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