone include osteocalcin and matrix
Gla protein (MGP)
▪ These proteins → carboxylated → binds Ca in bone
▪ Osteocalcin : involved in bone remodeling and prevents
overcalcification
▪ Matrix Gla protein : prevents deposition of Ca in blood vessels
and other tissues, promote calcification of bone
▪ Deficiency → osteopenia and fractures
Vitamin K Deficiency
▪ When any of the blood-clotting factors is lacking or deficiency vit K
▪ Genetic disorder such as hemophilia (neither caused nor cured by vit K)
1) The intake and reserve of vit K were low
2) The GI tract is sterile so there are no bacteria for
Hemorrhagic disease the synthesis of vit K
(Often found in newborns) 3) Antibiotic kill the vit K-producing bacteria
4) Anticoagulant drugs interfere with vit K
metabolism
To prevent hemorrhagic disease in the newborn, a single dose of vitamin K
(1 mg phylloquinone) is given at birth
THANK YOU