Biosynthesis of Steroids from Squalene

Document Sample
Biosynthesis of Steroids from Squalene Powered By Docstoc
					    Lipids
  Broadly defined as
 naturally occurring non-
polar compounds having
simple functional groups.
Major Categories of Lipids

   Fats and Oils
     • Biosynthesis of fatty acids
   Phospholipids
   Waxes
   Terpenes
   Steroids
   Prostaglandins
Fats

   Esters of fatty (long chain carboxylic) acids
   Common are triacyl glycerols, which can be
    hydrolyzed (saponified) into soaps:
          O
     CH2OC
         O
      CH2O2C
     CHOC
      CHOO2C
                                                                     aq. NaOH
      CH2O2
     CH2OC C


        CH2OH                      Soap (mixture of salts of fatty acids):
        CHOH    +   C13H27CO2 Na   +   C15H31CO2 Na          +   C17H35CO2 Na
        CH2OH
  Micelles: mode of action of soap

    Na O

           O



  Soap (above) can be represented as:                 H2O                  H2O
                                                                      P   P   P
                                                                                      H2O
                                                                  P               P
               P                                H2O           P                       P
                                                          P                               P
                                                      P                                       P
Soap (and detergents) form spherical clusters         P                                       P
(right) called micelles; micelles surround      H2O   P                   Oil                 P
and dissolve non-polar substances (oily                   P                               P
stains) and render them “soluble.”              H2O           P
                                                                  P               P
                                                                                      P
                                                                      P   P   P
 Oils (polyunsaturated fats)




                                    O
                               CH2OC
                           O
                           CO CH
                                   O
                               CH2OC



Presence of cis double bonds in oils makes it difficult
for the molecules to pack regularly in a solid structure;
oils have lower melting points than fats, and are liquids at RT.
Biosynthesis of Fatty Acids

    Repetitive applications of thio-Claisen
   reactions; explains why most fatty acids
    have an even number of carbon atoms
Enolization / Carboxylation
of Acetyl Coenzyme A
                                       H
              O                    O
      CH3CSCoA               CH2=CSCoA
  (acetyl CoA, a 2 C unit)    (enol form)


              O       H
  +       C       O            O       O
  H   O
          CH2=CSCoA          HOCCH2CSCoA
                             (malonyl CoA)
Acylation of Malonyl Coenzyme A
with 2 Carbon unit

                               O
                             CH3C    S synthase

                                                  H
  O    O                              O     O
HOCCH2CSCoA                         HOCCH=CSCoA
(malonyl CoA)
                  O      O                  Enol form
                CH3CCHCSCoA
                     C
                HO       O
Decarboxylation, Reduction,
Dehydration and Reduction
         O       O                O     O
                     -CO2
     CH3CCHCSCoA                CH3CCH2CSCoA
           C
                 O                      [H] (NADPH)
      HO

                                   OH       O
                                CH3CHCH2CSCoA

                                        -H2O
             O                              O
                       [H]
CH3CH2CH2CSCoA                  CH3CH=CHCSCoA
                      (NADPH)
 (a 4 Carbon unit)
Acylation of Malonyl Co A
with 4 carbon unit
                                   O
                     CH3CH2CH2C          S synthase

                   (4 carbon unit)                    H
    O     O                              O      O
  HOCCH2CSCoA                          HOCCH=CSCoA
   (malonyl CoA)
                             O     O
                   CH3CH2CH2CCHCSCoA
                               C
                          HO         O
Conversion to 6 carbon unit


          O      O          decarboxylation,
  CH3CH2CH2CCHCSCoA         reduction of C=O
                            dehydration
             C              reduction of C=C
        HO       O


                                 O
             CH3CH2CH2CH2CH2CSCoA



                     (6 carbon unit)
Acylation of Malonyl Co A
with 6 carbon unit
                                  O
             CH3CH2CH2CH2CH2C          S synthase
                                                    H
        O     O (6 carbon unit)           O   O
     HOCCH2CSCoA                      HOCCH=CSCoA
   (malonyl CoA)

                                  O       O
               CH3CH2CH2CH2CH2CCHCSCoA
                                      C
                              HO          O
Conversion to 8 carbon
unit...etc.

                 O   O   decarboxylation,
                         reduction of C=O
 CH3CH2CH2CH2CH2CCHCSCoA
                         dehydration,
                 C       reduction of C=C
              HO   O

                                       O
              CH3CH2CH2CH2CH2CH2CH2CSCoA


                          (8 carbon unit)
Common Saturated Fatty Acids

                            CO2H
        C14 Myristic Acid



                                   CO2H
        C16 Palmitic Acid



                                          CO2H
        C18 Stearic Acid
Common Unsaturated Fatty Acids
                        O
                        C
                            OH
          Palmitoleic
                        O
                        C
                            OH
          Oleic
                        O
                        C
                            OH

          Linoleic
 Polyunsaturated Fatty Acids
Polyunsaturated fatty acids (PUFAs) include those having two
and three double bonds.

Omega-3 fatty acids are those unsaturated fatty acids that have
a double bond between the third and fourth carbon from the end
of the carbon chain (opposite the CO2H group).

