Fatty Acid Oxidation/Ketogenesis

fatty acid β-oxidation

process in the liver in which free fatty acids are oxidized to at the
β-carbon atom produce acetyl-CoA, NADH, and FADH2

bile salts

amphipathic steroid derivatives with detergent properties, participating in digestion
and absorption of lipids

chylomicrons

a class of lipoproteins that transport lipids from the intestinal cells to the rest of the body

apolipoprotein C-II

lipoprotein lipase cofactor embedded in chylomicrons that catalyzes activity

apolipoproteins

the protein components of lipoproteins

lipoproteins

clusters of lipids associated with proteins that serve as transport vehicles for lipids in the lymph and blood

lipoprotein lipase

an enzyme that sits on the outside of cells and breaks apart triglycerides, so that their fatty acids can be removed and taken up by the cell

hormone-sensitive lipase

an enzyme inside adipose cells that hydrolyzes triglycerides so that their parts (glycerol and fatty acids) are released into circulation and become available to other cells as fuel; sensitive to glucagon and epinephrine

perilipin

protein that coats the lipid droplet in adipocytes and is subject to phosphorylation during the activation of lipolysis

lipid droplets

storage of esterified forms of fatty acids as high energy storage molecules

free fatty acids

the main source of the body's energy during the fasting phase; released from adipose tissue in response to high levels of glucagon

serum albumin

protein in blood that noncovalently binds fatty acids and transports them to target tissues

fatty acyl CoA synthetase

enzyme in the cytosol that activates fatty acids by attaching them to acetyl CoA via thioester bond; uses 2 ATP equivalents of energy (yields AMP)

carnitine shuttle

mechanism for moving fatty acids from the cytosol to the mitochondrial matrix as fatty esters of carnitine

CAT1 (carnitine acetyltransferase I)

enzyme in the outer mitochondrial membrane that catalyzes attachment of fatty acids to carnitine; rate-limiting enzyme of fatty acid oxidation; allosterically inhibited by malonyl-CoA

carnitine

a nonessential, nonprotein amino acid made in the body from lysine that helps transport fatty acids across the mitochondrial membrane

carnitine transporter

transporter that transports fatty acyl-carnitine across the inner mitochondrial membrane

Carnitine acyltransferase 2

enzyme in the inner mitochondrial matrix that transfers fatty acyl group from carnitine back to CoA

first step of beta oxidation (dehydrogenation)

acyl-CoA dehydrogenase uses FAD to form a double bond between α and β carbons of saturated FA; yields FADH2 and an unsaturated intermediate

2nd step of beta oxidation (hydration)

hydration of the double bond by a hydratase to form a hydroxyl group on the β carbon

3rd step of beta oxidation (dehydrogenation)

a dehydrogenase uses NAD+ to take 2 H+ from the fatty acid, yielding NADH and β-ketoacyl-CoA

4th step of beta oxidation (thiolysis)

a thiolase cleaves the bond between α and β carbons forming acetyl-CoA and an acyl-CoA with 2 less carbons

unsaturated fatty acid oxidation (double bond at odd numbered position)

an isomerase changes the position and configuration of the preexisting double bond between the α and β carbons; 1st dehydrogenation is skipped, so 1.5 less ATP are produced

unsaturated fatty acid oxidation (double bond at even numbered position)

a reductase uses NADPH to merge adjacent double bonds, then an isomerase transfers the double bond so that it is between the α and β carbons, allowing oxidation to continue

odd-numbered/branched fatty acid oxidation

glucogenic oxidation that generates propionyl-CoA, which can be converted to succinyl-CoA

propionyl-CoA

produced during the oxidation of odd-chain fatty acids and can be carboxylated and then isomerized into succinyl-CoA, which can then be used to synthesize glucose (via oxaloacetate)

peroxisome oxidation pathway

oxidation pathway used to oxidize fatty acids with more than 20 hydrocarbons; energy derived is used to generate H2O2 instead of ATP

ketogenesis

liver mitochondria produce water-soluble ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) when there is excess acetyl-CoA from fatty acid oxidation

funcitons of ketogenesis

1) remove excess acetyl groups so FAO can continue

2) save CoA for other functions in liver

3) provide extrahepatic tissues with ketone bodies as fuel source

thiolase

in ketogenesis, enzyme that reversibly converts 2 acetyl CoA to acetoacetyl-CoA (in liver) and acetoacetyl-CoA to 2 acetyl-CoA (in extrahepatic tissue)

HMG-CoA synthase

enzyme that attaches acetyl-CoA to acetoacetyl-CoA to form HMG-CoA; rate-limiting enzyme of ketogenesis

HMG-CoA lyase

enzyme that breaks down HMG-CoA into acetoacetate, which can be further broken down into other ketone bodies

beta-ketoacyl-CoA transferase

catalyzes the activation of acetoacetate in extrahepatic tissues by transferring CoA from succinyl-CoA