Biochemistry Sixth Edition

Chapter 26

The Biosynthesis of Membrane Lipids and Steroids

Copyright 2007 by W. H. Freeman and Company

Berg Tymoczko Stryer

Applications

Lipid synthesis - Microbial production of biodiesel

Steroids synthesis

Cholesterol how to control your diet

Antifungal drugs

Biochemistry Phosphoglycerides, Cholesterol, Steroids Lecture

http://www.youtube.com/watch?v=MgTAw1TMmPg

http://www.youtube.com/watch?v=XJvBOKOeipM

Summary lipid synthesis

Synthesis of Phosphatidate

Synthesis of Phospholipids and Triacylglycerol

Phosphatiditic acid phosphatase key regulatory

enzyme

Synthesis of sphingolipids from ceremide

DHAP

Glycerol 3-P

dehydrogenase

NADH NAD+

Glycolysis

Gluconeogenesis

Glycerol phosphate

acyltransferase

Phosphatidic acid

phosphatase

Diglyceride acyltransferase

CTP PPi

Alcohol is

Inositol

Different alcohols gives

different phospholipids

Phospholipids and

Triacylglycerols

Ceramide and

Sphingolipids

TCA Citrate

Acetyl CoA

Malonyl CoA

Cholesterol

FAD

FADH2

Sphingosine, sphingosine 1-P, and ceramide serve

as second messengers in the regulation of cell growth,

differentiation and death.

Summary Cholesterol synthesis

Synthesis of Cholesterol from Acetyl-CoA

Regulation of Cholesterol Biosynthesis at several

levels

Cholesterol and TAG transport by lipoproteins

Important derivatives of Cholesterol

Cholesterol is synthesized from Acetyl CoA

All 27 C-atoms are derived from Acetyl CoA.

This steroid modulates the fluidity of animal membranes.

3-Isopentenyl pyrophsphate is an activated isprene molecule that is an

important biomolecule throughout the kingdoms of life.

Cholesterol Biosynthesis

Ergosterol in the fungal pathogen Aspergillus fumigatus

Regulation of Cholesterol Biosynthesis

The SREBP pathway.

SREBP resides in the endoplasmic reticulum, where it is bound to SCAP by its regulatory (Reg) domain. When cholesterol levels fall, SCAP and SREBP move to the Golgi complex, where SREBP undergoes successive proteolytic cleavages by a serine protease and a metalloprotease. The released DNA-binding domain moves to the nucleus to alter gene expression

Lipoprotein particles and cholesterol metabolism

Bile salts, the major breakdown

Products of cholesterol.

Cholesterol is the precursor of the 5 major classes

of steroid hormones: prostagens, glucocorticoids,

mineralocorticoids, androgens and estrogens.

These hormones are powerful signal molecules

that regulates a host of organismal functions.

Participate in gene regulation.

Vitamin D is derived from cholesterol by the ring-splitting activity of light

Pregnancy

Pregnancy

Gluconeogenesis

Kidney Na+, K+, H+

Cytochrom 450 mechanism:

Hydroxylation of cholesterol