Biosynthesis of Membrane Lipids and Steroids

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Biosynthesis of Membrane Lipids and Steroids
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Membrane Lipids and Steroids
Phospholipids

1. Phosphatidate is a common intermediate in
   synthesis of phospholipids and triacylglycerols
2. Cholesterol is synthesized from acetyl-CoA
3. Regulation of cholesterol synthesis at several
   levels
4. Derivates of cholesterols -gt bile salts, steroid
   hormones,

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Synthesis of Phospholipids and Triacylglycerols
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Phosphatidate is a Common Intermediate in
Synthesis of Phospholipids and Triacylglycerols
Phosphatidic acid (mammalians) is synthesized in
the endoplasmic reticulum and outer mitochondrial
membran Phosphatidic acid mainly synthesized
from dihydroxyacetone phosphate (glycolysis)
R1 is usually saturated
R2 is usually unsaturated
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Synthesis of Triacylglycerols
Synthesized in Endoplasmic reticulum of the
liver Transport of TAG from liver to muscles (for
energy conversion) or adipocytes (storage)
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Phospholipids
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Phospholipids
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Activation of Intermediate for Synthesis of
Phospholipids
(Cytidine diphosphate)
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Synthesis of Phospholipids
Phosphatidic acid
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Synthesis of Phospholipids
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Ether Lipids are Found in Archae Bacteria
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Special Ether Phospholipid
PAF involved in allergic and inflammatory
responses
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Plasmalogen Special case of Phosphatidycholine In
many tissues plasmalogens -gt minor constituents,
In heart tissue nearly 50 of phosphatidylcholine
contains the alkenyl ether at position sn-1.
Nervous tissues, testes and kidneys also contain
significant amounts of plasmalogens. Ether-contai
ning phospholipids can protect cells against the
damaging effects of singlet oxygen, which at high
concentrations can kill cells.
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Sphingolipids
XH -gt Ceramide
Sphingolipids are found in plasma membrane of
Eukaryotes -gt Produced from Ceramides Highest
concentration in central nervous system Possible
role of lipids second messangers -gt i.e.
initiate cell death
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Synthesis of Sphingolipids
Gangliosides
Cholera doxin -gt binds to gangliosides
-gt Development of cholera (severe
diarrhea) Gangliosides are crucial for binding
of immune System cells to sites of injury
(inflammation)
Sphingolipids
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Usage of Lipids
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Steroids
Cholesterol
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Synthesis of Cholesterol
Cytosol
Endoplasmatic Reticulum
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Synthesis of Cholesterol 1st stage takes place
in the cyctosol
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Regulation of Cholesterol Biosynthesis

• Cholesterol obtained from
• 1. Diet
• 2. Synthesized de novo
• Synthesis in mammals Liver and Intestine
• Regulation of synthesis mainly by feedback
  regulation of 3-hydroxy-3-methylglutary CoA
  reductase (HMG CoA reductase)
• Rate of synthesis of mRNA of reductase
  (controlled by transcription factor SREBP)
• Rate of translation of reductase
• Degradation of reductase
• Phosphorylation decreases activity
• Regulatory mechanism are modulated by receptors
  that sense cholesterol on blood

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Transport of Cholesterol and Triacylglycerols
-gt Cholesterol Triacylglycerols are transported
as lipoprotein particles -gt Synthesized and
secreted by liver and intestine Role of protein
component (Apoproteins) solubilize hydrophobic
lipids contain cell targeting signal
Lipoprotein particles are classified according
to their density
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Core of hydrophobic lipids surrounded by a shell
of more hydrophilic lipids
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In the liver -gt some cholesterol converted into
bile salt
Diet
Triacylglycerols Cholesterol
High in Triacylglycerol content (99) -gt low
density
Cholesterol of diet
LDL is major carrier of cholesterol in blood and
regulates de novo synthesis -gt High
LDL -gt Bad Cholesterol -gt Atherosclerosis HDL
(Good cholesterol) is a shuttle that moves
cholesterol throughout the body -gt to use it or
to produce hormones
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Regulation of Cholesterol Biosynthesis
Diet
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LDL Regulates Cholesterol Metabolism

• Endocytosis of LDL bound to its receptor
• Apoprotein B-100 (on surface of LDL) binds to
  specific receptor
• Receptor-LDL complex initiates endocytosis
• Vesicles fuse with Lysosomes -gt Break down of
  Protein and Lipids (Lipase)
• Cholesterol can be used for membrane biosynthesis
  or reesterfied for storage

Cholesterol synthesis Liver cell engaged in
synthesis and secretion of VLDL
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Receptor-Mediated Endocytosis
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Cholesterol Biosynthesis Blocker
Potent blocker of HMG CoA reductase -gt reduce
level of synthesized cholesterol
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Cholesterol Derivates Bile Salts
The only way we can get rid of excess of
cholesterol -gt cholesterol derivates -gt mainly
produced bile salts !!!
cysteine
Major bile salt
Bile salts are cholesterol derivates. -gt highly
efficient detergents, help to solubilize dietary
lipids -gt synthesized in liver, stored in gall
bladder, released into small intestine
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Cholesterol Derivates Steroid Hormones
(Androgens)
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Nomenclature of Steroid Hormones
Steroid hormones are hydroxylated by Cyt P450
3a or 3ß hydroxy
5a or 5ß hydrogen
Below plane
Above plane
Trans fusion Steroid hormones
Cis fusion Bile salts
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Synthesis of Precursor for Steroid Hormones
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Synthesis of Progesterone and Corticosteroids
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Synthesis of Androgens and Estrogens
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Synthesis of Vitamin D
In the liver kidney
Plays an important role in Calcium and Phosphorus
metabolism
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Isoprenoids
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ß-Carotinoids
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