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Steroid Hormone Synthesis

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63 views22 pages

Steroid Hormone Synthesis

Uploaded by

Robert Simazuo
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Steroid Hormone Synthesis

Dr. Rehana Omar


School of Medicine
Department of physiological sciences.
[email protected]
Objective of this session

Illustrate the common origin of steroid hormones and


how subtle differences in the position of functional
groups results in functional diversity of the hormones
HORMONES
➢ Play important role in regulating almost every process in an
organism.
Some hormonally regulated events include;
1. Blood pressure
2. Electrolyte balance
3. Sexual differentiation
4. Development, reproduction
5. Digestion, hunger, eating behavior,
6. Metabolism
They can be classified according to the type of hormone they are
e.g. peptide hormones and steroid hormones
DIVERSITY OF HORMONES
➢ Can be classified on basis of how they are
transported to target cells.
➢ Endocrine = hormones released in blood and travel
this way to target cells (e.g. insulin and glucagon).

➢ Paracrine= Hormones that act on cells in vicinity of


their release-(eicosanoids).

➢ Autocrine = Hormones that effect the same cell that


releases it.
HORMONES AND THEIR MODES OF ACTION

Lehninger Principles of Biochemistry, Fourth Edition


Steroid Hormones
➢ Derived from cholesterol.
➢ They move through blood on protein carriers to target tissue
(bind to specific cell surface receptors).
➢ Steroid hormones are produced in the female (ovaries and
placenta) and male (testes)
➢ Steroid hormones produced in the adrenal cortex such as
cortisol and aldosterone (regulate glucose metabolism and
salt excretion respectively).
➢ Prednisolone and prednisone are synthetic mimics of
steroids-anti inflammatory chemicals.
Steroid Hormones
Steroid hormones produced in the adrenal cortex are;

1. Mineralcorticoids (control reabsorption of inorganic ions (sodium, chloride


and bicarbonate) by the kidney
2. Glucocorticoids (which regulate gluconeogensis and reduce inflammatory
responses)

Sex hormones are produced in the male and female gonads as well
as the placenta. Examples are;

1. Progesterone (regulates the female reproductive cycle)


2. Androgens- testosterone and estrogen (which regulate sexual development
in males and females respectively)

Because hormones are effective at low levels, they are synthesized in


small quantities however this is highly regulated to ensure proper
development.
Steroid Hormones
Common structure with four fused planar rings

Lehninger Principles of Biochemistry, Fourth Edition


Steroid hormone synthesis
Even though cholesterol is associated with cardiovascular disease, it
is essential as a component of the cell membrane and is involved in
synthesis of steroid hormones

It is easily synthesised in our cells in a 4 step process;

1. 3 acetate molecules condensed to make the 6 carbon molecule


mevalonate
2. Mevalonate is converted into an activated isoprene units
3. Six 5 carbon isoprene units are polymerised to form a 30 carbon
linear squalene
4. This linear structure is cyclized to form a ring structure (steroid
nucleus) and undergoes a few molecular changes to form
cholesterol
Lehninger Principles of Biochemistry, Fourth Edition
The details of cholesterol synthesis
Step 1: condensation of 2 molecules of acetyl
CoA to form acetoactyl CoA ( by thiolase)

Ccondensation with a third acetyl CoA


molecule to form HMG-CoA (by HMG CoA
synthetase)

HMG-CoA reductase that converts HMG-CoA


to mevalonate.

This stage is a rate limiting reaction regulated


by the ER integral enzyme.

This process uses up 2 NADPH molecules ie


energetically expensive

Lehninger Principles of Biochemistry, Fourth Edition


The details of cholesterol synthesis
Step 2: Phosphate groups from 3 ATP
molecules are added to mevalonate
converting it into activated isoprenes.

Lehninger Principles of Biochemistry, Fourth Edition


Step 3: Head to tail
condensation of six activated
isoprenes to form the
linearised squalene molecule.

Lehninger Principles of Biochemistry, Fourth Edition


The details of cholesterol synthesis

Finally, monooxygenase
enzyme adds oxygen to the
end of the squalene chain.

In animals, lanosterol is
formed. This contains the 4
fused rings typical of
cholesterol (i.e. the ring
nucleus).

Lanosterol in converted to
cholesterol through up to
20 reactions

Lehninger Principles of Biochemistry, Fourth Edition


Uses of cholesterol
➢ Cholesterol serves many purposes e.g. can be
used to make bile, membrane synthesis and a
precursor for steroid hormones and vitamin D

➢ It is carried through the blood as plasma


lipoproteins (remember lipids are insoluble in
water and therefore need special ways to be
transported via blood to wherever they are
needed)

➢ These particles can be of various densities


ranging from chylomicrons to high density
lipoproteins
Lehninger Principles of Biochemistry, Fourth Edition
Synthesis of steroid hormones from cholesterol

Synthesis requires the removal of


carbon (happens in the mitochondria of
tissues that make steroid hormones).

Hydroxylation and oxygenation


reactions are catalyzed by mixed
function oxidase enzymes coupled to
NADPH

Oxygen or mitochondrial cytochrome p-


450 (this is just a carrier for group
exchanges to happen)

The molecule is then re-structured into


the precursor pregnenolone from which
other steroid hormones arise

Lehninger Principles of Biochemistry, Fourth Edition


Schematic of some hormones derived from cholesterol

Lehninger Principles of Biochemistry, Fourth Edition


Hormone related disorders: Women
Hirsutism: Excessive hair growth (face, abdomen, back)
Increased production of male hormones
Maybe a sign of adrenal/ovarian tumors

Turner Syndrome: 1 X chromosome


completely or partly missing.

Results in many systemic disorders (e.g. cardiac,


renal, reproductive, lymphatic)

Treatment: hormone replacement therapy


Hormone related disorders: Men

2 or more X chromosomes in males


(normal:XY Abnormal: XXY)

Low muscle tone, breast growth, less


hair, poor coordination, speech
impairment, difficulty reading

Treatment: begin testosterone at


puberty
Dysfunctional hormone production by adrenal glands

https://medlineplus.gov/genetics/condition/cushing-disease/
Dysfunctional hormone production by adrenal glands
Course Content

10.Fatty Acid Metabolism

10.1 Digestion and absorption of fatty acids.


10.2 Fatty acid synthesis.
10.3 Fatty acid oxidation.
10.4 Regulation of fatty acid metabolism.
10.5 Ketogenesis.
10.6 Changes in fatty acid metabolism in uncontrolled
diabetes and starvation.
10.7 The fate of cholesterol.

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