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140 Cards in this Set
- Front
- Back
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4 main classes of lipids:
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1. Fatty acids
2. Steroids 3. Lipid vitamins 4. Terpenes |
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5 classes of Fatty Acid Lipids:
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1. Eicosonaoids
2. GlyceroPhospholipids 3. Triacylglycerols 4. Waxes 5. Sphingolipids |
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2 categories of Glycerophospholipids:
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1. Ether phospholipids
2. Phosphatidates |
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2 Ether phospholipids:
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1. PAF (plt actvtng factor)
2. Plasmalogens |
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Phospholipids:
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1. Phosphatidyl ethanolamines
2. Phosphatidylserines 3. Phosphatidylcholines 4. Phosphatidylinositols |
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Sphingolipids are precursor to:
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Ceramide
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Derivatives of Ceramide:
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1. Sphingomyelins
2. Cerebrosides 3. Gangliosides |
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Lipid is a general term for:
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Substances that are Water-insoluble and extractable by polar solvents.
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2 main types of constituents make up complex lipids:
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1. Fatty acids
2. Isoprene units (5C) |
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Eicosanoids are derived from:
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arachidonic acid
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triacylglycerols derive from
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fatty acids
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ceramides are derived from
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sphingosine
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how are phospholipids similar to triglycerides?
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Both constructed on glycerol backbone
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The basic unit of Phospholipids is:
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phosphatidic acid
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how are phospholipids different from triglycerides?
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Phosphatidic acid has phosphate esterified to C3 instead of a fatty acid.
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Where do phosphlipids function?
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As the major class of membrane lipids
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What part of phospholipids mediates their biolog function?
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Hydrophilic (phosphate) - affects surface properties of membrane.
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What is the important intermediate in phospholipid and triglyceride synthesis?
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Phosphatidic acid
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Where is phosphatidic acid synthesized? What is unique about synthesis?
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-Endopl. reticulum + outer Mito Membrane
-De Novo |
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How is Phosphatidic Acid formed?
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By adding 2 FA onto Glycerol-3-Phosphate
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What transfers the FA to glycerol-3-P?
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Specific acyltransferases
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What is the specificity of Aceyltransferase I and II in making phosphatidic acid?
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Acyltransf 1: SATURATED fatty acid attached to C1
Acyltransf 2: UNSATURATED FA attached to C2 |
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Where is Glycerol-3-phosphate coming from in this process?
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Dihydroxyacetone Phosphate (DHAP) from glycolysis - reduced
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What reduces DHAP to Glycerol-3-P?
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NADH
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Phosphatidates are
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Lipid derivatives of phosphatidic acid
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4 groups that get added to Phosphatidic acid:
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-Ethanolamine
-Serine -Choline (these 3 most common) -Inositol |
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How are phosphatidates made?
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By esterifying the phosphate with one of the polar groups.
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What is Phosphatidylcholine?
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Lecithin
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What is the common feature of Phosphatidyl-ethanolamine/serine and Lecithin (choline)?
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-Most abundent lipids in mammalian cell membranes
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What are the FA groups at C1 and C2 in phosphatidylinositol?
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C1: stearic acid
C2: arachidonic acid |
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What is important about phosphatidylinositol?
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Primary intracellular source of arachidonic acid
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How many carbons in:
-Stearic acid -Arachidonic acid |
Stearic = 18
Arachidonic = 20 |
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How many doub bonds in
-Stearic aa -Arachidonic aa |
Stearic = none
Arachidonic = 4 -> (5/8/11/15) |
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What is the essential molecule needed to form phosphatidate lipids?
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CTP
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REMEMBER THIS UNTIL THE DAY YOU DIE: "Regardless of the pathway used,
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The 2nd most important biochemical role of CTP (after Nucleic Acid biosynth) is PHOSPHOLIPID BIOSYNTHESIS"
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How is the synthesis of Phosphatidylserine unique?
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Takes place by exchange of Serine for PhosphatidylETHANOLAMINE
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What are Ether Phospholipids?
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Phospholipids with an Ether at the C1 carbon.
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Ether phospholipids are synthesized from:
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-Dihydroxyacetone
-Long chain FA -Long chain Fatty alcohols |
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What adds the ether linkage to a phospholipid?
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An enzyme in peroxisomes
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2 Types of Ether Phospholipids:
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-PAF (pltlet activating factor)
-Plasmalogens |
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What is PAF's function?
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Mediates
-allergy -inflammatory responses -anaphylactic shock |
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Where is PAF synthesized and released from?
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PMNs - neutrophils
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What is the biochemical point of interest about PAF?
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-Acetyl replaces FA at C2
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What is the effect of replacing the C2 FA with Acetyl?
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Increased solubility and ability to function in aqueous environmt
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Polar group in PAF is usually:
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Choline
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How are Plasmalogens different from PAF, structurally?
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The ether at C1 is a,B-unsaturated.
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Location/type of enzyme that makes Plasmalogens?
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In the ER - mixed function oxidase
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What are Ether-linked lipids associated with (in high amts)?
