Cholesterol Flashcards
What does steroid structure look like
The steroid structure consists of four planar carbon ring that is very hydrophobic due to the C and H it contains, to which side groups can be added to form different steroids
Where is cholesterol for physiological requirements in body synthesised
Cholesterol for physiological requirements in synthesised in the liver
In what three parts can the biosynthesis of cholesterol be split
The biosynthesis of cholesterol can be split into 1. the synthesis of isopentenyl pyrophosphate, 2. the condensation of isopentenyl pyrophosphate to form squalene, 3. the cyclisation and demethylation of squalene to form cholesterol
Where do these steps of cholesterol synthesis take place
The synthesis of isopentenyl pyrophosphate takes place in the cytoplasm, the formation of squalene and then cholesterol take place in the endoplasmic reticulum
What are the end products from step 1 and 2 of cholesterol synthesis
The end product of step 1 is acetoacetyl-coA and HS-coA and of step 2 the end product is 3-hydroxy-3-methylglutaryl-coA (HMG-coA) and HS-coA
After double condensation of Acetyl-CoA, what is product
The product of double condensation of acetyl-coA is 3-hydroxy-3-methylglutaryl-coA (HMG-coA)
Which reducing agent is used to reduce this substance and what is the product in step 3 of cholesterol synthesis
NADPH is used to reduce HMG-coA and the product is mevalonate, and byproducts NADP+ and HS-coA
What is the enzyme that catalyses this reaction and how is it controlled
HMG-coA reductase catalyses this reaction and is controlled via product inhibition by its product mevalonate, its ultimate end product cholesterol and bile salts
What happens to mevalonate to form 3-isopentyl pyrophosphate
Mevalonate undergoes sequential phosphorylation (three times) and then a decarboxylation and dephosphorylation to form 3-isopentyl pyrophosphate
What do isoprene units attached to molecules confer to these biomolecules
Isoprene units can be attached to molecules to make them have hydrophobic lipophilicity and be able to sit in lipid bilayers
Where and what for is dolichol phosphate used
Dolichol phosphate is a lipid in the endoplasmic reticulum that is involved in the N-linked glycolysation of proteins
How is ubiquinone (coenzyme Q) confined to inner membrane of mitochondrion
Ten isoprene units are added to pre-coenzyme Q to confer it the lipophilicity it needs to sit in the mitochondrial inner membrane
What are the products of condensation reactions of two and three 3-isopentyl pyrophosphate groups called
The products of condensation of two 3-isopentyl pyrophosphate is geranyl pyrophosphate and when a third 3-isopentyl pyrophosphate is added this produces farnesyl pyrophosphate
How many carbons is squalene and how is it synthesised
Squalene consists of 30 carbon atoms and is formed after the condensing of two farnesyl phosphate molecules with NADPH as reducing agent
In the last part of cholesterol synthesis, how is lanosterol changed to cholesterol
Lanosterol is converted to cholesterol in 19 steps that result in three times demethylation and reduced to form cholesterol
Which type of enzymes are involved in the last step of cholesterol synthesis
Moxooxygenases and cyclases are involved in the last step of cholesterol synthesis to induce the cyclation of squalene to lanosterol which is then further converted to cholesterol
In what primary bile salt can cholesterol be converted and what other bile salt
Cholesterol can be converted in the liver to form primary bile salt glycocholate or can also be converted to taurocholate
What precursor is made from cholesterol to form steroid hormones
Cholesterol can be converted by desmolase to pregnenolone which is the precursor for all five classes of steroid hormones
What are the five classes of steroid hormones
The five classes of steroid hormones are progestagens, glucocorticoids, mineralocorticoids, androgens and oestrogens
What types of substances are vitamin D and what are they used for
Vitamin D are a group of steroid compounds that bind to intestinal wall to allow for the uptake of ions like calcium, phosphate and magnesium that are needed for bone development.
How is calcitriol synthesised and what is its function
Calcitriol is synthesised from cholecalciferol (vitamin D3) by twice hydroxylation and this active form of vitamin D can bind to vitamin D binding elements in nucleus and induce transcription of key genes for bone development
What is rickets and what is its cause
A development disease due to deficiency of vitamin D3 during childhood that leads to abnormal bone formation with soft and weak bones
What is prenylation
Prenylation is a post-translational modification in which a farnesyl or geranyl-geranyl group is added to a cysteine residue
How is the emulsification function of bile salts enabled
When cholesterol is converted in the liver, a hydrophilic group is added to its tail, a carboxyl group in glycocholate and a sulfate group in taurocholate
What type of genetic disorder is familial hypercholesterolaemia
Familial hypercholesterolaemia is a dominant monogenetic disorder
What symptoms can be seen in heterozygous individuals with FH
In individuals with heterozygous FH two to three times higher blood cholesterol levels are found
What symptoms can be seen in homozygous individuals with FH
In individuals with homozygous FH more than five times higher blood cholesterol levels are found and often coronary infarction and severe atherosclerosis occur already in adolescence
What is a xanthoma
Xanthomas are cholesterol-rich superficial fatty deposits due to high LDL levels that lead to scavenging and deposits by macrophages that become foam cells
What receptor is dysfunctional in FH and how many mutations can cause this disorder
In familial hypercholesterolaemia the LDL receptor that is found on hepatocytes and other somatic cells is dysfunctional. This can be caused by more than thousand different mutations.
What things can happen to the receptor because of these mutations
The mutations that lead to FH can affect LDLR synthesis and expression, LDL binding, LDLR recycling and endocytosis which can all lead to FH
What is the effect of resins on cholesterol levels
Resins prevent the reuptake of cholesterol-bile acid complexes, lowering LDL by 15-30% and increasing HDL by 3-5%
Which enzyme do statins inhibit and how and what is its function
Statins bind to HMG-coA reductase and it inhibits the formation of mevalonate by competitive inhibiting the enzyme that is involved in the cholesterol synthesis pathway, by which they decrease the cholesterol produced by the body
