Complex lipids week 3 Flashcards
(38 cards)
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 does phospholipase A2 do? Where does it act? (2 places)
What are differences in its role in the 2 locations that it acts in?
What is it activated by?
Phospholipase A2: present in many cells and in pancreatic juice to cleave off fatty acid from position 2
The pancreatic enzyme is activated by trypsin and digests dietary phospholipids.
Intracellularly, releases arachidonic acid (the precursor of prostaglandins) from phosphatidyl inositol.
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.
When sphingosine is substituted with a FA in C2, it is a _____.
ceramide
Depending on how ceramide is further substituted, there are 5 categories of sphingolipids. What are they?
- sphingomyelin
glycosphingolipids
- cerebrosides
- globosides
- gangliosides
- sulfatides
What is ceramide subtituted with to form sphingomyelin? Where is sphingomyelin mostly found?
Sphingomyelin: ceramide is substituted with phosphorylcholine (only sphingolipids that are phospholipids). Found mostly in brain, the sphingomyelin of myelin contains mostly longer chain fatty acids, while that of gray matter, mostly stearic acid.
Describe the synthesis of sphingosine and ceramide.
Synthesis of sphingosine occurs by the condensation of serine and palmitoic acid followed by decarboxylation and desaturation of the chain. Addition of a fatty acid to the NH2 group on C2 gives ceramide. Transfer of additional groups at the C1-OH occurs with the help of different specific transferases.
How are sphingolipids taken up by cells for degradation? Where in the cell are they degraded? What enzymes are used?
What kinds of cells in blood degrade sphingolipids?
What is the majority type of sphingolipid in the brain? During which developmental period is the turnover of sphingolipids most extensive?
Sphingolipids are taken up by cells by endocytosis. They are normally degraded within lysosomes by lysosomal hydrolases.
In blood, it is done by phagocytic cells, particularly by macrophages. Degradation begins with the engulfment of the membranes of white blood cells and erythrocytes.
In brain, where the majority of shingolipids are gangliosides, the turnover is extensive, especially in the neonatal period.
When a lysosomal hydrolase is missing or has submaximal activity, what happens to the intermediates?
What is this class of disorders called? What category of diseases are they classified under?
When one of these enzymes is missing or submaximal in activity, as in some genetic disorders, the respective intermediate is deposited in the lysosomes of the tissue. These disorders are called shingolipidoses that belong to the _lysosomal storage diseases _category.
