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128 Cards in this Set
- Front
- Back
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How many types of membrane lipids are there and what are they?
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Three.
-Phospholipids -Glycolipids -Cholesterol |
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What is the fourth lipid we talked about that is not found in membranes?
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Triacyglycerol (Triglyceride)
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Additional Lipids in the body include?
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Steroid Hormones
Fatty Acids (FFAs) |
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Functions of lipids
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Energy
Barrier Extracellular messages/signals Intracellular signals (2nd messengers) |
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Fatty Acids are a good source of what?
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AcCoa (Acetyl CoA) for use in TCA cycle (ENERGY PRODUCTION)
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What is the function of Steroid hormones and fatty acid products?
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Extracellular messages/signals
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What is another function of membrane lipid products?
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Intracellular signals (second messengers)
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What is the role of many vitamins?
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Cofactors used by enzymes
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What amount of lipid do adults typically ingest/day?
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60-150grams (90% is triacyglycerol)
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Lipids we ingest include?
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Cholesterol
Cholesterol esters Phospholipids Free Fatty Acids Triacylglycerol |
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What is lingual lipase?
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A salivary enzyme secreted in the saliva that is inactive in adults because it is stable at low pH but active in infants and young children because of their higher gastric pH (doesn't inactivate the enzyme)
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What digestion enzyme is released by the stomach?
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Gastric lipase
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What is the specific function of gastric lipase?
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Active in the duodenum at neutral pH and acts on triacyglycerols with short to medium length FA (like milk fats)
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Where does the majority of lipid digestion occur in adults?
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Small intestine
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In adults why aren't lipids digested before the duodenum?
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Dietary fats are not emulsified before reaching the duodenum even in the presense of lipases. This is due to low SA/Volume.
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Before dietary fats are emulsified what are they like structurally?
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They form globules with low SA/Volume ratio
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Where does emulsification of dietary lipids occur?
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The small intestine
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Why do lipids need to be emulsified?
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They have a small SA/volume ratio and therefore enzymes aren't very effective at digesting the lipids. Once the lipids are emulsified the SA that the enzymes can act on increases dramatically.
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What emulsifies dietary lipids?
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Bile salts derived from Cholesterol from the liver, stored and concentrated in the gallbladder
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What two bile salts does Tim talk about that our bodies use to emulsify dietary lipids?
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Glycocholate & Taurocholate
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What is the hydrophobic portion of a bile salt composed of?
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Cholesterol from the liver
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What is the hydrophilic portion of a bile salt composed of?
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Glycine or Taurine
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What are the bile salts?
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Glycocholate & Taurocholate
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What are the bile acids?
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Cholic acid (cholate)
Chenodeoxycholic acid (chenodeoxycholate) |
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Which are the precursors? Bile acids or bile salts?
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Bile acids are precursors to bile salts
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What are found in bile?
a.) Bile salts b.) Bile acids c.) both |
A. Bile salts (only bile salts are found in bile)
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Which are found in the intestinal lumen?
a.)Bile salts b.)Bile acids c.) both |
C. Both bile salts and acids are found in the lumen of the small intestine. This is because intestinal bacteria can cleave glycine and taurine off of their bile salts. Therefore both the salts from bile and the acids would be present
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Pancreatic enzymes act on?
a.)Emulsified Triacyglyecerides b.)Cholesterol esters c.)Phospholipids d.) all of the above e.) none of the above |
D. All of the above
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Where are pancreatic proenzymes dumped?
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2nd part of duodenum
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Duodenal mucosal cells are stimulated by the presence of lipids and proteins to release what?
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Secretin (a polypeptide hormone)
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What are the most important properties of polypeptide hormones?
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Fast acting
Short lived |
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The pancreas secretes?
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Digestive (pancreatic) enzymes
HCO3- |
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What is the role of CCK ?(Cholecystokinin)
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Stimulate pancreas to release HCO3-, digestive enzymes, stimulate release of bile by gallbladder, reduce motility of stomach (presence of lipids and proteins means longer digestive period needed)
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What is the function of HCO3- released by the pancreas and mucosal cells?
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neutralize duodenal pH (low pH chyme from stomach) so that pancreatic enzymes function properly
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What are the products of carbonic anhydrase?
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HCO3- (Bicarbonate) and H+ [from Co2 and H2O]
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Why can't triglycerides pass through mucosal cell membranes?
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They are too bulky
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What is the function of pancreatic lipase?
