Membranes

Question 1

Glycerophospholipids

Answer 1

Consists of a polar head groups and fatty acids that are attached to a glycerol backbone Example include. They are the most abundant lipid component of membranes. They are glycerol-based compounds with two hydrophobic fatty acid chains that can differ in length (normally between 14 to 24 carbon atoms). One hydrophobic tail usually has one or more cis-bonds (double bond, i.e. it is unsaturated) while the other tail does not (i.e. it is saturated). Each double bond creates a small kink in the structure of the tail. The two tails are linked to glycerol via ester linkages. The hydrophilic head of a glycerolphospholipid molecule in the case of Phosphatidylcholine consists of a phosphate group attached to the glycerol backbone again via an ester linkage as well as choline further attached to the phosphate group also through an ester linkage.

Question 2

Sphingolipids

Answer 2

They consist of polar head groups and fatty acids attached to a sphingosine backbone Examples include; Sphingomyelin, Glycosphingolipids (a.k.a glycolipids)

Question 3

Cholesterol

Answer 3

amphipathic. Consists of a small polar head, steroid ring structure and short fatty acid tail

Question 4

How are glycerophospholipids named?

Answer 4

The different glycerolphospholipid molecules are named after the side groups attached to the phosphate group. For example, phosphatidylcholine has a choline group; phosphatidylethanolamine has an ethanolamine group; phosphatidylserine has a serine group etc.

Question 5

Ceramide

Answer 5

Sphingosine + fatty acid

Question 6

sphingomyelin

Answer 6

Sphingosine + fatty acid = ceramide

ceramide + phosphate + choline = sphingomyelin

Question 7

ceramide + sugars = ?

Answer 7

glycolipids –> galactocerebrosides or gangliosides

Question 8

Cerebrosides

Answer 8

(e.g. galactocerebrosides) are important in nerve tissues and prevalent in the membranes of brain cells.

Question 9

Gangliosides

Answer 9

(acidic glycosphingolipids) are the most complex sphingolipids, and are found primarily in the ganglion cells of the central nervous system. Gangliosides are of medical interest because several lipid storage disorders involve the accumulation of NANA (N-Acetyl Neuraminic Acid)-containing cells.

Question 10

glycolipids

Answer 10

sphingolipids that contain carbohydrates attached to them. They are found in greatest amounts in nerve tissues and are located in the outer leaflet of the plasma membrane, where they interact with the extracellular environment. glycolipds found ONLY in the outer leaflet, with carbohydrate portions exposed on the cell surface.

Question 11

outer leaflet lipid distribution

Answer 11

The ‘outer leaflet’ (which faces the outside of the cell) consists mainly of phosphatidylcholine and sphingomyelin + glycolipids exclusively on this side. +even distribution of cholesterol on both leaflets

Question 12

lipid distribution in the membrane

Answer 12

outer leaflet: mainly phosphatidylcholine and sphingomyelin + glycolipids are exclusively found here. inner leaflet: consists mostly of
phosphatidylethanolamine,
phosphatidylserine and
phosphatidylinositol.
Cholesterol is evenly distributed among the bilayer.
Depending on the type of cell/organelle, the plasma membrane composition can vary significantly.

Question 13

inner leaflet lipid distribution

Answer 13

consists mostly of
phosphatidylethanolamine,
phosphatidylserine and
phosphatidylinositol.
\+even distribution of cholesterol on both leaflets

Question 14

Lipid Rafts

Answer 14

more rigid and dense than other portions of the membraneSphingomyelin and glycolipids tend to cluster in small semi-solid patches termed lipid rafts, which are enriched with cholesterol and GPI-anchored proteins. Certain membrane proteins with long enough membrane-spanning segments preferentially partition into the lipid rafts. Several proteins that are typically found in the membrane bilayer (such as G proteins and several protein kinases) can move in and out of rafts during the cell signaling process. The transient presence of these proteins in rafts allows for the clustering that is necessary for processes such as endocytosis and receptor-mediated signaling. Some rafts are stabilized by interactions with the cytoskeleton through peripheral membrane proteins.

Question 15

Membrane fluidity

Answer 15

Lipids with saturated fatty acids pack more densely in the membrane and provide less fluidity.
Membrane fluidity is also affected by the length of fatty acid chains. Short fatty acid chains increased membrane fluidity when compared to long chains.Higher temperatures - in general - favor increased fluidity. As a lipid bilayer cools, it eventually undergoes a phase change in which it becomes a gel-like solid (and loses fluidity). However, the effects of temperature are dependent on fatty acid chain length and saturation status. Short fatty acid chains and high unsaturation lowers the phase transition temperature.

Question 16

Cholesterol’s effects on membrane fluidity

Answer 16

depends on temperature. At high temperatures, the bulky steroid rings of cholesterol interfere with the movement of the fatty acid chains and reduce fluidity. At lower temperatures an opposite effect has been observed. By interfering with interactions between fatty acid chains, cholesterol prevents membranes from freezing and maintains membrane fluidity.

Question 17

Lipid-anchored membrane proteins of the cytosol

Answer 17

In the cytosol, proteins can be anchored to the bilayer by a covalently-attached, hydrophobic fatty acid tail. A number of growth signaling proteins whose function depends on their association with the plasma membrane (such as the signaling protein Ras) are modified in this way.

