Biochem - Unit 2 - Biosynthesis Of Sterols

Front 1

Location of synthesis and metabolism of cholesterol

Back 1

synthesis - all somatic cells
metabolism - majority in liver

Front 2

Is plasma membrane cholesterol esterified or unesterified?

Back 2

free, unesterified

Front 3

Structure/characteristics of cholesterol

Back 3

4 rings, 27 carbons, amphipathic due to polar head (-OH), low solubility

Front 4

First stage of cholesterol synthesis

Back 4

1) Thiolase converts two Acetyl-CoA to acetoacetyl-CoA
2) HMG-CoA synthase adds an Acetyl-CoA forming Beta-Hydroxy-Beta-methylglutaryl-CoA (HMG-CoA)
3) HMG-CoA Reductase oxidizes 2NADPH, reducing HMG-CoA to mevalonate

Front 5

Rate limiting step of cholesterol synthesis

Back 5

conversion of HMG-CoA to mevalonate by HMG-CoA Reductase (an integral membrane protein)

Front 6

Second stage of cholesterol synthesis

Back 6

6-carbon mevalonate is converted via a decarboxylation step to the 5-carbon activated isprene

Front 7

Third stage of cholesterol synthesis

Back 7

5C isoprene -> 10C geranyl pyrophosphate -> 15C farnesyl pyrophosphate -> C30 squalene

condensation of farnesyls for form squalene involves oxidation of NADPH

Front 8

Fourth stage of cholesterol synthesis

Back 8

squalene -> squalene 2,3-epoxide -> lanosterol (has all four rings)-> cholesterol

squalene monooxygenase converts squalene into squalene 2,3- epoxide requiring NADPH and O2 (produced H2O and NADP)

Front 9

Inherited Disorders of Cholesterol Synthesis

Back 9

All exhibit developmental malformations due to lack of cholesterol modification of developmental morphogens (Hedgehog family)