BIOC 460 DR' TISCHLER LECTURE 29

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BIOC 460 DR. TISCHLER LECTURE 29
CHOLESTEROL STEROIDS
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OBJECTIVES 1. For cholesterol a) list its
physiological functions b) describe its
synthesis c) list 6 groups of hormones produced
from it and their function 2. For bile acids
(salts) a) list their physiological
functions b) describe their synthesis 3. For
the steroid hormones a) identify the five
general classes b) for synthesis of cortisol and
aldosterone identify the tissue where this
occurs outline the general pathways c)
outline the pathway for synthesis of androgens in
the adrenal cortex and in the testes, and
for estrogen in the ovaries and
adipose tissue. 4. Name disorders
associated with vitamin D deficiency 5. Name
disorder associated with estrogen loss
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CHOLESTEROL FACTS

• synthesized from acetyl CoA and eliminated as
  bile acids
• precursor of all other steroids in the body
• product of animal metabolism - in foods of
  animal origin
• amphipathic lipid (hydrophobic and hydrophilic
  portions)
• storage form is cholesterol ester found in
  most tissues.

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CHOLESTEROL FACTS

• essential structural component of membranes
• transported in the circulation in lipoproteins

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ROLES OF CHOLESTEROL AND BILE ACIDS (SALTS)

• The physiological roles of cholesterol include
• an important lipid component of biological
  membranes,
• precursor of steroid hormones and
• source of bile acids.

• Bile acids are polar derivatives of cholesterol
  and aid in
• lipid digestion
• lipid absorption
• cholesterol excretion

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CYTOPLASM
MITOCHONDRIAL MATRIX
Figure 1. Formation of hydroxymethylglutaryl CoA
for the synthesis of cholesterol.
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KEY CYTOPLASMIC REACTIONS ASSOCIATED WITH
CHOLESTEROL SYNTHESIS
citrate lyase citrate ATP CoA ?
oxaloacetate acetyl CoA ADP Pi thiolase
2 acetyl CoA ? acetoacetyl CoA CoA HMG CoA
synthase acetoacetyl CoA acetyl CoA ?
hydroxymethylglutaryl CoA (HMG CoA) CoA
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Figure 2. The four stages of cholesterol
biosynthesis
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Figure 3. The initial reaction, 7?-hydroxylase,
in the conversion of cholesterol to bile acids.

• Rate-determining step
• Repressed (decreased synthesis) by bile salts
• Induced (increased synthesis) by cholesterol

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Table 1. Functions of Hormones Derived from
Cholesterol
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Table 1. Functions of Hormones Derived from
Cholesterol
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Figure 4. General pathways for the synthesis of
aldosterone and cortisol in the adrenal cortex
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Androstenedione
Figure 5. Pathway for formation of androgens in
the adrenal cortex. Beware of the hype about
taking DHEA Cortisol made in same cells as
androstenedione
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In obese men, overproduction of estrogen in fat
cells can cause gynecomastia excessive male
breast development
Figure 6. Pathways for the synthesis of
testosterone (testes) and the estrogens estradiol
(ovaries) and estrone (adipose cells)
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OHase hydroxylase
Specific receptors in intestine, bone,
kidney Ca Intestinal absorption Renal
reabsorption PO4 Intestinal absorption Renal
reabsorption
Figure 7. Photobiosynthesis of vitamin D3 and
its metabolism