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Invasive ability of metastatic cancer cells - exhibit these lipids in plasma membranes.
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What tissues have large amts of:
-Ethanolamine plasmalogen -Choline plasmalogen |
Ethanolamine = myelin
Choline = cardiac |
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So main difference between PAF and Plasmalogens:
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Ether group on Plasmalogens has a double bond in it (just adjacent to the ether bond.
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What are Phospholipases?
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Family of enzymes that specifically cleave phospholipids
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What do Phospholipases do?
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Remodel phospholipids for intracellular signalling
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4 Types of Phospholipase that I should know:
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Phospholipase A1
Phospholipase A2 Phospholipase C Phospholipase D |
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Phospholipase A1
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Removes FA at C1
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Phospholipase A2
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Removes FA at C2
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Purpose of A1/A2's action:
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allow the FA to change to something else
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Phospholipase C
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Cleave C3 phosphodiester to make Diacylglycerol (leaves an O on C3 but takes PO3 off)
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Phospholipase D
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Cleave C3 phosphodiester to make
Phosphatidic acid (leaves PO3 on C3 and takes an O off) |
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Products of cleaving PIP2 (phosphatidylinositol 4,5-bisphosphate) by phospholipase C:
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-DAG (diacylglycerol)
-IP3 (Inositol 1,4,5-triphosphate) |
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What are DAG and PI3
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important intracellular signals
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So PIP2 cleavage produces
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DAG + IP3
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Where is PIP2 located and what is its function?
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On inner surface of cell membrane; binds signal molecules sent from extracellular signals binding their receptors (ie hormones)
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What causes Phospholipase C to cleave PIP2?
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Gprotein - the product of signal cascade initiated by hormone binding.
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What results from PLC cleavage of PIP2?
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-DAG stays in the membrane
-IP3 is soluble - travels to ER to open IP3-gated Ca2+ channels |
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What can DAG do from its membrane-associated position?
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Activate Protein Kinase C - with the help of Ca2+ released by IP3
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What is the main function served by phospholipids?
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To anchor membrane associated proteins.
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Name of phospholipids that anchor extracellular proteins (LPL and Acetocholine Esterase):
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GPI - Glycosyl Phosphatidyl Inositol
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Key characteristics of GPI:
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-GlcN/Man short oligosacc bonded to C-term of protein
-Phosphoethanolamine residue in btwn above 2 |
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How are GPI-linked extracellular proteins released?
(glycosylphosphatidylinositol) |
By Phospholipase C Cleavage
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How are GPI-linked extracellular proteins generally arranged?
(glycosylphosphatidylinositol) |
In clusters
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How do intracellular proteins become attached to the cytosolic side of membranes?
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Through specific interaction of long-chain FA's and ISOPRENOIDS
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What does Palmitic acid bind?
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An internal Cysteine residue
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What does Myristic acid bind?
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An N-terminal glycine residue
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What are Farnesyl and Geranylgeranyl?
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Polyisoprene units
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What do Farnesyl and Geranylgeranyl bind?
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C-terminal Cystein residue
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What is the main distinction between Eicosanoids and Phospholipids?
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Eicosanoids lack a glycerol backbone
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What is the precursor to Eicosanoids?
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Arachidonic acid
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Structure of Arachidonic acid:
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20:4(5,8,11,14)
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What is the precursor to arachidonic acid?
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Linoleic acid
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Structure of Linoleic acid:
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18:2(9,12)
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What are Eicosanoids?
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Paracrine hormones - not transported via blood, just act right on cells nearby point of synthesis.
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Why are Eicosanoids shortlived?
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-Rapid mitochondrial turnover
-Metabolized by B-oxidation in Peroxisomes |
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3 classes of Eicosanoids:
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1. Prostaglandins
2. Thromboxanes 3. Leukotrienes |
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2 Pathways for Eicosanoid synthesis:
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1. Cyclooxygenase
2. Lipoygenase |
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How is Arachidonic acid available for Eicosanoid synthesis?
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It is part of the structure of Phosphatidylinositol - at C2; This phosphatidate is in membranes
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What releases Arachidonic acid from Phosphatidylinositol?
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Phospholipase A2
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What enzymes make Leukotrienes?
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Lipoxygenases
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What is the central enzyme in the Cyclooxygenase Pathway?
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PGS - Prostaglandin Synthase
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What enzyme makes Prostaglandin from Arachidonate?
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PGH2 - Prostaglandin H2
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So what pathway is used to make:
-Prostaglandins and Thromboxane? -Leukotrienes? |
-Prostaglandins/Thromboxane are made via the Cyclooxygenase path
-Leukotrienes via Lipoxygenase |
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What 2 enzymes are in Prostaglandin Synthase?
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1. Cyclooxygenase
2. Glutathione-dependent peroxidase |
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What is Prostaglandin Synthase composed of? (2 parts)
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1. COX = cyclooxygenase
2. Glutathione-dependent peroxidase (PG Hydroperoxidase) |
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What is essential for COX to work?
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2 molecules of oxygen
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What does COX do?
