Why liver homogenate cannot oxidize fatty acids unless some atp is present?
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The fatty acid components of triacylglycerols furnish a large fraction of the oxidative energy in animals. Triacylglycerols ingested in the diet are emulsified in the small intestine by bile salts, hydrolyzed by intestinal lipases, absorbed by intestinal epithelial cells and reconverted into triacylglycerols, then formed into chylomicrons by combination with specific apolipoproteins. Chylomicrons deliver triacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue of vertebrate animals are mobilized by the action of hormones through a hormone-sensitive triacylglycerol lipase. The fatty a,cids released by this enzyme bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel.
Once inside cells, free fatty acids are activated at the outer mitochondrial membrane by esterification with coenzyme A to form fatty acyl-CoA thioesters. These are converted into fatty acylcarnitine esters, which are carried by a specific transporter across the inner mitochondrial membrane into the matrix, where fatty acyl-CoA esters are formed again. All subsequent steps in the oxidation of fatty acids take place in the form of their coenzyme A thioesters, within the mitochondrial matrix.
In the first stage of fatty acid β oxidation, four reactions are required to remove each acetyl-CoA unit from the carboxyl end of saturated fatty acylCoAs: (1) dehydrogenation of the α and β carbons (C-2 and C-3) by FAD-linked acyl-CoA dehydrogenases, (2) hydration of the resulting trans-Δ2 double bond by enoyl-CoA hydratase, (3) dehydrogenation of the resulting L-β-hydroxyacyl-CoA by NADlinked β-hydroxyacyl-CoA dehydrogenase, and (4) CoA-requiring cleavage by thiolase of the resulting β-ketoacyl-CoA to form acetyl-CoA and the coenzyme A thioester of the original fatty acid, shortened by two carbons. The shortened fatty acyl-CoA can then reenter the sequence, with loss of another acetyl-CoA. For example, the 16-carbon palmitate yields altogether eight molecules of acetyl-CoA, which in the second stage of fatty acid oxidation can be oxidized to CO2 via the citric acid cycle. A large fraction of the theoretical yield of free energy from fatty acid oxidation is recovered as ATP by oxidative phosphorylation, the third and final stage of the oxidative pathway.
Oxidation of unsaturated fatty acids requires the action of two additional enzymes: enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. Oddcarbon fatty acids are oxidized by the same path
way but yield one molecule of propionyl-CoA. The latter is carboxylated to methylmalonyl-CoA, which is isomerized to succinyl-CoA by a reaction catalyzed by methylmalonyl-CoA mutase. This enzyme requires coenzyme Bl2, a complex cofactor containing a cobalt ion in a corrin ring system. Coenzyme B12 is involved in a number of enzymecatalyzed reactions in which a hydrogen atom is exchanged with a functional group attached to an adjacent carbon.
Fatty acid oxidation is tightly regulated. High carbohydrate intake suppresses fatty acid oxidation in favor of fatty acid biosynthesis.
Peroxisomes of plants and animals, and glyoxysomes in germinating seeds, carry out β oxidation by four steps similar to those occurring in mitochondria. The first oxidation step transfers electrons directly to O2, generating Hz02; no energy is conserved, and the potentially damaging H2O2 is destroyed by catalase. In glyoxysomes, β oxidation serves to convert stored lipids into four-carbon compounds (via the glyoxylate cycle); these compounds are precursors of a variety of intermediates and products required during seed germination.
The ketone bodies acetoacetate, D-β-hydroxybutyrate, and acetone are formed in the liver and are carried to other tissues, where they serve as fuel molecules, being oxidized to acetyl-CoA and thus entering the citric acid cycle. The overproduction of ketone bodies in uncontrolled diabetes or severe starvation can lead to acidosis or ketosis.
Once inside cells, free fatty acids are activated at the outer mitochondrial membrane by esterification with coenzyme A to form fatty acyl-CoA thioesters. These are converted into fatty acylcarnitine esters, which are carried by a specific transporter across the inner mitochondrial membrane into the matrix, where fatty acyl-CoA esters are formed again. All subsequent steps in the oxidation of fatty acids take place in the form of their coenzyme A thioesters, within the mitochondrial matrix.
In the first stage of fatty acid β oxidation, four reactions are required to remove each acetyl-CoA unit from the carboxyl end of saturated fatty acylCoAs: (1) dehydrogenation of the α and β carbons (C-2 and C-3) by FAD-linked acyl-CoA dehydrogenases, (2) hydration of the resulting trans-Δ2 double bond by enoyl-CoA hydratase, (3) dehydrogenation of the resulting L-β-hydroxyacyl-CoA by NADlinked β-hydroxyacyl-CoA dehydrogenase, and (4) CoA-requiring cleavage by thiolase of the resulting β-ketoacyl-CoA to form acetyl-CoA and the coenzyme A thioester of the original fatty acid, shortened by two carbons. The shortened fatty acyl-CoA can then reenter the sequence, with loss of another acetyl-CoA. For example, the 16-carbon palmitate yields altogether eight molecules of acetyl-CoA, which in the second stage of fatty acid oxidation can be oxidized to CO2 via the citric acid cycle. A large fraction of the theoretical yield of free energy from fatty acid oxidation is recovered as ATP by oxidative phosphorylation, the third and final stage of the oxidative pathway.
Oxidation of unsaturated fatty acids requires the action of two additional enzymes: enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase. Oddcarbon fatty acids are oxidized by the same path
way but yield one molecule of propionyl-CoA. The latter is carboxylated to methylmalonyl-CoA, which is isomerized to succinyl-CoA by a reaction catalyzed by methylmalonyl-CoA mutase. This enzyme requires coenzyme Bl2, a complex cofactor containing a cobalt ion in a corrin ring system. Coenzyme B12 is involved in a number of enzymecatalyzed reactions in which a hydrogen atom is exchanged with a functional group attached to an adjacent carbon.
Fatty acid oxidation is tightly regulated. High carbohydrate intake suppresses fatty acid oxidation in favor of fatty acid biosynthesis.
Peroxisomes of plants and animals, and glyoxysomes in germinating seeds, carry out β oxidation by four steps similar to those occurring in mitochondria. The first oxidation step transfers electrons directly to O2, generating Hz02; no energy is conserved, and the potentially damaging H2O2 is destroyed by catalase. In glyoxysomes, β oxidation serves to convert stored lipids into four-carbon compounds (via the glyoxylate cycle); these compounds are precursors of a variety of intermediates and products required during seed germination.
The ketone bodies acetoacetate, D-β-hydroxybutyrate, and acetone are formed in the liver and are carried to other tissues, where they serve as fuel molecules, being oxidized to acetyl-CoA and thus entering the citric acid cycle. The overproduction of ketone bodies in uncontrolled diabetes or severe starvation can lead to acidosis or ketosis.
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