MCB 2000 Lecture Notes - Lecture 31: Hmg-Coa Reductase, Acetyl-Coa, Lanosterol

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Lecture 31
Cholesterol
Cholesterol
Found in gallbladder
Steroid hormones
Vitamin D
Component of membranes
High cholesterol is defect in regulation of synthesis or uptake via LDL particle
Two ways it can be regulated metabolically
Cholesterol is not usually from diet, body usually makes it
Requirements for Cholesterol Biosynthesis
Begins in cytosol with mevalonate from acetyl CoA
Enzyme that catalyzes it is thiolase
HMG-CoA created
HMG-CoA Reductive is the rate limiting step
Formation of Activated Isoprene Units
Mevalonate → 3 ATP molecules consumed → activated isoprene unit
Isoprene: 5C unit, help make up CoQ as its tail
Cholesterol lowering drugs: statin
Usually also take CoQ to combat muscle weakness
Isomerization
Isopentenyl pyrophophate → diphenyl alanenyl
Pay attention to color coding
4 steps
5C to 30C really fast
Move to ER
Cyclaizaiton and Hydroxylation Rxns
In presence of NADH and O2
Squalene → epoxide → protosterol → lanosterol → cholesterol
Be familiar with this rxn
HMG-CoA Reductase
Rate limiting step, principale site of regulation in cholesterol synthesis
Is regulated in multiple ways
Not regulated allosterically
Regulated by phos-dephos
Regulated by amount (gene expression and protein degradation)
- Cholesterol regulates its own biosynthesis through changes in gene expression and degradation
of HGM CoA
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Document Summary

High cholesterol is defect in regulation of synthesis or uptake via ldl particle. Two ways it can be regulated metabolically. Cholesterol is not usually from diet, body usually makes it. Begins in cytosol with mevalonate from acetyl coa. Hmg-coa reductive is the rate limiting step. Mevalonate 3 atp molecules consumed activated isoprene unit. Isoprene: 5c unit, help make up coq as its tail. Usually also take coq to combat muscle weakness. Squalene epoxide protosterol lanosterol cholesterol. Rate limiting step, principale site of regulation in cholesterol synthesis. Regulated by amount (gene expression and protein degradation) Cholesterol regulates its own biosynthesis through changes in gene expression and degradation of hgm coa. Response element here is the sterol response element: responds to level of steroids in the cell through a transcription factor. Srebp: ( ) transcription factor following cholesterol"s cleavage in the golgi. Response elements: dna sequences that bind specific transcription factors to increase gene.

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