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Cyclizes C8-C12 on Arachidonic A to form Prostaglandin G2 (PGG2)
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What is the distinct difference between Prostaglandins and other eicosonoids?
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The 5-membered ring in what used to be Arachidonate
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What step occurs in prostaglandin synthesis after PGG2 is formed? Enzyme?
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PG hydroperoxidase forms Prostaglandin H2 (PGH2)
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What are the 2 isoforms of PGS (Prostaglandin Synthase)? Where are they located?
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#1. Constitutive - in most tissues and cells.
#2. Inducible - limited sites |
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How do the prostaglandin derivatives differ?
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By functional groups attached to the 5-membered ring.
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So what is the intermediate precursor to all prostaglandins?
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PGH2
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What are the 2 key structural differences between prostaglandins and leukotrienes?
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1. PG's have reduced double bonds; Leukotr. retain same #.
2. PG's have a 5-C ring; Leukotrienes don't. |
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What do Prostaglands do in general?
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Stimulate uterine smooth muscle contraction, increase body temp, induce inflammation/pain.
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What does PGI2 (prostacyclin) do specifically?
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Prevents clotting
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What opposes Prostacyclin?
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PGE2 - Promotes clotting
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How are Thromboxanes made?
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By converting cyclopentane into a 6 membered oxane ring.
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What is the function of Thromboxane?
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Blood clotting/reduced blood flow to clot site.
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What is different about oxygen requirements for leukotriene vs. prostaglandin synthesis?
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Prostaglandin - 2 molecules O2
Leukotrienes - 1 molecule O2 |
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What cells have PGS2 (synthase)?
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Macrophages and monocytes
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When is PGS2 expressed?
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Only when certain agents stimulate it - PAF (Plt activator - Ether phospholipid)
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So the effect of PGS2 is:
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elevated levels of prostaglandins, so inflammation.
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What is the mechanism of Corticosteroids?
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Inhibit phospholipase A2 which reduces arachidonic acid production.
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What is the effect of Corticosteroids?
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Antiinflammitory
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How do NSAIDS work?
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By inhibiting the COX activity of PGS; arachidonate is available, but not put to use.
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What is the most effective NSAID and why?
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Aspirin - covalently acetylates COX and blocks its active site.
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ONTO LEUKOTRIENES
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ok
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By what pathway are leukotrienes synthesized?
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Lipoxygenase pathway
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What is the precursor of leukotrienes?
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Arachidonic acid - its the precursor of all eicosanoids.
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Lipoxygenase catalyzes the ____ of arachidonate, where Cyclooxygenase (COX) catalyzes the ____ of it.
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Monooxygenation instead of dioxygenation
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What member of the lipoxygenase family is most important in humans?
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5-LO
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Which double bond in Arachidonate is 5-LO spcf for?
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C5-C6
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What molecule is formed by monooxygenating the C5 double bond of arachidonate?
(think friend) |
5-HPETE
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under what conditions is 5-HPETE produced?
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When human tissues/cells undergo inflammatory processes.
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What is formed by the loss of water from 5-HPETE?
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Leukotriene A4 (LTA4) - an epoxide
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What is the 4 in LTA4 referring to?
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The # of double bonds - 4
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How is LTA4 converted to LTB4?
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By adding water to the C11-12 double bond - breaks apart the epoxide and leaves 2 -OH groups
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How is LTA4 converted to LTC4?
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GSH (reduced) adds to C6, cleaving the epoxide
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How is LTD4 formed?
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By loss of glutamate from LTC4
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How is LTE4 formed?
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By loss of glycine from LTD4
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What is the unusual characteristic of GSH that is important to remember?
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Unusual linkage between Glu-Cys-Gly
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What are LIPOXINS?
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Products of multiple lipoxygenase pathways; have OH groups attached to C5 and C6
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What are the characteristic activities of lipoxins?
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Inhibit leukotrienes - anti-inflammatory
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What is the other alternative fate of 5-HPETE (versus leukotriene synth)?
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5-HETE - more stable than 5-HPETE
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How does 5-HETE form?
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The C5-OOH redues to C5-OH - either spontaneously or by a peroxidase catalyst.
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Prostaglandins exert their effect by paracrine signalling, where Leukotrienes do it by
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Receptor-ligand interaction
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What type of disorders are associated with elevated leukotrienes?
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Inflammation and Hypersensitivity reactions (asthma/anaphylactic shock)
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What protein is 5-LO dependent on?
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FLAP - 5 lipoxygenase activating protein
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What is FLAP?
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An integral nuclear membrane protein - binds Arachidonate, allows it to interact w/ 5-LO
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What is the function of LTB4?
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Chemotaxis - attracts PMNs to combat infection.
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What 'term' describes the group functionality of LTC4/LTD4/LTE4?
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Slow-reacting substances of anaphylaxis (SRS-A)
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What are the effects of SRS-A, and in whom are they seen?
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-Bronchoconstriction
-Gastroconstriction In ppl w/ hypersensitivity |
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Mechanism of asthma drugs Singulair and Accolate:
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Blocks binding of leukotrienes to lung smooth muscle cell receptor.
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