Lecture 3 (FA catabolism) Flashcards
what is beta oxidation?
4 step enzyme catalyzed process of oxidative removal
what reaction yields energy from FA?
beta oxidation
what are the best storage fuels?
triglycerides (or triacylglyceroles)
yields less than 2 times more energy than CHO and protein
FA chains are highly reduced compounds = has more H than oxygens
what are apolipoproteins?
lipid binding proteins in the blood
responsible for transport of TG, phospholipids, choelsterol and cholesterylesters
apolipoproteins + lipid = ?
lipoprotein
structure of a lipoprotein?
spherical aggregates
- hydrophobic lipids at core
- hydrophillic protein side chains
- lipid head groups at the surface
types of lipoproteins in increasing stability?
chylomicrons VLDL LDL HDL VHDL
what is re-esterification?
attaching 3 FA chains to glycerol to use fats for storage
describe steps that occur after fats are eaten
- bile salts emulsify fats in SI = forms mixed micelles
- intestinal lipases degrade TG
- FA and break down products are taken up by intestinal mucosa = converted into TG
- TG are incorporated with cholesterol and apolipoproteins into chylomicrons
- lipoprotein lipase converts TG to FA and glycerol
- FA enters blood stream
- FA are used as either fuel or re-esterified for storage
what are perilipins?
- proteins that restrict access to lipid droplets
- prevents lipid mobilization
- on surface of lipid droplets (=storage of FA)
what happens when hormone signals are sent for a need for metabolic energy?
- TG stored in adipose are mobilized and transported to tissues
- epinephrine and glucagon are secreted in response to low bood glucose
- enzyme adenylyl cyclase is stimulated in the adipocyte plasma membrane
- cyclic AMP is produce (intracellular second messenger)
- c-AMP triggers changes that open the lipid droplet to lipases which act on TG
- free fatty acids and glycerol are released
what is ATGL?
adipose TG lipase
what is CGI?
comparative gene identification
protein in perilipins
main enzymes in lipid mobilization from storage?
ATGL (adipose TG lipase)
HSL (hormone sensitive lipase)
MG (monoacylglycerol lipase)
what is NEFA
non esterified FA
same as FFA
describe mobilization of TG stored in adipose tissue
- low levels of glucose in blood triggers release of glucagon
- hormone binds its receptor in adipocyte membrane
- adenylyl cyclase is stimulated via G protein = produce cAMP = activates PKA
- HSL is phosphorylated
and the perilipin molecules on surface of lipid droplet - CGI from perilipin is dissociated = CGI activates with ATGL
- triacylglceryols are converted to diacylglycerols
- phosphoryalted perilipin associates with phosphorylated HSL = allows access to surface of lipid droplet
- diacylglycerol is converted to monoacylglycerol
- MGL hydrolyzes monoacylglycerols
- FA leaves the adipocyte and binds serum albumin in blood –> carried into blood –> released from albumin –> enters myocyte
- FA are oxidized to CO2 in mycote
- energy of oxidation is conserved in ATP
what is ATGL? role?
adipose TG lipase
activates CGI (
what is HSL? role?
hormone sensitive lipase
associates with perilipin to allow access to surface of lipid droplet
what is MGL? role?
monoacylglycerol lipase
hydrolyzes monoacylglycerols to fatty acids
how much energy does glycerol contribute to TG?
5%
describe fate of glycerol after FA are used?
- glycerol kinase converts glycerol to L-glycerol-3-phosphate
(uses ATP) - glycerol-3-phosphate dehydrogenase converts to dihydroxyacetone phosphate (reduces HAD+ to NADH and H+)
- triose phosphate isomerase converts to D-Glyceraldehyde-3-phosphate, which enters into glycolysis
3 main enzymes in entry of glycerol into glycolytic pathway?
- glycerol kinase
- glycerol-3-phos dehydrogenase
- triose phosphate iosmerase
what enzyme catalyzes FA to fatty acyl-CoA?
fatty acyl-CoA synthetase and inorganic pyrophosphatase
very exergonic reaction
describe conversion of FA to fatty acyl-CoA
- carboxylate ion is adenylated by ATP - forms fatty acyl adenylate and pyrophosphate, which is immediately hydrolyzed to two phosphate molecules
- thiol group of coenzyme A attacks the acyl-adenylate = displaces AMP and forms thioester fatty acyl CoA
what is pyrophosphate hydrolyzed into?
2 phosphate molecules
where are enzymes of FA oxidation located?
mitochondria
what can fatty acyl CoA be used for?
to synthesize longer membrane lipids
what is carnitine acyltransferase 1?
what happens to the acyl CoA?
it catalyzes transesterification of carnitine to fatty acyl-carnitine on outer membrane of mito.
Acyl CoA passes through pores on outer membrane into intermembrane space. fatty acyl carnitine ester enters matrix by diffusion fron acyl-carnitine transporter of the inner mito membrane
role of carnitine acyltransferase 2?
- on inner face of inner mito membrane
- regenerates fatty acyl CoA and releases it with free carnitine into the matrix. carnitine reenters intermembrane space via actylcarnitine transporter
describe the carnitine shuttle
1st rxn: acyl CoA synthetases catalyze formation of thioester link between FA carboxyl group and thio group of CoA to yield fatty acyl CoA
