Class Notes (806,874)
Canada (492,493)
Biochemistry (200)
BIOCHEM 2EE3 (129)

Lipid Metabolism.docx

7 Pages
Unlock Document

McMaster University
Xudong Zhu

Unit 10 - Lipid Metabolism Fatty acids have four major physiologic roles in the cell:  Building blocks of phospholipids and glycolipids  Added onto proteins to create lipoproteins, which targets them to membrane locations  Fuel molecules - source of ATP  Fatty acid derivatives serve as hormones and intracellular messengers Absorption and Mobilization of Fatty Acids  Most lipids are triacylglycerols, some are phospholipids and cholesterol.  Digestion occurs primarily in the small intestine.  Fat particles are coated with bile salts (amphipathic) from gall bladder.  Degraded by pancreatic lipase (hydrolyzes C-1 and C-3  2 fatty acids and 2- monoacylglycerol).  Can then be absorbed by intestinal epithelial cells; bile salts are recirculated after being absorbed by the intestinal epithelial cells.  In the cells, fatty acids are converted by fatty acyl CoA molecules.  Phospholipids are hydrolyzed by pancreatic phospholipases, primarily phospholipase A . 2  Cholesterol esters are hydrolyzed by esterases to form free cholesterol, which is solubilized by bile salts and absorbed by the cells.  Lipids are transported throughout the body as lipoproteins.  Lipoproteins consist of a lipid (tryacylglycerol, cholesterol, cholesterol ester) core with amphipathic molecules forming layer on outside. Lipoproteins  Both transported in form of lipoprotein particles, which solubilize hydrophobic lipids and contain cell-targeting signals.  Lipoproteins classified according to their densities: o chylomicrons - contain dietary triacylglycerols o chylomicron remnants - contain dietary cholesterol esters o very low density lipoproteins (VLDLs) - transport endogenous triacylglycerols, which are hydrolyzed by lipoprotein lipase at capillary surface o intermediate-density lipoproteins (IDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis and converted to LDLs o low-density lipoproteins (LDL) - contain endogenous cholesterol esters, which are taken up by liver cells via receptor-mediated endocytosis; major carrier of cholesterol in blood; regulates de novo cholesterol synthesis at level of target cell o high-density lipoproteins - contain endogenous cholesterol esters released from dying cells and membranes undergoing turnover 1 Storage of Fatty Acids  Triacylglycerols are transported as chylomicrons and VLDLs to adipose tissue; there, they are hydrolyzed to fatty acids, which enter adipocytes and are esterified for storage.  Mobilization is controlled by hormones, particularly epinephrine, which binds to -adrenergic receptors on adipocyte membrane  protein kinase A activated  phosphorylates hormone- sensitive lipase  converts triacylglycerols to free fatty acids and monoacylglycerols.  Insulin inhibits lipid mobilization (example of reciprocal regulation).  Monoacylglycerols formed are phosphorylated and oxidized to DHAP (intermediate of glycolysis and gluconeogenesis). + + ATP ADP NAD NADH + H glycerol glycerol 3-phosphate dihydroxyacetone phosphate glycerol kinase glycerol phosphate dehydrogenase Can be converted to glucose (gluconeogenesis) or pyruvate (glycolysis) in the liver. Fatty Acid Oxidation (-oxidation)  Fatty acids are degraded by oxidation of the  carbon by -oxidation.  Pathway that removes 2-C units at a time  acetyl CoA  citric acid cycle  ATP  There are three stages in -oxidation: o Activation of fatty acids in cytosol catalyzed by acyl CoA synthetase; two high energy bonds are broken to produce AMP o 2) Transport of fatty acyl CoA into mitochondria via carnitine shuttle o 3) -oxidation - cyclic pathway in which many of the same enzymes are used repeatedly (see pathway sheet) -oxidation of odd chain and unsaturated fatty acids  Odd chain fatty acids undergo -oxidation until propionyl CoA is formed.  Propionyl CoA is then converted to succinyl CoA, which then enters the Krebs cycle.  See pathway sheet for details  Unsaturated fatty acids need two additional enzymes besides those of -oxidation. o enoyl-CoA isomerase o 2,4-dienoyl-CoA reductase  How the pathway looks depends upon the location of the double bond, but there are two possibilities.  See pathway sheets for details. ATP generation from Fatty Acid Oxidation:  Can be estimated from the amount of acetyl CoA, QH , 2nd NADH produced.  See pathway sheet. Regulation of Fatty Acid Oxidation  Already talked about fatty acid mobilization via epinephrine.  Net result is high concentrations of acetyl CoA and NADH via -oxidation.  Both molecules allosterically inhibit pyruvate dehydrogenase complex.  Most of acetyl CoA produced goes to Krebs cycle; during periods of fasting, excess acetyl CoA is produced, too much for Krebs cycle. 2  Also in diabetes, oxaloacetate is used to form glucose by gluconeogenesis --> concentration of oxaloacetate is lowered.  Result is the diversion of acetyl CoA to form acetoacetate and 3-hydroxybutyrate; these two molecules plus acetone are known as ketone bodies.  Acetoacetate is formed via the following reactions: acetyl CoA CoA acetyl CoA 2 acetyl CoA 3-hydroxy- acetoacetate HMG-CoA lyase 3-methylglutaryl CoA + + NADH + H + -hydroxy H NAD butyrate CO 2 Dehydrogenase 3-hydroxybutyrate acetone 
More Less

Related notes for BIOCHEM 2EE3

Log In


Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.