Docstoc

Vitamin B6

Document Sample
Vitamin B6 Powered By Docstoc
					Vitamin E, Tocopherol, Factor X



     Vitamins Active in Oxidative
     Metabolism
     Vitamins POSC/NUTR 645
Vitamin E, History
1922, Evans & Bishop, UC Berkeley
   Small yeast or lettuce additions to rat diets

     –Purified contain A,D,C & thiamin
     –Prevent testicular degeneration & pup
       reabsorption
   Designate unknown fertility agent “Factor
    X”
Vitamin E, History

1922-1924, Evans & Bishop
   Factor X present lipid extracts

    –Dried alfalfa, wheat germ, oats, meats &
     milk
    –Single drop of wheat germ oil restores
     fertility
    –Single drop of cod liver oil high in A & D
     did not
Vitamin E, History
1924, Sure, U.Arkansas
   Confirms work of E & B, gives name
    Vitamin E
1932, Olcott and Mattill, U. Iowa
   Oil of wheat germ oil & lettuce

   Potent against pup reabsorption

   Chemical antioxidant measurable in vitro
Vitamin E, History
1936, Evans
   Isolates allophanic acid esters of three
    alcohols from wheat germ oil, one has a
    high bioactivity (potency)
1938, Fernholz
   Proposes vitamin structure of high activity
    alcohol
     –Possesses a phytyl side-chain &
       hydroquinone moiety
Vitamin E, History

1938, Evans coins the term tocopherol
   Greek tokos = childbirth & pherein = to bear

1938, Karrer, Smith & Bergel
   synthesize most active form -tocopherol

   1949, -tocopherol from soybean oil

1959, tocotrienols described
Vitamin E, History
H.M. Evans born in Modesto CA
   Lived to be at least 100, published 1067
    papers
   4.5% miscellaneous topics; 9.5% on
    anatomy; 21% on nutrition & 65% on
    endocrinology
   Evans blue dye is named after him

 Also discovered pituitary growth hormone
Vitamin E, Vitamer Relationships
            R1
     OH               CH3        CH3         CH3
     R2
          R3                                  CH3
Tocopherols:     R1         R2                R3
-tocopherol          CH3              CH3
      CH3
-tocopherol          CH3              H
      CH3
-tocopherol          H                CH3
      CH3
Vitamin EVitamer Relationships
              R1
       OH               CH3   CH3       CH3
       R2
             R3                           CH3

   Tocotrienols:   R1         R2              R3
   -tocotrienol        CH3         CH3
            CH3
   -tocotrienol        CH3         H
            CH3
   -tocotrienol   H          CH3             CH3
   -tocotrienol        H           H
            CH3
Vitamin E, Common Features
              R1
    OH        5        CH3   CH3   CH3
         6
          7        1
    R2        8
          R3           4’    8’    12’ CH3

      6-chromanol

Side-chain derivatives of a ring methylated 6-
 chromanol (3,4-di-hydro-2H-1-benzopyran-6-ol)
Side-chain consists of 3,isoprenoid units (head
 to tail)
Vitamin E, Common Features
               R1
    OH         5        CH3   CH3   CH3
          6
           7        1
     R2        8
           R3           4’    8’    12’ CH3

      6-chromanol
 Free -OH or ester link @ chromanol C-6
 8 stereoisomers -R or S - possible @
  anomeric C-4’, C-8’ & phytyl @ C-2
 Only one occurs naturally - RRR
Vitamin E, Synthetic Forms

Natural source of phytyl side chain
  Only phytyl at C-2 is racemic (R & S)

    –Termed 2RS--tocopherol, (dl- -
     tocopherol)
    –Acetate ester adopted as synthetic
     standard
Vitamin E, Synthetic Forms

Natural source of phytyl side chain
  Commercial synthesis completely chemical

    –Products are racemic - “all-rac”- mixtures
     of all possible steroisomers
    –Acetate esters retain bioactivity
    –Free alcohol used in foods to protect
     product
Vitamin E Vitamer Relationships

