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8 Focus on Health & Medicine: Cholesterol, the Most Prominent Steroid

8 Focus on Health & Medicine: Cholesterol, the Most Prominent Steroid

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592



LIPIDS



=



HO

cholesterol



Cholesterol is obtained in the diet from a variety of sources, including meat, cheese, butter, and

eggs. Table 19.4 lists the cholesterol content in some foods. While the American Heart Association currently recommends that the daily intake of cholesterol should be less than 300 mg, the

average American diet includes 400–500 mg of cholesterol each day.



PROBLEM 19.21



Why is cholesterol classified as a lipid?



PROBLEM 19.22



(a) Label the rings of the steroid nucleus in cholesterol. (b) Give the number of the carbon to

which the OH group is bonded. (c) Between which two carbons is the double bond located?

(d) Label the polar bonds in cholesterol and explain why it is insoluble in water.



TABLE 19.4

Food



Cholesterol Content in Some Foods

Serving Size



Cholesterol (mg)



Boiled egg



1



225



Cream cheese



1 oz



27



Cheddar cheese



1 oz



19



Butter



3.5 oz



250



Beefsteak



3.5 oz



70



Chicken



3.5 oz



60



Ice cream



3.5 oz



45



Sponge cake



3.5 oz



260



While health experts agree that the amount of cholesterol in the diet should be limited, it is also

now clear that elevated blood cholesterol (serum cholesterol) can lead to coronary artery disease.

It is estimated that only 25% of the cholesterol in the blood comes from dietary sources, with the

remainder synthesized in the liver. High blood cholesterol levels are associated with an increased

risk of developing coronary artery disease, heart attack, and stroke. To understand the relationship between cholesterol and heart disease, we must learn about how cholesterol is transported

through the bloodstream.

Like other lipids, cholesterol is insoluble in the aqueous medium of the blood, since it has only

one polar OH group and many nonpolar C C and C H bonds. In order for it to be transported

from the liver where it is synthesized, to the tissues, cholesterol combines with phospholipids and

proteins to form small water-soluble spherical particles called lipoproteins.



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FOCUS ON HEALTH & MEDICINE: CHOLESTEROL, THE MOST PROMINENT STEROID



593



protein



ester of cholesterol

phospholipid

The surface of the lipoprotein particle

contains polar or ionic groups.

cholesterol

Cholesterol is embedded in the

phospholipid surface, with the nonpolar

carbon skeleton in the interior and the

polar OH group pointing outward.



The interior of the lipoprotein

particle is hydrophobic.

lipoprotein particle



In a lipoprotein, the polar heads of phospholipids and the polar portions of protein molecules are

arranged on the surface. The nonpolar molecules are buried in the interior of the particle. In this

way, the nonpolar material is “dissolved” in an aqueous environment.

Lipoproteins are classified on the basis of their density, with two types being especially important

in determining serum cholesterol levels.

• Low-density lipoproteins (LDLs) transport cholesterol from the liver to the tissues.

• High-density lipoproteins (HDLs) transport cholesterol from the tissues back to the liver.



LDL particles transport cholesterol to tissues where it is incorporated in cell membranes. When

LDLs supply more cholesterol than is needed, LDLs deposit cholesterol on the wall of arteries,

forming plaque (Figure 19.8). Atherosclerosis is a disease that results from the buildup of these

fatty deposits, restricting the flow of blood, increasing blood pressure, and increasing the likelihood of a heart attack or stroke. As a result, LDL cholesterol is often called “bad” cholesterol.





FIGURE 19.8



Plaque Formation in an Artery



a. Open artery



b. Blocked artery



a. Cross-section of a clear artery with no buildup of plaque

b. Artery almost completely blocked by the buildup of plaque



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594



LIPIDS



HDL particles transport excess cholesterol from the tissues back to the liver, where it is converted

to other substances or eliminated. Thus, HDLs reduce the level of serum cholesterol, so HDL

cholesterol is often called “good” cholesterol.

Thus, a physical examination by a physician includes blood work that measures three quantities:

total serum cholesterol, HDL cholesterol, and LDL cholesterol. Current recommendations for

these values and the role of HDLs and LDLs in determining serum cholesterol levels are shown

in Figure 19.9.