Question 18

Lipid-anchored membrane proteins

Answer 18

these are covalently linked to a membrane-embedded lipid via a fatty acid chain or an oligosaccharide chain

Question 19

Integral Membrane Proteins

Answer 19

anchor themselves within the bilayer via stretches of hydrophobic amino acids located in specific regions of the protein

Question 20

peripheral proteins

Answer 20

Peripheral proteins are loosely associated (via electrostatic force or H-bonds) with Integral Membrane Proteins through protein-protein interactions and can be dissociated from membranes by relatively mild processes (e.g. high salt solution washing, metal chelating agents, or pH changes).

Question 21

Myristic Acid

Answer 21

Fatty acid which is covalently attached to specific amino acids within in protein to make a lipid anchored protein. Protein attachment site = N-terminus (glycine). Fatty acid length = 14-Carbon

Question 22

palmitic acid

Answer 22

Fatty acid which is covalently attached to specific amino acids within in protein to make a lipid anchored protein. Protein attachment site = internal cysteine residue. Fatty acid length = 16-Carbon

Question 23

Prenyl group

Answer 23

Fatty acid which is covalently attached to specific amino acids within in protein to make a lipid anchored protein. Protein attachment site = c-terminus (cysteine). Fatty acid length = 15-Carbon (farnesyl group) 20-Carbon geranyl geranyl group

Question 24

Lipid anchored membrane proteins outside of the cell

Answer 24

Proteins on the outer surface of the cell can be tethered to the plasma membrane via a glycophosphatidylinositol (GPI) anchor. Enzymes residing in the membrane of the cell can cleave the phoshatidylinositol moiety to release the GPI-linked protein from its association with the membrane.

Question 25

glycophosphotidylinositol (GPI) anchor

Answer 25

only present on the outside of cells. proteins can be tethered to the plasma membrane via GPI anchor, and enzymes residing in the membrane of the cell can cleave the GPI moeity to release the GPI-linked protein from its association with the membrane.

Question 26

Mobility of plasma membrane proteins

Answer 26

influenced by: interactions with cytoskeletal elements like actin, interactions with the ECM like collagen, Tight junctions between neighboring epithelial cells restrict lateral diffusion of proteins (ie the brush border cells of the intestine, proteins that regulate transport of nutrients into and out of the cell are restricted to certain regions of the cell surface. and also lipid rafts influence mobility.

Question 27

Lipid associated diseases:

Answer 27

multiple sclerosis, Niemann-Pick Disease

Question 28

Membrane protein associated diseases:

Answer 28

cystic fibrosis, Duchenne muscular dystrophy

Question 29

Glycosylation-related diseases

Answer 29

e.g. congenital disorders of glycosylation

Question 30

The Glycocalyx In The Intestine

Answer 30

The microvilli of the intestine are covered by a thick glycocalyx coat. This layer is made up of glycolipids and glycoproteins that are bound to the lumenal surface of enterocytes (absorptive epithelial cells). The glycocalyx provides an additional surface for absorption and also contains glycosylated enzymes that participate in the digestion of macromolecules. In the intestine, the glycocalyx also protects the underlying epithelium from friction and exposure to digestive enzymes and microorganisms.

Question 31

Multiple Sclerosis (MS)

Answer 31

The myelin sheath, which insulates nerve cell axons, is rich in both sphingomyelin and galactocerebrosides. In multiple sclerosis (MS), an autoimmune response leads to the destruction of the cells which produce myelin. As myelin disappears (demyelinization), nerve cells lose the ability to transmit electrical signals. MS can affect vision, sensation, coordination, movement, and bladder/bowel control. Typically, symptoms initially appear as episodic attacks but may gradually worsen over time.

Question 32

Niemann-Pick Disease

Answer 32

Sphingomyelin can accumulate in a rare hereditary disease called Niemann-Pick Disease (types A and B). It is a genetically-inherited disease caused by a deficiency in the enzyme sphingomyelinase, which results in the accumulation of sphingomyelin in the spleen, liver, lungs, bone marrow, and brain, causing irreversible neurological damage. Of the two types involving sphingomyelinase, type A occurs in infants. It is characterized by jaundice, an enlarged liver, and profound brain damage. Children with this type rarely live beyond 18 months. Type B involves an enlarged liver and spleen, which usually occurs in the pre-teen years. The brain is not affected. Most type B patients present with <1% normal levels of the enzyme in comparison to normal levels. Nieman-Pick type C is associated with a different mutation, and manifests as a buildup of cholesterol and glycolipids in liver, spleen and neural cells.

Question 33

sphingolipidoses.

Answer 33

sphingolipidoses. In addition to Niemann-Pick disease, the other main members of this group are, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease and Metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but Fabry disease is notably X-linked. Altogether, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available for treating Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The infantile forms of sphingolipidoses are generally fatal by age 1 to 5 years, but progression may be mild for juvenile- or adult-onset forms.

Question 34

Cystic Fibrosis

Answer 34

Cystic Fibrosis is a disease in which a defective Cl– transporter in epithelial cells results in abnormally thick, sticky mucus which obstructs respiratory passages. The cystic fibrosis gene encodes a protein (CFTR or cystic fibrosis transmembrane conductance regulator) in the ABC transporter family.

Question 35

Congenital Disorders of Glycosylation (CDG)

Answer 35

Defects in the glycosylation pathway lead to aberrant glycolcalyces on the cell membrane proteins. CDG type I occurs as a result of missing oligosaccharide chains while CDG type II is characterized by abnormal oligosaccharide chains. CDGs manifest as developmental disorders, autoimmune diseases, sporadic cancers, and metabolic stress