Fatty Acid Catabolism ch. 17.1 and 17.3 Flashcards
How do lipids yield E? Store E?
Through b-oxidation of FA (long chains) OR ketone bodies to get regenerated as Acetyl coA. Both = ATP!
Adipose tissues store FA as Triglycerides
How does b-oxidation of saturated FA occur?
B-oxidation: occurs at carboxyl end.
B-oxidation pathway is FA b-oxidized to– acetyl CoA –TCA– ETC chain
4-step enzyme-catalyzed process of oxidation:
Palmitoyl is a 16 C FA.
1- ACYL-CoA DEHYDROGENASE (along w/ FADH2) will affect C2 (alpha) and C3 (beta). It will take out H to make a double bond between C2-C3.
2- ENOYL-CoA HYDRATASE will used H2O (in the form of OH) to take out double bond and put OH on C3.
3- B-HYDOXYACYL-CoA-DEHYDROGENASE (along w/ NADH) will reduce C3 with NADH so that 2 H are removed and forms a double bond.
4- ACYL-CoA ACETYLTRANSFERASE/thiolase will use CoA-Sh to cleave between C2 and C3. This yields a 14C long FA (16C with 2C less, because of acetyl CoA produced) and acetyl CoA ‘produced’.
5- Repeat. Until the whole palmitoyl FA is all oxidized.
For a 16C FA, b-oxidation only occurs 7 times to cleave 8 acetyl-CoA. Generated 7 FADH2 and 7 NADH (NOT 8). Will yield ATP ultimately.
Why are FA good E source?
FA are highly reduced compounds (more H than OH)
Since C molecules in FA chains are at reduced state it yields more than 2 fold E than CHO and prots.
Since no oxygen is used to catabolize the FA chain, more ATP is produced.
TG are relatively inert– no risk of undesirable reactions
How is osmolarity and lipids linked?
Lipids are insoluble in H2O, which does NOT increase osmolarity (measures osmotic pressure of a solution and det. how well the solvent will diffuse across a semipermeable membrane (osmosis))
How does lipid metabolism occur from mouth to adipose tissues?
1- in s.i., EMULSIFICATION of fats into MICELLES 2- INTESTINAL LIPASES yield DIACYLGLYCEROLS, MONOACYLGLYCEROLS, FREE FA and GLYCEROLS 3- mucosal epithelium absorbs these broken down molecules 4- restructurate broken molecules into CHYLOMICRONS 5-Chylomicrons are thrown out of intestinal syst., IN BLOOD SYST. 6-Chylomicrons release TG in blood. LIPOPROTEIN LIPASES (in capillaries) cleave and help abs. of the FA into the cells. 7- Cells can use FA (oxidized) or store it (REESTERIFICATION = put back FA on glycerols= TG).
What are lipoprotein lipases ?
In capillaries, LIPOPROTEIN LIPASES exist and CLEAVE and ABSORB the TG–FA into the cells.
These are activated by APO(C)-II
What ate apolipoproteins?
Apolipoproteins are LIPID-BINDING PROTS in the
blood, responsible for the MVT of triacylglycerols,
phospholipids, cholesterol, and cholesteryl esters be-
tween organs.
What are chylomicrons made up?
Chylomicrons have apolipoprots, TG, cholesterols, cholesteryl esters, phospholipids. Really big molecule, but low density of cholesterol.
How do lipids get removed from adipose tissue to blood?
Neutral lipids (TG) are stored in adipose tissue in the form of a lipid droplet surrounded with a phospholipid monolayer. This monolayer has PERILIPINS (restricts access to stored TG, when unwanted).
1- When adipocytes release FA, they receive a signal:
GLUCAGON goes to GPCR receptor, activates ADENYLYL CYCLASE, produces cAMP (exctracellular message), activates PKA and phosphorylates perilipins and hormone-sentitive lipase (multiplying hydrolysis effect of TG).
2- The phosphorylated perilipins cause HORMONE-SENSITIVE LIPASE to move from cytosol to the lipid droplet, where it can hydrolyze TG to free FAs and glycerol.
3- The fatty acids thus released by HSL (free
fatty acids, FFA) pass from the adipocyte into the
blood, where they bind to the blood protein SERUM ALBUMIN.
4-Bound to this soluble protein, the (now soluble) insoluble FAs are carried to the tissues. The FAs dissociate from albumin and are moved by PLASMA MEMBRANE TRANSPORTERS into cells to serve as fuel.
Perilipin is normally associated to CGI. How is this relevant for lipid mobilization from adipose tissue to bood?
Perilipins are normally associated to CGI.
- When perilipin is phosphorylated by PKA, CGI58 dissociates and binds to ADIPOSE TG LIPASE, which specifically attacks TG to make diacylglycerol.
- PKA also interacts with hormone sensitive lipase, by phosphorylating it. HSL attacks diacylglycerols made by ATGL, to take out 2nd FA and make a monoacylglycerol.
- MGL (monoacylglycerols lipase) attacks monoacylglycerols, to release last FA into bloodstream.
Serum albumin can bind to know many NEFA (non-esterified FA, which are free FA attached to this prot.)?
10 NEFA
How does insulin and glucagon affect FA metabolism?
Insulin = no more glucagon = store FA Glucagon = no more insulin = release FA
How does glycerol get broken down to yield E? (5% of total TG E)
Glycerol in this whole process lipid mobilization is left out. So, we get Glycerol phosphorylated by GLYCEROL KINASE, then oxidized by G-3-P DEHYDROGENASE, then isomerized by TRIOSE PHOSPHATE ISOMERASE which yields molecule of D-G-3-P to go down glycolysis and get oxidized.
How does FA get activated and transported into the mitochondria occur?
1- FA needs to be activated to move through membrane of mit. The enzyme that activates FA is FATTY ACYL-CoA SYNTHETASE; It uses ATP and attaches Adenosine MONOphosphate (2 phosphate gr are released) to the first C of FA. NOTE: This is not phosphorylation
2- Fatty-acyl-CoA attaches a CoA to monophosphate-adenosine-FA and it releasse monoposhate adenosine from this molecule.
FA are now activated by CoA and can be transported to the mitochondria.
Mitochondria has 2 membranes: outer membrane has CARNITINE ACYLTRANSFERASE 1
1: CA1 removes the CoA and replaces it with carnitine; FA is inactivated.
2: Acyl-carnitine can transport the compound across the membrane, through another transporter on inner layer; has CARNITINE ACYLTRANSFERASE II, which removes carnitine and put back CoA onto molecule of FA.
FA is thus activated in the MATRIX.
Fatty acyl-CoA transferase can also be used for…?
Fatty acyl CoA can also be used to synthesize longer membrane lipids. ???