-TAGs need to be broken down (solulized) into microscopic micelles before being absorbed into intestinal wall

-This is carrier out by bile salts that are synthesized from cholesterol in the liver, stored in the gallbladder, and released into the small intestine during digestion

(1)-Bile salts act as biological detergents, converting dietary fats into mixed micelles of bile salts and TAGs

(2)- Next, lipase action converts TAGs into monoacylglcerols and diacylglycerols, free FAs, and glycerol.  These products diffuse into the epithelial cells lining the intestines

(3) Then the products are packaged with dietary cholesterol and specific proteins into lipoprotein aggreates called chylomicrons (4)

-Apolipoproteins- are lipid-binding proteins in the blood, responsible for the transport of TAGs, phospholipids, cholesterol adn cholesteryl esters between organs

(5)-Chylomicrons move through the lymphatic system and bloodstream to tissues

(6)-Lipoprotein lipase, activated by apoC-II in the capillary, converts TAGs to FAs and glycerol

(7) Fatty acids enter cells

(8)-Fatty acids are oxidized as fuel or reesterified for storage

(5)-

-Dietary TAGs are broken down via bile salts, formed into lipoproteins (chylomicrons), taken into the blood stream and converted to FAs and glycerol, moved to the cell, then are oxidized as fuel or reesterfied for storage

-TAGs in adipose tissue where they are stored are moved from the lipid droplets to the bloodstream then transporterted to be used in beta-oxidation in a series of steps:

(1)-When low levels of glucose in the blood trigger the relsease of glucagon, the hormone binds its receptor in the adipocyte membrane and

(2) Stimulates adenylyl cyclase, via a G protein, to produce cAMP. 

(3) This activates PKA, which phosphorylates the hormone-sensitive lipase and

(4) Perilipin molecules on the surface of the lipid droplet, where

(5) It hydrolyzes TAGs to free FAs

(6) FAs leave the adipocyte, bind serum albinum in the blood, and are carrierd in the blood; they are released from the albumin and

(7) Enter a myocyte via a specific fatty acid transporter

(8) In the myocyte, FAs are oxidized to CO2, and the energy of oxidation is conserved in ATP, which fuels muscle contraction and other energy-requiring metabolism in the myocyte

The conversation of FA to a fatty acyl-CoA is catalyzed by fatty axyl-CoA synthase and inorganic pyrophosphatase.  Fatty acid activation by formation of the fatty acyl-CoA derivative occurs in two steps.

In step (1), the carboxylate ion displaces the outer two phosphates of ATP to form a fatty acyl-adenylate, the mixed anhydride of a carboxylic acid and a phosphoric acid.  The other product is PPi, an execellent leaving group that is immediately hydrolyzed to two Pi, pulling the reaction in the forward direction

In step (2), the thiol group of coenzyme A carries out nucleophilic attack on the enzyme-bound mixed anhydride, displacing AMP and forming the tioester fatty acyl-CoA. 

Three step process of transferring FAs into the mitochondrion-

-esterification to CoA, transesterfication to carnitine followed by transport, and transesterfication back to CoA

FA entry into the mitochondria via the axyl-carnitine/carnitine transporter: After fatty acyl-carnitine is formed at teh outer membrane of in the intermembrane space, it moves into the matrix by facilitated diffusion through the transporter int eh inner membrane.  In the matrix, the acyl group is transferred to mitochondrial coenzyme A, freeing carnitine to return to the intermembrane space throught the same transporter.  Acyltransferase I is  inhibied by malonyl-CoA, the first inermediate in fatty acid synthesis.  This inhibition prevents the simultaneous synthesis and degradation of fatty acids

The Beta Oxidation of Saturated FAs has Four Steps

First, dehydrogenation of fatty acyl-CoA produces a double bond between the alpha and beta carbon atoms yielding a trans-delta^2-enoyl CoA.

The first step is catalyzed by three isozymes of acyl-CoA dehydrogenase; FAD is the electron acceptor; electrons from the rxn ultimately enter the respiratory chain and pass to O2

(2)

In the second step, water is added to the double bond of the intermediate to form beta-hydroxyacyl-CoA dehydrogenase; This reaction is catalyzed by enoyl-CoA hydratase

(3)

In the third step, the new intermediate is dehydrogenated to form beta-ketoacyl-CoA, by the action of beta-hydroxyacyl-CoA dehydrogenase; NAD+ is the electron acceptor

(4) tHE FOURTH AND LAST STEP OF CYCLE IS CATALYZED BY ACYL-CoA acetyltransferase (thiolase), which promotes reaction of beta-ketoacyl-CoA with a molecule of free coenzyme A to split off the carboyl-terminal two-carbon fragment of the original FA as acetyl-CoA.  The other pdt is the coenzyme A thioester of the FA