Metabolism of steroids and other lipids

CJW

Learning Objectives & Outcomes

This lecture will emphasize on the following topics; which the students are expected to understand at the end of this lecture.

1. Biosynthesis of cholesterol.

2. Biosynthesis of steroids, phosphoglycerides& sphingolipid. Respiratory distress syndrome.

3. Eicosanoids(biosynthesis, roles and applications).

Cholesterol biosynthesis

Biosynthesis of cholesterol

To synthesize steroids, first we must study the formation of cholesterol

Cholesterol is synthesized in almost all tissues in human; predominantly in liver, intestines, adrenal cortex, reproductive tissues

It is a 27 Carbon molecule

Components: Acetyl-CoA + NADPH + ATP

Way points in cholesterol synthesis

Acetyl-CoA (2C)HMG-CoA (6C)

Mevalonic acid (6C)

Isopentenyl-pyrophosphate (5C) IPPDimethyl allyl pyrophosphate (5C) DAPP

Geranyl pyrophosphate (10C) GPPFarnesyl pyrophosphate (15C) FPP

Squalene (30C)

Lanosterol (30C)

Cholesterol (27C)

Mevalolic acid / mevalonate

Very similar to fatty acid synthesis, the building block for cholesterol is acetyl-CoA

3 Acetyl-CoA (2C) HMG-CoA (6C)

E1: Thiolase (to take away CoA)E2: HMG-CoA Synthase

Process is driven by the hydrolysis of CoA high energy thioester bond

Mevalolic acid / mevalonate

Another similarity to FA synthesis; NADPH is used as a main reductant

E: HMG-CoA reductase(rate-limiting)

Remove the last CoA

Expression of this enzyme is inhibited by Cholesterol

Like any feed-back inhibition

Cholesterol synthesis

From mevalonate onwards, to cholesterolMulti-step process

Points:-(1) ATP is used to prime the substrates pyrophosphatePyrophosphate compounds are high energy compoundsIts hydrolysis drives pyrophosphatase enzymes

(2) Isopentenyl pyrophosphate (IPP) adds (5C)

(3) NADPH is used to squalene synthesis and cyclization lanosterol