Complex lipids week 3 Flashcards
The hydrophobic and hydrophilic domains are bridged by a glycerol moiety in glycerophospholipids and by a _____ in sphingomyelin and glycosphingolipids.
Where are glycerophospholipids, sphingolipids, and cholesterol are found primarily in what cellular locations?
- sphingosine
- cellular and intracellular membranes
What is the fxn of sterols and eicosanoids?
Sterols (steroid hormones) and eisocanoids (prostaglandins, thromboxanes) are bioactive molecules, regulating cellular processes.
Eicosanoids act like hormones. Have a short half life.
T or F: Typically one of the FA chains in phospholipids and sphingolipids are unsaturated.
True. Increases membrane fluidity.
What is the simplest glyerophospholipid? What is it composed of?
What are the 3 general components of phospholipids?
Phosphatidic acid is the simplest glycerophospholipid, composed of a diacylglycerol and a phosphate group esterified to the third carbon of glycerol.
Glycerophospholipids contain 1,2-diacylglycerol and a base connected to the phosphate group by a phosphodiester bridge.
What are the bases present in phospholipids?
What are the most abundant phospholipids? What other names do they go by?
- serine, ethanolamine, choline, inositol, glycerol
- The most abundant glycerophospholipids are phosphatidylcholine (also called lecithin), phosphatidylethanolamine (also called cephalin) and phosphatidylserine.
At physiologic pH, what are the charges of lecithin, cephalin, phosphatidlyserine, and phosphatidylinositol?
At physiologic pH, phosphatidylcholine and phosphatidyl ethanolamine have no net charge and exist as dipolar “zwitterions”, while phosphatidylserine has one net negative charge. Phosphatidylinositol is an acidic glycerophospholipid (-1 charge) found in mammalian cell membranes.
What phospholipid plays a role in bile? What role does it play in bile?
What can impairment of this phospholipid production and secretion result in?
The detergent properties of phospholipids, especially phosphatidylcholine, play an important role in bile where they function to solubilize cholesterol. Impairment in phospholipid production and secretion into bile can result in the formation of cholesterol stones and bile pigment gallstones.
What phospholipid plays a role in lung sufractant? What develops in babies and adults without sufficient surfactant?
Phophatidyl choline is an important component of lung surfactant – the extracellular fluid layer of the alveoli. It plays role in allowing the alveoli to re inflate in a lower pressure, thus preventing alveolar collapse. Respiratory distress syndrome in preterm babies is due to insufficient production of the surfactant (needs to be 32 weeks of gestation). This can be monitored from the amniotic fluid. This can also occur in adults who take immunosuppressive or chemotherapeutic drugs.
What lipid serves as a source of arachadonic acid? What is synthesized from arachodonic acid?
Phosphatidylinositol (rarely phosphatidylcholine) serves as sources of arachidonic acid for synthesis of prostaglandins, thromboxanes, leukotrienes and related compounds.
What phospholipid serves as a signal transducer when hydrolyzed? What is it hydrolyzed into?
Phosphatidylinositol serves as a signal transducer, releasing two active second messengers: diacylglycerol and inositol phosphate. (IP3 releases Ca2+ from IP3 gated Ca2+ channels)
Where is cardiolipin present?
Where are plasmalogens found? (cellularly and in the body)
What is the fxn of platelet activating factor?
A. Cardiolipin
Function: Present in the inner membrane of mitochondria and in bacterial membranes. This lipid is antigenic. In clinical laboratories, it is recognized by antibodies raised against Treponema pallidum, the bacterium that causes syphilis.
Plasmalogens
Function: Important lipids in membranes, e.g. phophatidalethanolamin in nerve tissue, phosphatidalcholine in heart muscle.
Platelet activating factor
Function: A bioactive molecule that plays role in triggering thrombotic and acute inflammatory events. For example: it causes platelet aggregation and degranulation; and activates inflammatory cells.
What intermediate is used both for TG and phospholipid synthesis?
What are the 2 general ways in which phospholipids can be synthesized?
- The initial pathway for the biosynthesis of triacylglycerols and glycerophospholipids are similar, both use phophatidic acid as an intermediate.