Several drugs called statins are now available to reduce the level of cholesterol in the bloodstream. These compounds act by blocking the synthesis of cholesterol at its very early stages.

Two examples include atorvastatin (Lipitor) and simvastatin (Zocor).

HO



O



HO

O



O



F



HO



HO

(CH3)2CH



O



N



O

H

N



C

O



Generic name: atorvastatin

Trade name: Lipitor







Generic name: simvastatin

Trade bame: Zocor



FIGURE 19.9 HDLs, LDLs, and Cholesterol Level



Current recommendations by the National Cholesterol

Education Program:

• Total serum cholesterol: < 200 mg/dL

• HDL cholesterol: > 40 mg/dL



muscles

LDLs



HDLs

liver



• LDL cholesterol: < 100 mg/dL

Cholesterol is synthesized in the liver. High HDL levels are

considered desirable since HDL transports cholesterol back

to the liver. Low LDLs are considered desirable to avoid the

buildup of plaque in the arteries.



cholesterol synthesis



PROBLEM 19.23



Would you expect triacylglycerols to be contained in the interior of a lipoprotein particle or on

the surface with the phospholipids? Explain your choice.



PROBLEM 19.24



Identify the functional groups in (a) atorvastatin; (b) simvastatin.



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STEROID HORMONES



595



19.9 STEROID HORMONES

Many biologically active steroids are hormones secreted by the endocrine glands. A hormone is

a molecule that is synthesized in one part of an organism, which then elicits a response at a

different site. Two important classes of steroid hormones are the sex hormones and the adrenal

cortical steroids.

There are two types of female sex hormones, estrogens and progestins.

OH



HO



HO

estradiol



Estradiol, progesterone, and oral

contraceptives were discussed in

Section 13.5.



O



O



O

estrone



progesterone



• Estradiol and estrone are estrogens synthesized in the ovaries. They control the

development of secondary sex characteristics in females and regulate the menstrual

cycle.

• Progesterone is a progestin often called the “pregnancy hormone.” It is responsible for

the preparation of the uterus for implantation of a fertilized egg.



The male sex hormones are called androgens.

O



OH



HO



O



HEALTH NOTE



testosterone



androsterone



• Testosterone and androsterone are androgens synthesized in the testes. They control the

development of secondary sex characteristics in males—growth of facial hair, increase in

muscle mass, and deepening of the voice.



Some body builders use anabolic

steroids to increase muscle mass.

Long-term or excessive use can

cause many health problems,

including high blood pressure,

liver damage, and cardiovascular

disease.



Synthetic androgen analogues, called anabolic steroids, promote muscle growth. They were first

developed to help individuals whose muscles had atrophied from lack of use following surgery.

They have since come to be used by athletes and body builders, although their use is not permitted

in competitive sports. Many physical and psychological problems result from their prolonged use.

Anabolic steroids, such as stanozolol, nandrolone, and tetrahydrogestrinone have the same effect

on the body as testosterone, but they are more stable, so they are not metabolized as quickly.

Tetrahydrogestrinone (also called THG or The Clear), the performance-enhancing drug used by

track star Marion Jones during the 2000 Sydney Olympics, was considered a “designer steroid”

because it was initially undetected in urine tests for doping. After its chemical structure and properties were determined, it was added to the list of banned anabolic steroids in 2004.

OH



OH



OH



N

N

H

stanozolol



smi26573_ch19.indd 595



O



O

nandrolone



tetrahydrogestrinone



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596



LIPIDS



A second group of steroid hormones includes the adrenal cortical steroids. Three examples of

these hormones are aldosterone, cortisone, and cortisol. All of these compounds are synthesized

in the outer layer of the adrenal gland. Aldosterone regulates blood pressure and volume by

controlling the concentration of Na+ and K+ in body fluids. Cortisone and cortisol serve as antiinflammatory agents and they regulate carbohydrate metabolism.



cortex

right

adrenal

gland



medulla



kidney

O

HO



CHO



O

CH2OH

O



O



HO



OH



CH2OH

OH



O



O

aldosterone



O



CH2OH



cortisol



cortisone



Cortisone and related compounds are used to suppress organ rejection after transplant surgery

and to treat many allergic and autoimmune disorders. Prolonged use of these steroids can have

undesired side effects, including bone loss and high blood pressure. Prednisone, a widely used

synthetic alternative, has similar anti-inflammatory properties but can be taken orally.

