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BIOC13H3 (52)
Daman Bawa (12)
Lecture 10

BIOC13Winter2013 Lecture 10 Notes.docx

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Biological Sciences
Daman Bawa

BIOC13Winter2013 Lecture 10: Intro to Lipid Metabolism Lipid Metabolism in Animals o There are 3 basic sources of fatty acids in animals that can be used for energy conversion processes: o 1) fatty acids present in triacylglycerols obtained from diet o 2) fatty acids stored as triacylglycerols in adipose tissue that are released by hydrolysis following hormone stimulation (glucagon or epinephrine signaling) o 3) fatty acids synthesized in the liver from excess carbohydrates and exported as triacylglycerols Lipid/Fat Storage o fat is stored in adipocytes o obesity can be due to both more cells and increase storage per cell o onset of old age, and reduced metabolic rates = storing more fat per cell; and can also add more cells Fatty acids and physiology o used as fuel and stored as triacylglycerols in adipose tissue  during rest or moderate exercise o acts as building blocks of phospholipids and glycolipids which are impotant components of membranes o covalently attached to many proteins which targets the proteins to membrane locations o fatty acid derivatives serve as hormones and intracellular messengers Transport and storage of fatty acids and triacylglycerols o most of triglycerol stored in adipose tissue originates from dietary lipids o fats that enter the small intersine from the stomach are insoluble and must be emulsified by bile acids such as glycocholate  secreted by the bile duct and function as detergents to promote the formation of micelles o lipases are water soluble enzymes in small intestine that hydrolyze the acyl ester bonds in triacylglycerols to liberate free fatty acids which then pass through the membranse on the luminal side of intestinal epithelial cells o pancreatic lipase cleaves the ester bond at C1 and C3 to release 2 free fatty acids and a monoacylglycerol o dietary lipid transport  chylomicrons o endogenous lipid transport via lipoproteins  VLDL, IDL, LDL , HDL o Free Fatty Acids (FFAs)  derived from TAG hydrolysis in adipocytes o Associate with serum albumin for transport in circulatory system o Chylomicrons transport triacylglycerols to adipose tissue for storage and to muscle cells for energy conversion processes o Apolopoprotein CII on the urface of chylomicrons binds to and activates lipoprotein lipase on endothelial cells = releae of fatty acids and glycerol o Fatty acids diffuse into endothelial cells and then enter nearby adipose and muscle cells o Glycerol produced by lipoprotein lipase returns to the liver where it is converted to dihydroxyacetone phosphate o Truglycerides and cholesterol esters are nonpolar molecules = insoluble o So they are packaged within a polar shell and combine with non polar lipids w amphipathic lipids o Contains protin ligands and scaffolds o Types of lipoproteins o Very Low Density (VLDL) o Intermediate density (IDL) o Low density (LDL) o High density (HDL) o Chylomicrons are 85% TAGS and 2% protein, while HDL is 33% protein and 8% TAGS o (LARGE)Chylomicron > VLDL > IDL >LDL >HDL (SMALL) *in terms of %TAGS o note: the smaller and the higher the protein content, the more dense the lipoprotein Lipid mobilization and metabolism is hormonally regulated  glucagon, epinephrine, thyroxine, insulin and glucocorticoids o hormone in the pic = glucagon and epinephrine Fatty acid oxidation o activation  acyl CoA synthetase (thiokinase) o transport into mitochondria  acylcarnitine transferase/acylcarnitine translocase o beta oxidation cycle  acyl CoA dehydrogenase, enoyl CoA hydratase, L-3-hydroxy CoA dehydrogenase, thiolase Fatty acid oxidation (extra info to go with drawn diagram) o Acyl-CoA synthetase (cytoplasmic) condenses fatty acids with CoA, with hydrolysis of ATP to AMP and PPi o Carnitine carries fatty acyl groups across the IMM  short chain carried directly into matrix, long chain are converted to acyl carnitines and then transported in the cell o Acyl- CoA esters exchanged from acyl carnitine o Acyl carnitine crosses MM o Acyl coa esters formed inside the IMM B oxidation leads large amounts of ATP o Once the electron rich carbons of faty acids are moved into the mitochondrial matrix, their high energy redox potential is traded in for a substantial payout of ATP o The energy conversion process of FA  ATP involves oxidation of fatty acids by sequential degradation of C2 units leading to the generation of FADH2, NADH, and acetyl CoA o The subsequent oxidation of these reaction produced by the citrate cycle and oxidative phosphorylation generates large amount of ATP o Knoop theory  Fas degraded by removal of 2C units at a time o Lehniger shoewed this occurred in mitochondria o Lynen and Reichart showed that the 2C unit released is acetyl CoA o Process begins with oxidation of the C that is beta to the carboxyl carbon = process called beta-oxidation o Repeat sequence of 4 reactions o Strategy  create a carbonyl group on the Be
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