- The branch point in the biosynthesis of glycerophospholipids occurs following cleavage of glycerol 3- phosphate and the generation of 1,2 diacylglycerol.
- Glycerophosholipids can be synthesized in two ways. Either phosphatidic acid reacting with a base or an activated base-phosphate reacting with diacyl glycerol.
Explain the synthesis of lecithin.
Where are choline and ethanolamine obtained for lecithin and cephalin production?
- Lecithin (and other phospholipid synthesis) shares a common pathway with TG synthesis. FACoA is esterified with G3P to form lysophosphatidic acid. Another FA is added to form phosphatidic acid. To form lecithin, choline is phosphorylated. choline phosphate is then esterified with glycerol to form lecithin.
- Choline and ethanolamine are obtained from diet or reutilized after the turnover of phospholipids. Reutilization and uptake of choline is important since humans cannot synthesize it in sufficient amounts (essential dietary nutrient).
How is phosphatidylserine (PS) synthesized? What process does the liver use PS for?
This molecule is synthesized by exchanging bases, ethanolamine to serine. PS is used in liver to produce PC when choline is not available since liver uses PC in the bile and to assemble lipoproteins.
What are phospholipases?
Where is phospholipase A1 found? What is its fxn?
- Phospholipases hydrolyze the phophodiester bonds of glycerophospholipids. Each enzyme cleaves at a specific site .These enzymes are responsible for the digestion of dietary phophoglycerides as well as cleaving membrane-bound ones for the release of signaling molecules or arachidonic acid. “Remodeling” of phosphoglycerides in membranes is also possible by these enzymes.
- Phospholipase A1: present in most cells to cleave off fatty acid from position 1
What are the two locations of phospholipase C (PLC)? What is the difference in its fxn in its respective locations?
Phospholipase C: membrane bound form is part of signal transduction, liberates IP3 and DAG from phosphatidylinositol.
In liver lyosomes, PLC degrades phospholipids (not involved in signal transduction). The bases can be reused for synthesis of other phospholipids.
Where are sphinglipids found in the body? Where are they found in the highest concentration?
What is the backbone of sphingolipids? How is it different from glycerol?
Sphingolipids are present in blood and nearly all body tissues, with the highest concentrations in the nerve tissues. Various sphingolipids are components of the plasma membrane of nearly all cells.
Sphingosine is the backbone of the sphingolipids. It is similar to glycerol; however, C2 always bears a fatty acid linked by an amide bond rather than an ester bond (C2 OH is replaced by an NH2 group that binds the fatty acid). Although C3 OH is always free, C3 is extended with an unsaturated C15 alkyl chain.
In what 3 ways can sphingolipidases be diagnosed?
Specifically, how can Gaucher’s disease be diagnosed?
How can these diseases be treated?
Diagnosis: by measuring enzyme activities in cultured fibroblasts or peripheral leukocytes, or by DNA analysis.
Histological examination of the affected tissue can be diagnostic, for example, wrinkled tissue paper appearance of the lysosomes in macrophages (that are filled by undigested glucocerebrosides) is typical of Gaucher’s disease.
Treatment: is possible with recombinant enzyme replacement therapy, but expensive. When macrophages are affected (such as in Gaucher’s disease), bone marrow replacement is helpful.
What are the 2 pathwyas of acracidonic metabolism? What types of enzymes are involved and what is produced from each pathway?
In mammalian cells, two major pathways of arachidonic acid metabolism produce important mediators of cellular and bodily functions: the cyclooxygenase and the lipoxygenase pathways. The cyclooxygenase pathway leads to a series of compounds including prostaglandins and thromboxanes, while the lipoxygenase pathway leads to leukotrienes.
What are the 2 types of drugs that interfere with prostaglandin production?
Give names of drugs in these classes and state what enzymes they interfere with.
Two types of drugs affect prostaglandin metabolism:
- Steroidal anti-inflammatory drugs like hydrocortisone, prednisone, and betamethasone block prostaglandin release by inhibiting phospholipase A2 activity to interfere with mobilization of arachidonic acid.
- The nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicyclic acid), indomethacin and phenylbutazone, block prostaglandin production by inhibiting cyclooxygenase.