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Pancreatic lipase cleaves dietary lipids (triacyglycerides) into (2) FFA's and (1) 2-MAG (2-monoacylglycerol)
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What is the function of pancreatic cholesterol esterase?
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Converts cholesterol esters (CE's) into (1) cholesterol and (1) FFA
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What enzyme activates Phospholipase A2?
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Trypsin
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What is the function of Phophsolipase A2?
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Clips (1) FFA from Phosphatidylcholine
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What is the function of Lysophospholipase?
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Clips the 2nd FFA from the product of Phospholipase yielding Glyceryl-phosphorylcholine (consists of one glycerol, phosphate, and choline)
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What are the products of Lipid catabolism in the small intestine?
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FFA's
Cholesterol 2-MAG (2-monoacyglycerol) (Exist complexed with bile salts in micelles) |
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What is the effect of CCK in the blood?
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Inhibits gastric emptying
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What is the eventual fate of bile acids and salts?
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They are reabsorbed in the Ileum and transported bound to Albumin via the hepatic portal system to be reused by the liver. 15-20g used/day and only ~0.5 g needs to actually be produced de novo.
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What crosses the jejunal mucosal cell membrane?
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FFA
Cholesterol 2-MAG Glycerol Bile Acids Bile Salts? |
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What happens to FA's that have entered a mucosal cell?
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They are converted via Fatty Acyl CoA Synthase or Thiokinases to Fatty Acyl CoA. This step requires a pyrophosphate (using 2 high energy phosphate bonds. equiv. to 2 ATP's)
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What enzyme converts (2) Fatty Acyl CoA & 1 MAG to Triaclglecerol and (2) CoA's?
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AcylTransferase
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What is the function of Acyltransferase?
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Converts (2) Fatty acyl-?CoA units and one MAG (monoacylglycerol) to Triacylglycerol and (2) CoA's
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What is interesting about Acyl Transferase enzymes?
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They are a family of enzymes that make triglycerides. They are also specific for FA chain length. Long chain FFA are added to Triglycerides, short chains are not and enter blood as FFA's and are bound by albumin.
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What is albumin?
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A plasma protein used for transport of FFA's in the context of lipid metabolism.
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Are Triglycerides the only product of Acyl Transferases?
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No, some add FFA's to Cholesterol or Lysophospholipids yielding cholesterol esters and phospholipids.
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What problem do mucosal cells encounter regarding newly reassembled Triglycerides?
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They are highly hydrophobic so they need to be packaged for transport in the aqueous environment of the blood. These packages are referred to as Chylomicrons and are very similar to Micelles. Apolipoprotein B-48 forms a "candy" shell around the chylomicrons allowing them to float freely in the blood stream.
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Where do chylomicrons go after leaving a mucosal cell?
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They are exocytosed and enter the lymphatic system via intestinal lacteals. They then enter circulation at the thoracic duct.
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Where do chylomicrons from the small intestine enter general circulation
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Left lymphatic duct.
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Triacylglycerol in chylomicrons is primarily destined for what?
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*Skeletal muscle
*Adipose tissue Heart Lung Kidney Liver |
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What enzyme breaks down Triacylglycerols (TG)?
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Lipoprotein lipase
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Where is lipoprotein lipase produced?
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Made and secreted by skeletal muscle and adipose cells.
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Where is lipoprotein lipase found specifically?
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Lining the lumen of the mucosal cells of the small intestine where lipid emulsification and absoroption are taking place.
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What is the function of lipoprotein lipase?
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Cleaves TG's within the chylomicron to yield:
(3) FA's (1) Glycerol |
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What is the systemic effect of Lipoprotein lipase?
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Decreases levels of TG's, increases FFA's and increases Glycerol
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Once lipoprotein has produced FFA's and Glycerol where do they go?
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FFA's can diffuse into cells or circulate bound to albumin.
Glycerol is used by the liver for glycolysis or gluconeogenesis Remnants of the chylomicron (ie. CE's, Phospholipids, Apo B48 and a few TG's) are taken up by the liver. |
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What is the purpose of Apolipoproteins?
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Provide structure, function in cell recognition, and assist lipoprotein metabolism
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What happens when lipoproteins "bump" into each other?
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Apolipoproteins are transferred.
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What is the effect of APO CII on lipoprotein lipase?
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APO CII activates lipoprotein lipase
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What is the function of APO E?
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A tag that hepatic receptors recognize
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What is the primary function of a chylomicron?
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Source of FFA's for tissues throughout the body.
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What are HDL's?
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High density lipoproteins. These are "GOOD"
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What are VLDL's?
