Cholesterol Flashcards
What are the 6 types of metabolic reaction
Redox, ligation requiring ATP cleavage, isomerisation, group transfer, hydrolysis, addition or removal of functional groups
How is cholesterol synthesised
In the liver, de novo from Acetyl CoA Great need as membrane component 500mg/day dietary uptake
What 3 steps are involved in cholesterol biosynthesis
Synthesis of isopentenyl pyrophosphate, an activated isoprene (key building block, cytoplasmic) Condensation of 6 molecules of IPP to form squalene (cytoplasmic) Cyclisation and demethylation of squalene by monooxygenases to give cholesterol (ER reaction);
How are steroid hormones synthesised
Cholesterol->pregnenolone via desmolase enz All 5 steroid hormones come from pregnenolone; Progestagens, glucocorticoids, mineralocorticoids, androgens, estrogens
What can cholesterol be broken down to to aid digestion
Bile salts glycocholate and taurocholate
What is vitamin D
Collective term for steroid s which are vital for intestinal absorption of important ions for bone development eg calcium, phosphate and magnesium.
What activity does UV light cause on 7-dehydrocholesterol Describe the role of one of these products What does deficiency in one of these products cause
Production of vitamin D metabolites eg calcitrol which is the most active and plays a key role in calcium metabolism, steroid hormone which induces key genes involved in bone metabolism Vitamin D3 deficiency in childhood leads to rickets (bone development defect)
What is the monogenic dominant trait in which cholesterol transportation is defective called
Familial hypercholesterolaemia
What are the effects of familial hypercholesterolaemia (FH)
Heterozygotes- serum cholesterol is 2-3x higher, more susceptible to atherosclerosis (artery hardening) Homozygotes- serum chol 5x higher, severe atherosclerosis and coronary infarction in adolescence.
How is cholesterol taken up by cells and why is this not the case in FH
Chol in form of LDL taken up by LDL receptor on cell surface. Patients with FH lack functional LDLRs; over 1000 LDLR mutations lead to FH. Can affect receptor expression, LDL binding or endocytosis and recycling.
What is used to inhibit de novo cholesterol synthesis by the liver
HMG-CoA reductase inhibitors, aka Statins Eg Lipitor, Crestor Lovastin competitively inhibits HMG-CoA reductase, as it resembles 3-HMG substrate
What are resins/sequestrants
Drugs that reduce dietary cholesterol absorption by the intestines Eg cholestyramkne (questran, prevalite) Bind to/ sequester bile acid-cholesterol complexes reverting resbsorptioj by intestine. Lower LDL and raise HDL
Which step of cholesterol synthesis is under control of negative feedback
HMG-CoA reduction to Mevalonite. Enzyme HMG-CoA Reductase is allosotericslly inhibited by mevalonate, cholesterol and bile salts