O

O



CH2OH

OH



O

prednisone

(synthetic steroid)



PROBLEM 19.25



Compare the structures of estrone and progesterone. (a) Identify the differences in the A ring of

these hormones. (b) How do these hormones differ in functionality at C17?



PROBLEM 19.26



Point out three structural differences between the female sex hormone estrone and the male sex

hormone androsterone.



PROBLEM 19.27



Identify the functional groups in aldosterone. Classify each alcohol as 1°, 2°, or 3°.



PROBLEM 19.28



The male sex hormone testosterone and the anabolic steroid nandrolone have very similar

structures and, as you might expect, similar biological activity. Point out the single structural

difference in these two compounds.



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FOCUS ON HEALTH & MEDICINE: FAT-SOLUBLE VITAMINS



597



19.10 FOCUS ON HEALTH & MEDICINE

FAT-SOLUBLE VITAMINS

Vitamins are organic compounds required in small quantities for normal metabolism

(Section 11.7). Since our cells cannot synthesize these compounds, they must be obtained in the

diet. Vitamins can be categorized as fat soluble or water soluble. The fat-soluble vitamins are

lipids.

The four fat-soluble vitamins—A, D, E, and K—are found in fruits and vegetables, fish, liver,

and dairy products. Although fat-soluble vitamins must be obtained from the diet, they do not

have to be ingested every day. Excess vitamins are stored in adipose cells, and then used when

needed. Table 19.5 summarizes the dietary sources and recommended daily intake of the fatsoluble vitamins.



TABLE 19.5

Vitamin



Fat-Soluble Vitamins

Food Source



Recommended Daily Intake



A



Liver, kidney, oily fish, dairy products, eggs,

fortified breakfast cereals



900 µg (men)

700 µg (women)



D



Fortified milk and breakfast cereals



E



Sunflower and safflower oils, nuts, beans,

whole grains, leafy greens



K



Cauliflower, soybeans, broccoli, leafy greens,

green tea



5 µg

15 mg

120 µg (men)

90 µg (women)



Source: Data from Harvard School of Public Health.



Vitamin A (Section 11.7) is obtained from liver, oily fish, and dairy products, and is synthesized

from β-carotene, the orange pigment in carrots. In the body, vitamin A is converted to 11-cisretinal, the light-sensitive compound responsible for vision in all vertebrates (Section 16.7). It is

also needed for healthy mucous membranes. A deficiency of vitamin A causes night blindness,

as well as dry eyes and skin.

CH3



H

C

C

H

CH3

CH3



CH3



H



C



C



CH3

C



C



C



C



H



H



H



CH2OH



vitamin A



Vitamin D, strictly speaking, is not a vitamin because it can be synthesized in the body from

cholesterol. Nevertheless, it is classified as such, and many foods (particularly milk) are fortified

with vitamin D so that we get enough of this vital nutrient. Vitamin D helps regulate both calcium

and phosphorus metabolism. A deficiency of vitamin D causes rickets, a bone disease characterized by knock-knees, spinal curvature, and other skeletal deformities.



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598



LIPIDS



CH3



CH(CH3)(CH2)3CH(CH3)2



H

C



C

H

CH2



HO



vitamin D



Vitamin E is an antioxidant, and in this way it protects unsaturated side chains in fatty acids from

unwanted oxidation (Section 13.12). A deficiency of vitamin E causes numerous neurological

problems, although it is rare for vitamin E deficiency to occur.

CH3

HO

(CH2)3CH(CH2)3CH(CH2)3CH(CH3)2

O



CH3



CH3



CH3



CH3



CH3



vitamin E



Vitamin K regulates the synthesis of prothrombin and other proteins needed for blood to clot.

A severe deficiency of vitamin K leads to excessive and sometimes fatal bleeding because of

inadequate blood clotting.

CH3



O

CH2



CH3

O



smi26573_ch19.indd 598



C

C

H



(CH2)3CH(CH2)3CH(CH2)3CH(CH3)2

CH3



CH3



vitamin K



12/16/08 11:26:16 AM



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