Lipids

Question 1

Fatty Acids

Answer 1

Fatty acrids are carboxylic acids composed of a hydrocarbon chain

Most lipids contain fatty acids or are derived from fatty acids

Question 2

Storage Lipids

Answer 2

Fatty acids are esterified to glycerol, forming triacylglycerols

• Triacylglcerol contains a single glycerol molecule linked to three fatty acids.
• Adipocytes store large amounts of triacylglycerols as fat droplets that nearly fill the cell.
• Lipases are enzymes that release the fatty acids, which are subsequently oxidized to yield energy.

Question 3

Biological Membranes - Cardiolipin and Barth syndrome

Answer 3

Cardiolipin is a phospholipid particulary abundant in mitochondria where it is required for optimal function of numreous enzymes involved in mitochondrial energy metabolism

In Barth Syndrome, infantile death occurs due to deficient cardiolipin synthesis. Decreased mitochondrial ATP productions –> cardiomyopathy and general weakness

Question 4

Asymmetric distribution between the two monolayers of the bilary

Answer 4

Phosphatidylserine is found on the inner monolayer of the plasma membrane - facing the cytoplasm

Question 5

Phospholipids - Glycerophospholipids

Answer 5

Phospholipids are constructed on glycerol bckbone except that PO4 is esterified at C3 instead of fatty acid

• Phosphatidic acid is the parent compound from which other phospholipids can be synthesized by modificaiton of PO4 group
• Linked to highly polar or charged “head group” by a phosphodiester linkage
• Majority have a net negative charge at ph7
  
  • PE and PC are neutral at pH7

Question 6

Phosphatidic Acid (PA) Synthesis

Answer 6

PA is formed by adding two fatty acids onto glycerol-3-phosphate by acyl transferases

• Glycerol 3 Phosphate is primarily derived from reduction of the glycolytic intermediate, dihydroxyacetone phosphate

Question 7

Fatty Acid Incorporation

Answer 7

1) Triacylglycerols for the storage of metabolic energy
2) Phospholipd components of membrane

Partitioning is dictated by the body’s needs. In times of rapid growth, synthesis of new membranes requires production of membrane phospholipds, and in times of abundant food supply and non active growth periods, mostly fatty acids are shunted into triacylglycerols for storage of metabolic energy.

Question 8

Alternative PA Synthesis

Answer 8

1) Phosphorylation of diacylglycerol (DAG) by DAG kinase
2) Phospholipase D-mediated hydrolysis of phosphatidylcholine

Question 9

Phosphate Group in Phosphatides

Answer 9

The phosphate group is supplied by cytidine diphosphate (CDP). The second most important role for CTP (after nucleic acid synthesis) is phospholipid biosynthesis.

Question 10

Pulmonary Surfactant

Answer 10

Surface forces in alveolar structs are countered by pulmonary surfactant that reduce surfice tension

• Surfactant is synthesized and secreted by alveolar type II epithelial cells
  
  • forms a film covering the cells
• Deficiency is the primary cause of neonatal respiratory distress syndrome (RDS) and surfactant supplementation in premature infants with RDS significiantly reduces mortality in these patients

Pulmonary surfactant is a complex mixture of lipids and proteins with dipalmitoylphosphatidylcholine (DPCC) being the most abundant and phosphatidylglycerol being the second most abundant phospholipid.

Lipids constitute ~90% of the composition

Question 11

Phosphatidylserine (PS)

Answer 11

Change in the distribution of PS to the outside of the plasma membrane marks a cell as dying and undergoing a process called apoptosis

• In a healthy, living cell, PS is vastly in the inner monolayer

Question 12

Phospholipases

Answer 12

Specifically cleave phospholipids and are involved in phospholipid remodeling and intracellular signaling

• Phospholipase A1 remove fatty acids from C1
• Phospholipase A2 removes fatty acids from C2
• Permits re-esterificaiton with other fattyl acyl CoAs or release of arachidonic acid (from C2)
• Phospholipase C and D cleave teh C3 phosphodiester to produce either DAG or Phosphatidic acid, respectively.