1 I.U. Vit.E = 1 mg all-rac--tocopherol
                 Activity relative to   Calculate I.U.
  Compound       RRR--tocopherol
  equivalent
  RRR--tocopherol 100%                       1.35
  -tocopherol         25-50%                 0.67
  -tocopherol         10-35%                 0.14
  tocotrienols         ~30%                   0.40
  all-rac--tocopherol      74%                          1.00
Vitamin E, Chemistry

Light yellow oil at room temperature
Water insoluble
Soluble in nonpolar solvents
Will resonance stabilize e- to become a
 tocopheroxyl radical
   Good quencher of free radicals (e-’s pair)

   Easily oxidized, destroyed by peroxides, ozone
Vitamin E, Chemistry
 Tocopheroxyl radical
   Oxidized by uv light
   Oxidation accelerated by
     –PUFA
     –Free metal ions
 Acid resistant
   Base stable Under anaerobic conditions
 Tocotrienols less heat stable than tocopherols
 Ester forms stable in air
 Fluoresce, 294nm excitation, 330nm emission
Vitamin E, Vitamin Sources
  Synthesized only by plants: plant foods, particularly plant
   oils are richest sources.
     Soy=maize>cotton=palm(tocotrienols)>safflower=peanu
       t>olive>coconut.
     -tocopherol mostly in chloroplasts, other forms in
       different parts of the plants. Green plant better sources
       of tocopherols than yellow. Exist only as free alcohols in
       nature.
     Tocotrienols are found in bran and germ fractions of
       some plants, not green leaves. Exist as esters as well
       as free alcohols.
Vitamin E, Vitamin Sources
 Vegetable oils = 1° dietary source
    Seeds & cereals also contribute
    Wheat germ oil is richest source w/ 0.9 - 1.3 mg/g
     -tocopherol
    Desserts provide most Vitamin in diet
 Processing & food preparation
    Greatly influence a food’s final Vit. E content
      – Oxidizing lipids, drying in sun or air, irradiation,
        canning, milling
    Seasonal fluxuations
Vitamin E, Vitamin Digestion and
Distribution
Absorption: passive micellar diffusion
   bile salts & pancreatic secretions help
   primary site jejunum (medial small intestine)
   absorption inefficient, 35 - 50% absorbed
    Similar to cholesterol
Factors influence bile salt micelle formation will
 affect Vitamin E absorption (Know 2-3, pg 194)
Transported as part of lipoproteins & erythrocytes
Tocopherols Partition Into
Membranes
  Vitamin E, Vitamin Digestion and
  Distribution
 Dietary Fat
      +
 Vitamin E             Liver                     VLDL + IDL
                                                               FFA
                                                                +
Pancreatic Esterases
                                                              Vit. E
    and Lipases

                                LDL
             Bile                      PLTP

                               PLTP          Lipoprotein          Adipose
  Micelle Formation                   HDL2
                                                Lipase
     Absorption
Chylomicron Assembly                            Discoidal HDL
                                LPL
                            FFA                        Muscle
                             +
                           Vit. E
     Gut                                          Peripheral Tissues
Vitamin E, Transport
                     Chylo Remnants
                        
                           IDL
                                 TPP causes
                      
                          LDL       preferential
                      
                           Primary
                       lysosome
                                              secretion of
                     
                                              -tocopherol
                                    
  Bile                 TTP 
                         
                                              as part
                    
Caniliculus          
                      Secondary
                                                of VLDL
                     lysosome
                    Alternate tocopherol forms are
               
                       preferentially lost into bile
Vitamin E, Transport




                     Tissue Vitamin E mg/g
Increases in
 tissue
 concentrations do
 not saturate, but
 become
 increasingly less
 as dose increases                              1      10    100
                                             Dietary Vitamin E mg/Kg Diet
 Vitamin E, Storage Pools

Fast TO or “labile”
 pools
   Plasma & liver
   Rapidly deplete
Slow TO or “fixed”
 pools
   Adipose
   Avail w/ exercise
    not starvation
Tocopherol Binding-proteins
Intracellular transport
   Isolated from several tissues & subcellular
    compartment
   Binding based on lipid structure
     –Similar to retinol/al BPs & PLTP
   Prefer certain isomers
     –RRR > SRR & α > γ
   Genetic defects
Vit. E, Tissue Distribution & Diet Effects

