Lipids Flashcards
What are lipids
- one of the building blocks of the cell/body
- chemically diverse group of compounds that exhibit low solubility in water
- most lipids contain fatty acids or are derivatives of FAs (the exception is cholesterol which is a derivative of acetate)
- Fatty acids are carboxylic acids composed of a hydrocarbon chain with a carboxyl group at one end and a methyl group at the other end (omega methyl group)
Functions of lipids
structure of membranes, hydrophobic anchors for proteins in membranes, cell signaling, hormones, storage of energy
Membrane functions: enclose the cell, make borders of organelles, form transport vesicles (for secretory path), organize complex reactions for energy metabolism and cell to cell communication, barrier and selective permeability, flexibility
organelles have a unique lipid and protein composition, fluid mosaic -> allows lipids and proteins to move laterally in the plane of the membrane, membranes arent uniform and have rafts
Lipids are structural components of membranes Cardio lipin (its deficiency),
lipid composition differs between organelles:
Cardiolipid is high in mito (inner membrane), and is needed for enzymes involved in mitochondrial energy metabolism. Barth syndrome-> deficient cardiolipin synthesis that leads to infantile death, cardiomyopathy and decrease in ATP production
Lipids have an asymmetrical distribution between teh two monolayers of the bi layer: Phosphatidylserine is very high on the innermembrane as compared to the outer membrane
Classification and structural features of lipids
Membrane lipids:
Phospholipids:
Glycerophospholipids: have a glycerol head, with two fatty acids, and a phosphate and alcohol
Sphingolipids: sphingosine head, with one fatty acid, and a phosphate group with a choline group
Glycolipids:
Sphingolipids: sphingosine head, one fatty acid, and a mono or oligosaccharide
What are glycerophospholipids
Glycerol backbone with two fatty acid derivative tails (and a phosphate w/ alcohol)
Fatty acid components of C1 and C2 are hydrophobic. The saturated fatty acid C1 is saturated
Unsaturated fatty acids are attached to the C2 (like arachidonic acid)
The C3 of glycerol is hydrophillic (phosphate Alcohol)
the glycerophspholipids usually differ at the head (phosphotidyl- ethanolamine, choline, serine, glycerol, inosital aka PIP2) and cardiolipin and phosphatidic acid
Glycerophospholipids synthesis
Phosphatidic acid is the precursor in the synthesis of glycerphospholipids and triacylglycerols
Phosphatidic Acid:
- formed by adding two Fatty acids ( made from acyl-CoA) onto glycerol-3-phosphate (by acyl transferase)
- Glycycerol 3 phosphate is derived from reduction of dihydroxyacetone phosphate (a glycolitic intermediate)
Phosphatidic Acid is also made by:
- phosphorylation of diacylglycerol by DAG kinase
- hydrolysis of glycerophospholipid itself (by phospholipase D -salvage pathway)
Phosphatidates
Phosphatidates are derivatives of phosphatidic acid (all the glycerophospholipids)
Polar groups are esterified to what they need to be (phosphate moiety)
CTP- cytidine triphosphate is involved in the synthesis of phosphatidates (aka glycerophospholipids), its the second most important role
Functions of Glycerophospholipids/glycerophospholipid dervatives/ phosphatidates
IN Lungs
Pulmonary surfactant: synthesized and secreted by alveolar type 2 epithelial cells and forms a film covering the epithelial cells. It reduces surface tension in lung alveoli, and allows it not to collapse. Surfactant deficiency is the primary cause of neonatal respiratory distress syndrome. Surfactant is made of lipids and proteins with dipalmitoyl phosphatidylcholine DPCC being the most abundant phospholipid in the mixture
Phosphatidylserine (remember its in high conc. on the inner membrane)- is involved in cell signaling, it marks the cell as dying (apoptosis) by putting more PS on the outside membrane. It also occurs in activated platlets and is required to initiate blood clotting cascade
Phosphatidyl inositol PIP2-> needed in cell signaling
Phospholipase C cleaves PIP2 into DAG and IP3 (to release Ca from Endoplasmic reticulum, and activates protein kinase C)
Phospholipases
Phospholipases are enzymes that cleave phospholipids (on of the fatty acids that are released is the C2 arachidonic acid)
