structure of cholesterol
Four fused rings (1 cyclopentane -, 3 cyclohexane- rings or derivatives thereof) • hydroxy group at C-3 (alcohol) Cholesterol • Double bond at C5=C6 in the B-ring
what's the structure of cholesterol ?
in the cytosol • mainly in the liver
where does mavelonate biosynthesis takes place?
Dimethylallyl pyrophosphate
1
1
1
relocation of the double bond of isopentenyl pyrophosphate
formation of geranyl pyrophosphate
whats head to tail condensation?
1. More hydrophobic than cholesterols
2. storage in the livers
3. transport of cholesterol
4. Obtained from the acylation of the fatty acids at the C3 of the hydroxyl group
What are cholesterols esters?
1. ApoA- 1 and ApoA- 2.
2. ApoA- 1V
3. Apo B- 48
4. Apo B- 100
5. Apo C- 1
6. Apo C- 11
7. Apo C-111
8. Apo D
9 Apo E
how many types of lipo proteins exist and what are the types of lipoproteins?
Modulates the fluidity of animal cell membranes – The cholesterol paradox: cholesterol can decrease or increase the membrane fluidity
2. Precursor of steroid hormones – Example: progesterone
3. Precursor of vitamin D
what are the functional roles of cholesterols in the body?
step one; condensation of the three acetate molecules into mevalonate
step two :conversion of mevalonate into activated isopropene
step three; Polymerization of six 5- carbon isoprene units (30 carbons) to form squalene
step four : Cyclization of squalene - forms 4 rings of the steroid nucleus
What are the summary steps in mavelonate biosynthesis?
head to head condensation
farnesyl pyrophosphate
to
squalene
Whats head to head condensation?
1. relatively hydrophilic cholesterol derivates
2. Synthesized in the liver
3. Aids in lipid digestion
what are bile acids?
ApoA- 1 and ApoA-11 are associated with high density lipo proteins
ApoA- 1 and ApoA-11 are associated with corresponding lipo proteins?
mavelonate dependent (animals, plants and cytosols)
mavelonate independent (plant chloroplast and many bacteria)
What are the two isoprenoid biosynthesis pathway ?
1. Thiolase reaction
acetyl-CoA------ H20~~~ CoA-SH (thiolase) -------acetoacetyl-CoA
2. HMG-CoA synthase reaction
3. HMG-CoA reductase reaction (Cytosol)
HMG-CoA----2 NADPH + 2 H~~~~CoA-SH + 2 NADP+ (HMG-CoA reductase )-----mevalonate
HMG-CoA reductase
1. integral membrane protein in the ER
2. different from mitochondrial HMG-CoA reductase, which plays a role in ketosis
3. carries out an irreversible reaction
4. is an important regulatory enzyme in cholesterol synthesis
whats the first step in mevalonate biosynthesis ?
Squalene monooxygenase rxn Introduction of an oxygen atom to form a squalene2,3- epoxide 2)
Cyclase reaction •
Synthesis of lanosterol (animals) •
Synthesis of stigmasterol (plants)
• Synthesis of ergosterol (many fungi)
what is involved in the conversions of squalene to sterols ?
Complexes of apolipoproteins and combinations of other lipids (phospholipids, cholesterol, cholesteryl ester, triacylglycerols)
what are plasma lipo proteins?
ApoA- 1V associated with HDL and chylomicrons
Apo1V is associated with which lipoproteins
A condensation reaction is the combination of two molecules to form a single molecule, usually with the loss of a small molecule such as water.
Whats a condensation reaction?
Three subsequent reactions that require ATP
(1) Mevalonate kinase (MVK) : GTP, UTP, & CTP can be used
(2) Phosphomevalonate kinase (PMK)
(3) Pyrophosphate mevalonate kinase
(4) Decarboxylation of 3-phospho-5-pyrophosphomevalonate to yield 3-isopentenylpyrophosphat
whats the second step in mavelonate biosynthesis ?
Six diseases have been identified
• 2 are caused by a deficiency in MVK •
A) Mevalonic aciduria – Profound developmental delay – Dysmorphic features, cataracts, anemia – Malabsorption and diarrhea
• B) HIDS (hyperimmunoglobulinemia D and periodic fever syndrome) – Patients mainly suffer from fever episodes
what are the defects of the malevonic pathway?
1. chylomicrons
2. VLDL very low density lipoprotein
3. LDL low density lipoprotein
4. HDL high density lipoprotein
what are the four groups of plasma lipoproteins in human?
Apo 48 is associated with chylomicrons
What are the associated with Apo 48 lipoproteins
Polymerization is a process through which a large number of monomer molecules react together to form a polymer
Whats a polymerization reaction ?
Isomerization of isopentenyl pyrophosphate (IPP) to dimethylallyl pyrophosphate (DMP) by IPP isomerase
isopentenyl pyrophosphate ---------------------(IPP isomerase) ----dimethylallyl pyrophosphate
Head-to-tail condensations: C5 C10 C15 C30
DMP + IPP geranyl pyrophosphate + PPi
geranyl pyrophosphate + IPP farnesyl pyrophosphate + PPi
2 farnesyl pyrophosphate squalene + 2 PP
Whats the third step in cholesterol synthesis ?
1. cholesterol esters
2. Bile acids
3. Biliary cholesterol
how many types of cholesterol derivates exist ?
• “apo” = lipid-free form of the protein
• specific lipid/ cholesterol carrier proteins that allow distribution of cholesterol and various lipids through blood system
• interact with specific receptors and/or modulate enzyme activity
what are apolipoproteins?
ApoB- 100 with VLDL and LDL
whats the associated lipoproteins with ApoB-100?