Accumulation rates
   Tissues differ
   Tissues w/ high
    oxidative
    exposure
Dietary lipid &
 oxide content
   Affect the body’s
    storage ability
Vitamin E, Deficiency
Vitamin E, Deficiency

            Gestational Reabsorption




         Control          Vitamin E Deficient
Vitamin E,
                  Animal             Tissue Affected   PUFA Vit. E Se Antiox
 Embryo deg. A    Rat hen turkey     Embryo vessels      Y    Y         Y
 Embryo deg. B    Cow Ewe                                          Y
 Sterility        Rat, GP hamster,   Male gonads              Y
                  dog cock
 Liver Necrosis   Rat pig            liver                     Y   Y
 Fibrosis         Chick mouse        pancreas                      Y
 RBC hemolysis    Rat chick human                       Y      Y         Y
 Anemia           Monkey             Bone marrow               Y         Y
 Encephalomalacia Chick              Cerebellum         Y      Y         Y
Vitamin E Metabolism & Excretion

                                  Other oxidation
α-tocopheroxyl radical               products

           α-tocopheryl hydroquinone

           α-tocopheryl quinone
                                    glucuronates
Vitamin E, Toxicity
Little toxicity
   1000-2000 IU/kg diet no untoward effects
Can antagonize other fat soluble vitamins
   Interfere with absorption
      –reduced mineralization
      –impaired blood clotting
      –reduced hepatic Vitamin A
   Off-compete on binding sites e.g. retinol
   May mimic Vitamin K in tocopherylquinone
    form
What Are Nutrients?
“natural foods contain many compounds that
  have no known nutritional effects. These
  include flavonoids, rutin, quercetin….Some of
  these ….compounds (e.g. caffeine in coffee…
  have pharmacological effects)”
            —U.S. National Research Council’s
          Recommended Dietary Allowances, 1989
Redox Active Compounds

Other Natural          Phytochemical
& Synthetic
•Ascorbate
              Bioflavonoids Non-Flavonoid
•Ubiquinones*
              •Catechins     •Hydroxycinnamic
•PQQ*
              •Tannins       Acids
•Sulfites
              •Anthocyanins •Tocopherols
•BHT
              •Flavonols     •Benzoic Acids
•Thiols
                             •Stilbenes
Flavonoid Bioactivity
     Diet

                                     Peripheral
                                     Tissues
      I
      n
                    Liver
      t
      e
      s
      t
      i      Bile
      n                     Kidney
               Absorption
      e

            Excretion
Metabolism
Phase One
  Catechol - O - Methyltransferase
    –Broad substrate specificity
    –Requires SAM
  Oxidation & Reduction
Phase Two
  Glucuronidation
  Sulfation
Common Metabolism Causes Drug
Interactions   Compounds Involved
                             Naringin,  & its aglycone
Systems Involved             naringenin
   Phase 1 enzymes
                               – Account for ~10% of
      – P450 enzymes             grapefruit juice effect
   Phase 2 enzymes          Furanocoumarins
   P-glycoprotein             – 6',7'-dihydroxy-
    transporter                  bergamottin
      – Located on cell        – geranyloxycoumarin
        surfaces               – 2 others unconfirmed
      – Pump drugs           Sesquiterpene
        (xenobiotics) out
                               – Nootkanone
                             Synergy
Flavonoid Metabolism

                                     OH        3´-methyl
                                          OH



               HO           o


5, 7 glucuronidation            OH
                                               3-methyl
or sulfation           OH



                                          Catechin
Flavonoid
Metabolism
Metabolites in
 Human
 Plasma After
 Ingestion
 of 35 mg Catechin
 within a Wine
 Matrix
Modes of Action
Chemical Antioxidant
Biological Antioxidant
  altered enzyme activities e.g. lipoxygenase
Altered Metabolism
  competition for enzyme systems
     –grapefruit juice & Ca++ channel blockers
     –quercetin, estrogen & SAM
  altered protein synthesis
     –P-gp transmembrane protein & cytotoxin
      efflux
  altered transport(ers)

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:6
posted:7/7/2012
language:
pages:42