Removal of fatty acids from:
C1: (phospholipase A1): re esterifaction reactions with other fatty acyl CoAs
C2: (phospholipase A2): release of arachidonic acid to be used to synthesize eicosanoids
Cleavage at the C3 phosphodiester bond:
Phospholipase C: releases DAG (diacylglycerol)
Phosholipase D: Releases phosphatidic acid
Sphingolipids
Can either be a phospholipid or glycolipid:
Sphingolipids are found in all cell membranes but are in high concentration in the CNS cells
Like glycerophospholipids, sphingolipids have a polar head and two non polar tails
Sphinolipids dont contain glycerol but one molecule of long chain amino alcohol, sphingosine
Ceramide is the base compound of sphingolipids (the phosphatidic Acid of sphingolipids)
Different sphingolipids
sphingolipids differ by their polar head groups
The Sphingolipid that is a phospholipid:
Sphingo myelin (head groups are either phsophocholine or phosphoethanolamine)- abundant in myelin sheath
The sphingolipids that are glycolipids:
-neutral glycolipids (uncharged at ph7) have polar head groups with one (cerebrosides) or more (globosides) carbohydrates. They are found on the outer surface of PM
-negatively charged glycolipids (sialic acid) Gangliosides
have oligosaccharides with one ore more (N-acetylneuraminic acid, Neu5Ac). Neu5Ac is a sialic acid, found at high levels in brain, and outer surface of PM
Sphingolipidoses
Lysosomal storage disease
Defect in the degredation of sphingolipids in the lysosome causes disease
Lysosomal storage disease: family of progressive, degenerative, disease with multi organ involvement (skeletal deformaties, metral retardation, heart disease, decreased life expectancy), over 50 different kinds, genetic disorder, individually rare but as a group 1/6000 (most common genetic disorder in kids)
Caused by a dificiency of an enzyme necessary to breakdown macromolecules, resulting in accumulation of undegraded material in the lysosome
Degredation of phospholipids and sphingolipids: occurs in the lysosome by the action of hydrolytic enzymes (phospholipases and exoglycosidases)
Genetic mutation causes decrease or absent activity of the hydrolytic enzyme in the lysosome, substrate accumulates upstream of the catabolic reaction. Clinical complications are related to the organs where there is an accumulation of the substrate.
Specific sphingolipidoses
Taysachs: accumulate ganglioside GM2 because of a deficiency of hexosaminidase A. prevalent among Ashkanazu jews, death before 4, neurodegenerative disease
Fabry disease: accumulation in neutral glycolipid Gb3 due to a deficiency in alpha galactosidase A. X linked disease (men) decrease in life expectancy of 10-20 years due to renal/ card/ stroke complications. angikeratomas, corneal opacities, neuropathic pain, hypohidrosis
Eicosanoids
Fatty acid derivatives. Short lived, variety of effects on human tissues and cells (inflammation, fever and pain, reproduction, blood cots and blood pressure
Paracrine hormones: act as short range signaling molecules via GPCRs
3 classes: prostaglandins, thrombaxanes, leukotrienes
All eicosanoids are synthesized from arachidonic acid (polyunsaturated fatty acid) the precursor to arachidonic acid is linoleic acid (an essential fatty acid from food)
Arachidonic acid is a component of membrane phospholipids readily available for eicosanoid synthesis following phospholipase A2 cleavage in response to a hormone or stimulus)
Dietary linoleic acid-> membrane phospholipids to store arachidonic acid-> phospholipase A2 cleaves it off-> converted to prostaglandins/thromboxanes/leukotrienes-> exter paracrine hormonal effects
Mammals cant convert oleate to linoleate so you need to eat it.
Synthesis of Prostaglandins/Thromboxanes
Arachidonic acid is cyclized and oxidized by cyclooxagynase (COX) and prostaglandin H2 synthase
Mammals have 2 isoforms of COX that differs in their expression: COX1 is expressed in all cells, COX 2 has inducible expression in certain cells
The resulting 5 membrane ring (PGH2) makes prostaglandins different than other eicosanoids
Thromboxanes are synthesized from PGH2 by thromboxane synthase in platlets that converts the 5 ring into a 6 ring (oxane ring)
Asprin and ibuprofen inhibit the activity of COX
