Bile Acids/Salts & Sterol-derived Molecules

Bile Salts/Acids (Steroid-based Molecules)

synthesized from cholesterol

Cholesterol

is a precursor to steroid hormones, vitamin D, and bile salts

• also present in bile

Bile Salts

• are detergents that render dietary lipids more accessible for digestion by lipases

• synthesized in the liver from cholesterol and stored in the gallbladder until secreted into the small intestine

Excess cholesterol in bile:

may precipitate to form gallbladder stones

Gallbladder Stones

These stones may block bile secretion and inflame the gallbladder

• Symptoms include pain in the upper right abdomen and nausea

• If need be, the gallbladder is removed, and bile flows from the liver through the bile duct directly into the intestine.

Bile

composed of cholesterol, phospholipids, and the breakdown products of heme

Bile acid/salt binding resins:

• Lower cholesterol by removing it from the liver in the form of bile acids/salts

• increase the rate of reverse cholesterol transport

• Drugs: cholestyramine, colestipol

• Dietary fiber lowers cholesterol

Steroid Hormones

• Hormones derived from cholesterol that share a common four-fused-ring structure known as the steroid nucleus

• These hormones are powerful signal molecules that regulate a host of organismal functions

There are five major classes of steroid hormones:

1. Progestagens

2. Glucocorticoids

3. Mineralocorticoids

4. Androgens

5. Estrogens

How do steroid hormones work?

They all function in a similar manner:

They bind to and activate receptor proteins that serve as transcription factors

Transcription Factors

are proteins that regulate the expression of target genes

Progesterone (a Progestagen)

prepares the lining of the uterus for the implantation of an ovum and is essential for the maintenance of pregnancy

Androgens, like testosterone, are responsible for the:

1. development of male secondary sex characteristics,

2. maintenance of the testes, and

3. development of muscle mass

Estrogens such as estradiol:

• are required for the development of female secondary sex characteristics

• along with progesterone, also participates in the ovarian cycle

Glucocorticoids (e.g., cortisol)

1. promote gluconeogenesis and the formation of glycogen,

2. enhance the degradation of fat and protein, and

3. inhibit the inflammatory response

• They enable animals to respond to stress.

• The absence of glucocorticoids can be fatal.

• Mineralocorticoids (primarily aldosterone) act on the kidney to regulate salt balance, volume, and blood pressure.

Mineralocorticoids (primarily aldosterone):

act on the kidney to regulate salt balance, volume, and blood pressure

Androgens can be used to artificially enhance athletic performance:

Some athletes take androgens because the anabolic effects of androgens increase lean muscle mass.

The use of anabolic steroids in people with male reproductive organs often leads to:

1. a decrease in the secretion of testosterone,

2. testicular atrophy, and sometimes

3. breast enlargement (gynecomastia) owing to the conversion of some of the excess androgen into estrogen

In people with female reproductive organs, excess testosterone can cause:

1. a decrease in ovulation and estrogen secretion,

2. breast regression, and

3. the growth of facial hair.

Vitamin D

Is derived from cholesterol by the energy of sunlight:

• The ultraviolet light of sunlight breaks a bond in 7-dehydrocholesterol to form previtamin D3

• This initiates the synthesis of calcitriol (1,25-dihydroxycholecalciferol), the active hormone

Vitamin D Deficiency

• Leads to disease states:

  • This disease in childhood is called rickets

  • This disease in adulthood is called osteomalacia

• People living in northern climes may not be exposed to enough sunlight during certain times of the year to synthesize adequate amounts of vitamin D

• Since skin pigmentation blocks UV radiation, people with dark complexions living in such areas may be especially susceptible to vitamin D deficiency.

  • In the United States, some studies suggest that 75% of people with dark-complected skin have insufficient blood levels of vitamin D.

Rickets

• Characterized by inadequate calcification of cartilage and bone.

• 7-dehydrocholesterol in the skin is not cleaved to previtamin D3 because of little exposure to sunlight for many months and/or diets provided little vitamin D supplementation

Osteomalacia

the softening and weakening of bones

The recommended daily intake of vitamin D:

10 μg, irrespective of age:

• Reliable dietary sources of vitamin D are fortified foods.

• Milk, for example, is fortified to a level of 10 μg per quart.

In muscle and other tissues:

• vitamin D appears to affect a number of biochemical processes, with the net effect being enhanced muscle performance

• prevents cardiovascular disease, reduces the incidence of a variety of cancers, and protects against autoimmune diseases including diabetes

Isopentenyl Pyrophosphate (C5)

• the basic five-carbon building block

• are joined to form a wide variety of biomolecules

• the fragrances of many plants arise from volatile C10 and C15 compounds, which are called terpenes

Myrcene (C10H16)

from bay leaves consists of two isoprene units

Limonene (C10H15)

from lemon oil consists of two isoprene units

Zingiberene (C15H24)

from the oil of ginger, is made up of three isoprene units

Some other terpenes are:

• menthol from peppermint oil

• Citronellal

• Natural rubber is a linear polymer of cis-isoprene units.