sphingolipids and cholesterol

sphingolipids

Membrane components of all eukaryotic cells

Concentration is highest in cells of the central nervous system

Derivative of the amino alcohol sphingosine

C1, C2 and C3 of the sphingosine backbone are structurally analogous to the three glycerol carbons

ceramides

N-acyl derivatives (amide bond with fatty acid) of sphingosine

phosphosphingolipids - sphingomyelins

Ceramide with phosphocholine or phosphoethanolamine

Most common sphingolipid in most cell membranes

Myelin sheath around nerve axons are rich in sphingomyelin

simple glycosphingolipids - cerebrosides 

Ceramides with a polar head group that consists of a single sugar. Most common sugar residues: galactose and glucose

complex glycosphingolipids - globosides/gangliosides

Ceramides with attached oligosaccharide

Located at the cell surface, sugar head group extends beyond the surface of the cell membrane

globoside

a ceramide whose head group is a neutral oligosaccharide

gangliosides

a ceramide with attached oligosaccharide containing at least one sialic acid (acidic sugar) residue, wither N-acetylneuraminate (NAMA) or N-glycolylneuraminate.

Especially abundant in brain membranes - 6% of brain lipid

Tay-Sachs disease (fault in lipid degradation)

Gangliosides are normally degraded in lysosomes by sequential removal of their terminal sugars

Faulty enzyme N-aceytlhexoseaminidase leads to an inability to degrade gangliosides

Neurons become significantly swollen with lipid filled lysosomes

Fatal neurological deterioration in early childhood

function of glycolipids

In membrane lipids, the oligosaccharide head extends beyond the cell surface, often acting as a receptor.

cell recognition

Blood types: specific glycolipids on red blood cells determine ABO blood groups

receptors for bacteria toxins and viruses

Cholera toxin binds to GMA1 ganglioside on intestinal epithelial cells -> enter the cell

Cell-cell interactions and immune function

P-selectin (lectin) in the plasma membrane of endothelial cells bind to carbohydrate motifs on glycolipids of leukocytes and mediates rolling adhesion at an infection site

steroids

Lipids mainly in eukaryotic organisms

Consist of 4 fused rings

Often methyl groups at C10 and 13, longer alkyl chain (8-10 carbons) at C17, oxygen (hydroxyl or carbonyl group) at C3

Steroids with C3 hydroxyl groups are sterols

cholesterol 

Membrane component

Modulates the fluidity of animal cell membranes

Precursor of many signalling molecules including steroid hormones

Obtained from diet or synthesised by the body in the liver or intestine

lipoproteins

transport triacylglycerols and cholesterol throughout the organism

lipoproteins consist of

• Core pf hydrophobic lipids

• Shell of more polar lipids and proteins

low density lipoprotein (LDL)

Major carrier of cholesterol in blood

Single molecule apoprotein, B-100, larger protein (514kd)

Key role in controlling cholesterol metabolism

Defects in LDL metabolism increases serum cholesterol

mutation/dysfunction of LDL receptor

atherosclerosis risk

plant sterols

Plants contain little cholesterol, but synthesise other sterols

Plant sterol structures are slightly different from other cholesterol

Not absorbed by intestine cells but block absorption of cholesterol

Use in diet to reduce cholesterol intake

cholesterol derivatives

synthesised from cholesterol

modifications

• Hydroxylation

• Introduction of double bond

• Shortening of alkyl chain at C17

steroid hormones

• Water insoluble

• Bind proteins for transport to their target tissues

• Steroid-hormone-receptor complexes act as transcription factors to regulate gene expression

vitamin D

Steroid (cholesterol) derivative

Steroid B ring disrupted between C9 and C10 by UV light

Enzymatic hydroxylation in the liver at C25 and the kidneys at C1 produces the active form

The dietary supplement of vitamin D2 (ergocalciferol) is structurally similar to D3

active vitamin D increases

intestinal absorption of Ca2+

vitamin D deficiency

can lead to rickets

vitamin D intoxication

can lead to kidney stones

vitamin D also modulates

immune response

variation in skin pigmentation 

thought to have evolved to control vitamin D levels