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