Membrane Lipid Biosynthesis

1
Membrane Lipid Biosynthesis

• Medical Biochemistry
• Lecture 51

2
METABOLISM OF ACYLGLYCEROLS AND SPHINGOLIPIDS

• Triacylglycerols are the major energy-storing
  lipids, whereas phosphoglycerols, sphingomyelin,
  and glycosphingolipids are amphipathic and
  fulfillmany roles, ranging from structural
  functions in cell membranes to specialized
  functions, i.e., precursors for hormone second
  messengers, lung surfactant, and
  platelet-activating factor.

3
  Biosynthesis of Triacylglycerols and
Phosphoglycerols   - They are formed by acylation
of triose phosphates.
4
(No Transcript)
5
(No Transcript)
6
Biosynthesis of Glycerol ether
phospholipids   -This pathway is exclusively
located in peroxisomes.
7
(No Transcript)
8
  Phospholipases allow degradation and remodeling
of phosphoglycerols
9
All Sphingolipids are formed from
Ceramide   Ceramide is synthesized in the
endoplasmic reticulum.
10
Glycosphingolipids are a combination of Ceramide
with one or more sugar residues

• The simplest glycosphingolipids (cerebrosides)
  are galactosylceramide (GalCer) and
  glucosylceramide (GlcCer). 
• GalCer is the major lipid of myelin, whereas
  GlcCer is the major glycosphingolipids of
  exteraneuronal tissues and a precursor for most
  of the more complex glycosphingolipids.

11
UDPGlc Uridine diphosphoglucose UDPGal
Uridine diphosphogalactose
12
CLINICAL ASPECTS

• Deficiency of lung surfactant causes Respiratory
  Distress Syndrome. Lung surfactant is a
  secretion with marked surface-active properties
  and prevents the alveoli from collapsing.  
• It is mainly composed of lipids, i.e.,
  dipalmitoylphosphatidylcholine which is
  synthesized shortly before parturition in
  full-term infants. Preterm new-borns have this
  syndrome due to deficiency of lung surfactant. 
• Administration of either natural or artificial
  surfactant has been useful. 

13
Phospholipids Sphingolipids are involved in
Multiple Sclerosis (M.S.) and Lipidoses

• MS is a demyelinating disease, there is loss of
  both phospholipids and of sphingolipids from
  white matter. Thus, the lipid composition of
  white matter resembles that of gray matter. The
  cerebrospinal fluid shows raised phospholipid
  levels. 
• Sphingolipidoses are a group of inherited
  diseases that are often manifested in childhood.
  These diseases are part of a larger group of
  lysosomal disorders. 
• There is an accumulation of complex lipids that
  have a portion of their structure in
  common-Ceramide.  
• The enzymatic defect in each of these diseases is
  a deficiency due to gene mutation of a specific
  lysosomal hydrolytic enzyme necessary to break
  down the lipid or of a key activator protein of
  the enzyme.

14
(No Transcript)