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Very low density lipoproteins
These are "VERY BAD" in high blood concentrations |
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What are LDL's?
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Low density lipoproteins.
Thses are "BAD" in high blood concentrations |
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What is the function of VLDL's
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Deliver liver-derived FFA's to tissues.
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Where do LDL's originate?
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They are "spent" VLDL's and are leaky and deliver CE (cholesterol) to tissues of the body.
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What is the function of HDL's?
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They scavenge cholesterol and trap it as CE's. They are also a reservoir for APO CII & APO E which can be transferred to VLDL's and chylomicrons. APO CII is needed to release the FFA's from TG's by stimulating lipoprotein lipase
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What is needed to stimulate FFA release from TG's in chylomicrons and VLDL's?
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APO CII
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In terms of lipid metabolism, what is going on with dying cells?
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Dying cells release cholesterol, which is then scavenged by HDL's and taken to liver.
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What is the smallest FA?
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Acetic acid (Acetate) 2:0 structure
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What does De Novo mean?
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From scratch
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Describe Acetic acid structure (acetate)
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2 carbon FA, no unsaturations
(2:0) |
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Describe Propionic acid structure
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3 carbon FA, no unsaturations
(3:0) |
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Describe Butyric Acid structure
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4 carbon FA, no unsaturations
(4:0) |
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What carbon length FA's are commonly found in milk fats?
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Anywhere from 4 to 10 carbons are found in milk fats
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Describe the structure of FA Palmitic acid (palmitate)
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16:0
common in lipids and TG's |
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Describe the structure of FA stearic acid (stearate)
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18:0
common in lipids and TG's |
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Describe the structure of FA Oleic acid (Oleate)
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18:1 (1 unsaturation = 1 c-c double bond)
-common in lipids and TG's |
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Describe the structure of Linoleic acid
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18:2
*Essential FA, we cannot synthesize it |
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Describe the structure of Linolenic acid
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18:3
*Essential FA, body cannot synthesize |
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Describe structure of Arachidonic acid
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20:4
*Made from linoleate, and is a precursor of prostaglandins (Paracrines) |
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List the 9 FA's Tim reviewed
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Acetic Acid 2:0
Propionic Acid 3:0 Butyric Acid 4:0 Palmitic Acid 16:0 Stearic Acid 18:0 Oleic Acid 18:1 Linoleic Acid 18:2 Linolenic Acid 18:3 Arachidonic Acid 20:4 |
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What is the tenth FA that Tim mentioned and describe its carbon structure
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Nervonic acid
20:1 Class of FA known as a cerebroside |
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Where does primary FA synthesis occur?
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Liver and lactating mammary glands
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From what sources do we derive FA's
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Diet, de novo synthesis by the liver.
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Where does FA synthesis occur?
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Mitochondrial matrix
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What enzyme converts AcCoa to Citrate?
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Citrate synthase (Adds OAA and releases CoA)
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Where does the AcCoa for FA synthesis come from?
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Glycolysis or AA Metabolism
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How does Citrate used for FA synthesis leave the mitochondrial matrix?
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By means of a Citrate transporter which is stimulated by High citrate levels in the matrix (meaning that there is enough and should export it to cytosol)
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Citrate is converted to AcCoa in the cytosol in FA synthesis by what enzyme and what else is needed?
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Citrate Lyase.
CoA ATP (ADP + Pi) |
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Where is the cell does FA synthesis occur? (which compartment)
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Cytosol
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When building a FA how many carbons are added at a time and in what form?
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Adding 2 carbons per cycle in the form of AcCoa (but remember Malonyl CoA from brain slicer)
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AcCoa is converted to what by Acetyl CoA Carboxylase?
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Malonyl Coa (also need to add HCO3-, one phosphate from ATP.)
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What is the key regulatory enzyme for FA Synthesis?
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Acetyl CoA Carboxylase
(energizing AcCoA for next reaction) |
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What is important about Acetyl CoA carboxylase in FA synthesis?
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Key regulatory enzyme
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What stimulates the key regulatory enzyme of FA synth?
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Citrate, Insulin
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What inhibits the key regulatory enzyme of FA synth?
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Malonyl CoA
Palmitoyl CoA Epinephrine (The enzyme, Acetyl CoA carboxylase is similar to PDH) |
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What is Biotin?
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Necessary cofactor for holding activated CO2 in FA synth.
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What enzyme converts Malonyl CoA to Malonyl ACP?
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Malonyl Transacylase (switch ACP for CoA)
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what are the CNS effects of benzodiazepines?
