Blood Lipids

Triacylglycerides are acted up by pancreatic lipase which gives glycerol, fatty acids mono and diglycerides. The glycerol and short chained (10C & less) fatty acids are absorbed through the intestine wall. Chylomicra are synthesized in the intestine and transport mainly triacylglycerides.

The other blood transport proteins are Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), and High Density Lipoproteins (HDL).

Human Plasma Lipoproteins

STERIODS

Cholesterol
ring D-chain has 8 carbons

Bile Acids ring D has 5 carbons

            cholic acid

Adrenal Hormones ring D has 2 carbons

Progesterone ring D has 2 carbons

produce by corpus luteum and placenta

No'C's also missing methyl group between A & B rings

Estradiol

    No'C's does have the methyl group between A & B rings

Testosterone

Cholesterol has ____________carbons on the side chain.
Bile acids have ____________carbons on the side chain.
Adrenal hormones have _____________carbons on the side chain.
Progesterone has ______________carbons on the side chain.
Sex hormones have ______________carbons on the side chain.

The Pill

Enovid first approved birth control pill in 1960. Injection of progesterone worked, but needed an oral administered hormone. If ingested progesterone would be metabolized. 

They replaced the group on the D ring                     CH₃         with         C/ C
                                                                               |                               |
                                                                              C=O
                                                                               |                              D ring /OH

                                                                            D ring

The pill mimics pregnancy.

"Oral contraceptives may be rendered less effective and increased incidence of break-through bleeding may occur by virtue of drug interaction with: rifampin, isoniazid, ampicillin, neomycin, penicillin V, tetracycline, chloramphenicol, sulfonamides, nitrofurantoin, griseofulvin, barbituates, phenytoin, primidone, phenylbutazone, analgesics, tranquilizers (diazepam), and anti migrane preparations." Check with your pharmacist for possible interactions.

DES - diethylstilbestrol was used to prevent miscarriages in 1950 - 1960's. High incidence of vaginal cancers in daughters of mother's given DES.

RU-486 - Mifepristone

Progesterone is needed to maintain the viability of a fetus. Mifepristone blocks the action of progesterone. Has other uses: slows growth of some cancers, treatment for Cushing syndrome (too much cortisone).

CHOLESTEROL SYNTHESIS

Acetyl CoA units combine to form cholesterol. There is a step in the synthesis whereby an early enzyme is turned off by high cholesterol concentrations. This is called Feed Back Inhibition. The cholesterol molecule then serves to make the other steroids: bile acids, hormones, etc.

The bile acids are reabsorbed from the gut and go to the liver. Some cholesterol lowering drugs work by excreting the bile acids. The bile acids then can't be recyled. New cholesterol molecules would have to be converted to bile acids.

Why do you think dieting is also a part of lowering chlolesterol levels?

KETONE BODIES

When the body uses fatty acids as the primary energy source, three compounds are increased: acetone, acetoacetic acid, and β hydoxybutyric acid. It is a condition known as ketosis. Ketones are built up. The breath smells like Juicy Fruit gum. This is followed by acidosis. The pH of the blood drops.

           O                                           O
      2                                            2
2 H₃C-C-S-Co A ---> CO₂ + H₃C-C-CH₃
        7 
                                              O                                    OH
                       2                                       |
                                    H₃C-C-CH₂-COOH --> H₃C-CH-CH₂-COOH

FATTY ACID SYNTHESIS

Occurs in the cytoplasm
Chain grows 2 carbons at a time from the carboxyl end
The complex splits off a fatty acid after the fatty acid is 14 to 16 carbons long
Uses 2 NADPH*H's for every 2 carbons added
Uses 1 ATP to get it started
The system uses ACP (acyl carrier protein) instead of CoA (Coenzyme A)

Wednesday, March 21, 2007 01:28:02 PM