A common omega-3 fatty acid found in fish oil is linolenic acid:

               3            9
                                                    O
       1            6
                                                    C
                                                        OH
           2

Omega-3 fatty acids are considered beneficial for brain function.
  Composition of Fats and Oils
                 lauric   myristic   palmitic stearic   oleic linoleic
                   C12      C14       C16       C18     C18(1)   C18(2)
Animal Fats
Lard               -        1         25        8       50       10
Beef Fat           -         -        27       14       50        3
Butter Fat         2        10        29       10       27        5
Human Fat          1        3         25        8       46       10
Whale Blubber      -        8         12        3       35       10
Vegetable Oils
Coconut oil       48        18        11         2       7        1
Corn oil           -        1         10         3      45       35
Olive oil          -        1          7         3      82        6
Peanut oil         -        -          7         5      58       24
Soybean oil        -        -         10         2      29       51
  Fats and Oils in Nuts

  Nut   g. prot./oz.   g. fat/oz   % sat’d   % MUFAs   % PUFAs
Walnuts       4            18        10         15        75
Almonds       6            14        10         65        25
Hazelnuts     4            17         9         77        14
Cashews       4            13        21         62        17
Macadamia     2            22        16         76         8
Pecans        3            20         9         53        28
Peanuts       7            14        16         52        32
Phospholipids
   Phospholipids are long-chain fatty esters of
    glycerol also containing a phosphoric acid
    derivative.
   They contain a glycerol backbone, like fats and
    oils, but they have a phosphate group with an
    ionic alkyl ammonium group also attached.
Representative Phospholipids
                 O                                          O
      O   CH2O C     R                       O      CH2O C      R
 R'   C O C H    O                     R'    C O C H        O
          CH2O   P   O CH2CH2N(CH3)3                CH2O    P   O CH2CH2NH3
                 O                                          O

Phosphatidylcholine                    Phosphatidylethanolamine
    (lecithin)                          O
                                           (cephalin)
                                        C O CH2
                                        O
                                            C O C   H
                                                        O
                                                 CH2O P     O CH2CH2N(CH3)3
                                                        O
Phospholipids…
                        O
                        C O CH2
                        O
                        C O C   H
                                    O
                              CH2O P    O CH2CH2N(CH3)3
                                    O

     Can be represented as:



                                  P
Lipid Bilayer of Cell Membranes

       Outside the cell (aqueous)
          P   P   P   P   P   P   P




                                      Cell membrane


          P   P   P   P   P   P   P

        Inside the cell (aqueous)
Waxes

   Long chain esters of long chain fatty acids

                          Waxes:

              CH3(CH2)mCO2(CH2)nCH3

               m = 8 - 18      n = 15 - 35


                      O
                  O


                 (present in beeswax)
Terpenes

   Derived biosynthetically from a branched five
    carbon unit, isopentenyl pyrophosphate:


                       O       O
                       P       P
                   O       O       O
                        O     O
        isopentyl pyrophosphate
       isopentenylpyrophosphate        isoprene
Terpenes...

   Common monoterpenes (C10):

                    OH



         CH2OH                      OH

                         CHO
         geraniol                  menthol
                          citral
Some more common terpenes
            O

                 H




             O

                 H




                                       zingiberene
 citronellal           limonene         (ginger)
 (oil of citronella)   (lemons)   a sesquiterpene; 15 Cs
Steroids

   Involved in regulatory processes and in sexual
    characteristics and functions
   Common steroids include cholesterol, estradiol,
    testosterone, estrone and progesterone
              CH3   R
                                           CH3
    CH3   C    D             CH3                 R
                                       C
A     B                                    D
                        A          B
Some Common Steroids
                    CH3OH                         CH3 O
                         H
        CH3     H                   CH3       H

            H       H                   H         H
  O                          HO
         testosterone               androsterone

                    CH3 O
                                                  CH3 OH
                H
                                              H
            H       H
                                        H         H
 HO
                             HO
      estrone
                                  estradiol
…More Common Steroids
                            OH
                          CH3 C CH                                  OH
                                                                  CH3 C CH
                     H
                                                    H         H
                H         H
                                                        H         H
 HO
                                            O
        ethynylestradiol                          norethrindrone

                             O   CH3
                         CH3 C
                                                              CH3
                                                                      H
          CH3       H
                                                CH3     H
             H           H
                                                    H         H
 O
                                       HO
      progesterone
                                                cholesterol
…More Common Steroids


                     O   CH2OH
                                              OH                CO2H
                 CH3 C                             CH3
     O                   OH                                 H
     CH3     H                        CH3     H

         H       H                        H        H
 O                               HO              OH
     cortisone                        H       cholic acid
Prostaglandins
   C20 carboxylic acids that contain a 5-member
    ring and have two long side chains.

   They were first isolated from prostate glands of
    sheep, but now they are known to have
    widespread distribution among tissues, and to
    exhibit an extraordinarily wide range of biological
    effects.
Representative Structures

                                 CO2H
                                             Biosynthetic source:
                                             arachidonic acid

     O       H                     HO H H
                          CO2H
                                                           CO2H

HO                                 HO
         H       HO   H                  H     HO   H

Prostaglandin E1 (PGE1)                 Prostaglandin F2a (PGF2a)
    Some Varied Biological
    Effects of Prostaglandins
   Lower blood pressure
   Affect clotting of blood
   Lower gastric secretions
   Promote inflammation (countered by aspirin,
    which inhibits PG biosynthesis)
   Affect reproductive systems
   Stimulate uterine contractions during childbirth
Final Exam

Review:
 A review session is scheduled for class on
 Wednesday, December 2.

Final Exam: (Dobo Hall, Room 205)

9 am class: Friday, December 4, 8:00 am – 11:00 am
1 pm class: Monday, December 7, 11:30 am – 2:30 pm

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:12
posted:3/1/2010
language:English
pages:34