Question 13

Phosphatidylinositols (PIs) and Cell Signaling

Answer 13

Phospholipase C cleaves Phosphatidylinositol 4,5 bisphosphate (PIP2) to produce two products that are active in signaling

• Diacylglycerol (DAG)
• Inositol 1,4,5-triphosphate (IP3)
  
  • soluble and triggers release of Ca++ from the ER.
  • Combines with DAG which stays in cell membrane to activate protein kinase C (PKC).

Question 14

Membrane-associated Proteins

Answer 14

Glycosyl Phosphatidylinositol (GPI) anchor allows proteins to attach to extracellular membrane

• Peripheral proteins with covalentyl attached lipid

Question 15

Ether Phospholipids - Platelet-activating factor (PAF)

Answer 15

PAF induces platlet aggregation and the release of serotonin (vasocontrictor) from platelets, and stimulates smooth muscle contraction.

Also mediates hypersensitivity and anaphylactic shock.

• Causes these effects by binding to an extracellular receptor on target cells

Question 16

Sphingolipids

Answer 16

Particularly abundant in cells of the CNS

Like phospholipds, they contain a polar head group and two nonpolar tails, however sphingolipids do not contain glycerol, but one molecule of the long-chain amino alcohol, sphingosine.

When a fatty acid is attached to the amide group at C2 of sphingosine, the resulting comound is a ceramide, which is structurally similar to diacylglycerol.

*Ceramide is the base compound of the sphingolipids (like phosphatidic acid is of phospholipids)

Question 17

Sphingomyelins

Answer 17

contain phosphocholine as their polar group

No net charge on their polar head group at ph 7

especially abundant in myelin, the membranous sheath that surrounds and insulates the axons of some neurons

Question 18

Gangliosides

Answer 18

The most complex sphingolipids with polar groups comprised of oligosaccharides with one or more N-acetylneuraminic acid.

• Neu5Ac is a sialic acid and gives gangliosides a negative charge at pH7
• found at highest concentration in the nervou system, particularly the gray matter of the brain

Question 19

Lysosomes

Answer 19

Phospholipids and Sphingolipids are degraded in lysosomes by the action of hydrolytic enzymes, including phospholipases.

Degradation of sphingolipids produces sphingosine and fatty acids

Question 20

Lysosomal Storage Diseases

Answer 20

Occur when hydrolytic enzymes are compromised causes the substrate to accumulate in the lysosomes of tissues responsible for its catabolism

Tay-Sachs and Niemann-Pick both caused by abnormal accumulation of spingolipids

• exhibit severe neurological defects

Question 21

Eicosanoids

Answer 21

Fatty acid derivatives that are short-lived

Family of paracrine hormones that act as short-range singaling molecules , affecting tissues near the cells that produce them.

• Mediate their effect by interacting with cell surface G-protein coupled receptors

Question 22

Eicosanoids - 3 Classes

Answer 22

1. Prostaglandins (5 membered ring)
2. Thromboxanes (6 membered ring)
3. Leukotrienes (no ring)

All eicosanoids are synthesized from arachidonic acid

• Precursor is linoleic acid (required in diet as essential fatty acids)
• component of membrane phospholipids which make it ready available for eicosanoid synthesis following phospholipid A2 cleavage

Question 23

Cyclooxygenase Pathway

Answer 23

Cyclooxygenase (COX) cyclyzes and oxidizies arachidonic acid

• composed of cyclooxygenase and glutathione-dependent peroxidase activites
• COX-1 is constitutively expressed in many tissues
• COX-2 exhibits inducible expression in selected cell types

Thromboxanes are synthesized from PGH2 by thromboxane syntahse in platelets that converts teh cyclopentane ring into a 6 membered oxygen containing (oxane) ring.

Question 24

Leukotrienes

Answer 24

Linear molecules with 4 double bonds (3 in serines forming a triene)

• Arachidonic acid is converted to leuoktrienes by lipoxygenases (forming a -OOH_ group on the molecule
• Major leukotrienes produced by 5-lopoxygenase