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enhancing the inhibitory effects of GABA (produces sedation, anxiolysis), depress the limbic system, thalamus, and hypothalamus, reduce reflex activity resulting in muscle relaxation (spinal cord), mild sedation alone (effective in neonates, geriatric or compromised animals: very young, very old, very sick, loss of inhibitions resulting in excited, anxious, and occasionally aggressive behavior, less reliable sedation than ACP or alpha-2agonists), anticonvulsant
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What does ACP signify
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Acyl carrier protein
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If ACP is seen biochemically what is occuring in cells?
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ACP is a marker for FA synth.
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What is happening if Acyl groups are bound to ACP?
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FA Synthesis
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What is happening if Acyl groups are bound to CoA?
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Catabolism of FA
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What happens in one complete cycle of FA synth from Acetyl CoA to substrate?
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Acetyl CoA is converted to malonyl CoA by AcCoa Carboxylase.
Malonyl CoA is converted to Malonyl ACP by malonyl transacylase This product is then combined with an acetyl-ACP from a separate Acetyl CoA converted by Acetyl Transacylase. forming the first product AcetoAcetyl ACP. AcetoAcetyl ACP is converted to D-3-Hydroxybutyrl ACP by Beta Ketoacyl ACP reductase and using an NADPH + H+. D-3 Hydroxybutyrl ACP is converted to Crotonyl ACP by 3 HA ACP Dehydratase which removes a water. Crotonyl ACP is converted to Butyrl ACP is converted to Butyrl ACP by Enoyl ACP reductase and using another NADPH + H+ |
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How are odd chain length FA's made?
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They are synthesized the same way as even but at some point the acetyl transacetylase, Propionyl CoA, a 3 carbon structure is added.
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How many NADPH + H+ are used per cycle of FA synth?
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2
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What is they typical final product of FA synthesis?
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Palmitate (16 carbon FA)
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How many ATP's are consumed going from Acetyl CoA to FA per cycle?
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1 ATP is used (1 high energy P)
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Where is the NADPH that is used in FA synthesis coming from?
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We get 2 NADPH per G6P that we send through the pentose phosphate shunt. We can also get it from the conversion of Malate to Pyruvate by Malic enzyme (Malate DH ) CO2 is produced in the process as well. This process is taking place in the cytosol, the pyruvate is then shuttled to the mitochondrial matrix where it can become AcCoA
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In making Palmitate (a FA) what is the NADPH, ATP count?
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8 AcCoA are required, so 8 NADPH are needed. As well as 7 ATP. 7 HCO3- are also required.
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How do we make longer chain and unsaturated FA's if Palmitate is the major product of FA synth?
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Palmitate is sent to the mitochondria or to microsomes on the ER, enzymes there add Malonyl CoA to carboxyl end to elongate them. C-C double bonds are made by oxidases which require O2 and NADH
NOTE: Linoleic and Linolenis acids are essential because they contain c=c's beyond C10 and our oxidases cant go beyond 9. |
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What are the components of a TG (Triglyceride)?
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Glycerol backbone and the FA's (one is saturated, one is unsaturated, and the third can be either)
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Where does the majority of de novo TG synthesis occur?
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LIVER, but also some occurs in adipocytes
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How do we synthesize glycerol?
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DHAP from glycolysis can be converted to Glycerol-PO4 by Gly-PO4 DH (using an NADH)
OR: GK (Glycerol kinase) can create gly-po4 using on ATP) |
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What must first happen to FA's before they are added to the glycerol backbone?
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They must be activated so that they will react. This is acomplished by FA Acyl CoA synthase (or thiokinase) and uses a CoA and a PPi (pyrophosphate)
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FA CoA and Glycerol-PO4 are combined via which enzyme?
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Acyl transferase, this yields Lysophosphatidate
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What is the function of Acytransferase in TG synthesis?
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Adds a FA to Lysophosphatidate in the form of FA-CoA yeilding Phosphatidate (the simplest phospholipid)
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What is the simplest phospholipid (PL)?
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Phosphatidate
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What is the function of Phosphatase?
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Converts the simplest PL Phosphatidate to Diacyl glycerol by removing a Pi and adding H2O.
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What is interesting about Diacylglycerol?
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It is a second messenger
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What is the function of the enzyme acyltransferase in the last step of TG synthesis?
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Adds the 3rd FA to Diacylglycerol yeilding Triacylglycerol (TG) which is then stored in liver, or packaged in VLDL's for export to body.
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What happens to TG's after synthesis?
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They are stored in the liver or packaged into VLDL's
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