Lipid MetabolismLipid Metabolism

Dietary Lipid ReactionsDietary Lipid Reactions

Lecture 1 of 5Lecture 1 of 5

Jim Littlejohn

11/20/03

Texas A+M Health Sciences Center:

College of Medicine

Lipid TypesLipid Types

Vitamins A, D, E, KVitamins A, D, E, K Phospholipids, Sphingolipids, Phospholipids, Sphingolipids,

GlycolipidsGlycolipids Fatty Acids and TriacylglycerolsFatty Acids and Triacylglycerols Cholesterols Cholesterols LipoproteinsLipoproteins

• VLDL, LDL, HDLVLDL, LDL, HDL• ChylomicronsChylomicrons

Fatty AcidsFatty Acids hydrophilic vs. hydrophobichydrophilic vs. hydrophobic saturated vs. unsaturatedsaturated vs. unsaturated Essential fatty acidsEssential fatty acids

• PUFA’s (position of first double bond from methyl end)PUFA’s (position of first double bond from methyl end)• ΩΩ-3, -3, ΩΩ-6 Fatty Acids-6 Fatty Acids• Humans can only add from carboxyl to 9Humans can only add from carboxyl to 9thth carbon carbon• Plants can add between 9Plants can add between 9thth and and ΩΩ carbon carbon• Mmmm….Salmon!Mmmm….Salmon!

NomenclatureNomenclature• Described in # of bonds and position of double bonds Described in # of bonds and position of double bonds • arachidonic acid 20:4 arachidonic acid 20:4 ΔΔ5,8,11,145,8,11,14

cis vs. trans cis vs. trans • look at your margarine container!look at your margarine container!

TriglyceridesTriglycerides

Digested in Small IntestineDigested in Small Intestine• needs bile salts (cholesterol skeleton)needs bile salts (cholesterol skeleton)• our only way to excrete cholesterol!our only way to excrete cholesterol!• most are reabsorbedmost are reabsorbed

Pancreatic LipasePancreatic Lipase• breaks into 2-monoacylglycerols and free breaks into 2-monoacylglycerols and free

fatty acids (FFA’s)fatty acids (FFA’s) Absorbed into Intestinal EpitheliumAbsorbed into Intestinal Epithelium Activate FFA’s with CoASHActivate FFA’s with CoASH

• Fatty Acid CoA SynthetaseFatty Acid CoA Synthetase• reassemble triacylglyceridereassemble triacylglyceride

Chylomicrons and VLDLChylomicrons and VLDL Major carriers of triacylglycerols and Major carriers of triacylglycerols and

cholesterolcholesterol Chylomicrons Chylomicrons

• made in intestinal epithelia made in intestinal epithelia • enter lymph to bloodenter lymph to blood• The least protein and most triacylglycerol of The least protein and most triacylglycerol of

the lipoproteinsthe lipoproteins Digested in capillariesDigested in capillaries

• remnants taken up by liverremnants taken up by liver• Lipoprotein LipaseLipoprotein Lipase

VLDL converted to IDL…VLDL converted to IDL…

Fatty acid synthesisFatty acid synthesis Occurs in LiverOccurs in Liver

• Acetyl CoA usedAcetyl CoA used• add in units of 2 carbonsadd in units of 2 carbons

Fatty Acid Synthase Complex (FAS)Fatty Acid Synthase Complex (FAS)• Palmitate, a 16 carbon saturated FAPalmitate, a 16 carbon saturated FA• Converted to other lengths and saturation Converted to other lengths and saturation

states after releasestates after release Packaged in VLDL and sent to bloodPackaged in VLDL and sent to blood

• LDL produced from VLDL and provides LDL produced from VLDL and provides cholesterol to various tissuescholesterol to various tissues

• HDL picks up cholesterol from cells back to HDL picks up cholesterol from cells back to liverliver

Triacylglycerol SynthesisTriacylglycerol Synthesis

Acetyl CoAAcetyl CoA• converted in cytosol to malonyl CoAconverted in cytosol to malonyl CoA• has to get out of matrix!has to get out of matrix!

PyrPyrOAAOAACitrateCitrateOAAOAAMalateMalateMalonyl CoAMalonyl CoA

• NADPH produced by Pentose Phosphate NADPH produced by Pentose Phosphate Pathway and Malic EnzymePathway and Malic Enzyme

LipogenesisLipogenesis• esterification occurs mainly in the liveresterification occurs mainly in the liver• reassembled in intestinal cells and adipocytes!reassembled in intestinal cells and adipocytes!

Transport through the BloodTransport through the Blood ChylomicronsChylomicrons

• lymphlymph blood bloodcapillariescapillariesliver liver • endocytosed and degraded in lysozomeendocytosed and degraded in lysozome• least dense, most triacylglycerolleast dense, most triacylglycerol

VLDLVLDL• used by adipocytes turned into IDLused by adipocytes turned into IDL

IDLIDL• more dense than VLDL, less than ½ triacylglycerolmore dense than VLDL, less than ½ triacylglycerol

LDLLDL• less triacylglycerol and more protein (even more dense)less triacylglycerol and more protein (even more dense)

HDLHDL• lowest triacylglycerol and most proteinlowest triacylglycerol and most protein

AdipocytesAdipocytes

Hormone Sensitive Hormone Sensitive • Lipases activated by glucagon to release Lipases activated by glucagon to release

energy stored in triacylglycerolenergy stored in triacylglycerol Insulin stimulated uptake of glucoseInsulin stimulated uptake of glucose

• adipocytes lack glycerol kinaseadipocytes lack glycerol kinase• DHAP DHAP Glycerol-3-Phosphate Glycerol-3-Phosphate

Metabolic intermediateMetabolic intermediate Lipoprotein LipaseLipoprotein Lipase

• Attached to membranes of cells in the walls of Attached to membranes of cells in the walls of capillariescapillaries

• Apolipoprotein CApolipoprotein CII II activates enzymeactivates enzyme

Oxidation of FA’sOxidation of FA’s

Mainly B-oxidationMainly B-oxidation Transport into mitochondriaTransport into mitochondria

• carnitine carrier systemcarnitine carrier system• even chain completely even chain completely

converted to Acetyl CoAconverted to Acetyl CoA• odd chain fatty acids produce odd chain fatty acids produce

propionyl CoA (used to make propionyl CoA (used to make glucose)glucose)

Beware the trans-fatty acid!Beware the trans-fatty acid!