Oxidation of Tram Fats. Unsaturated fats with trans double bonds arc commonly re
ID: 180124 • Letter: O
Question
Oxidation of Tram Fats. Unsaturated fats with trans double bonds arc commonly referred to as "trans fats." There has been much discussion about the effects of dietary trans fats on health. In their investigations of the effects of trans fatty acid metabolism on health, Yu and colleagues (2004) showed that a model trans fatty acid was processed differently from Its cis isomer. They used the three related 18-carbon fatty acids shown In Figure 1 to explore the difference In fl oxidation between cis and trans isomers of the same-size fatty acid. The researchers incubated the coenzyme Figure 1. Structures of three fatty acids analyzed A derivative of each acid with rat liver mitochondria for S minutes, then separated the remaining CoA derivatives in each mixture by HPlC (high-performance liquid chromatography). The results are shown in Figure 2, with separate panels for the three experiments. a) Why did Yu and colleagues need to use CoA derivatives rather than the free fatty acids in these experiments? b) Why were no lower molecular weight CoA derivatives found in the reaction with stearoyl-CoA? c) how many rounds of 0 oxidation would be required to convert the oleoyl-CoA and the elaidoyl-CoA to cis-A' tetradecenoyl-CoAand trans-A '-tetradecenoyl CoA. respectively7 Structures shown in Figure 3. There a re two forms of the enzyme CoA dehydrogenase: long-chain acyl-CoA dehydrogenase (ICAD) and very-long-chain acyl-CoA dehydrogenase (V.CAD). Yu and coworkers measured the kinetic parameters of both enzymes. They used the CoA derivatives of three fatty acids: tradescantia CoA (Cu-CoA), cir-A ' middot tetrachloride-CoA (cA'C)4-CoA), and transfer'-tetrachloride-CoA (tA'Cu-CoA). The results are shown in Table 1. (You might need to review kinetic parameters to answer this question Q) d) For LCAD, the C differs grammaticality Adelaide-CoA. Province a plausible explanation for this observation in terms of the structures of the substrate molecules. c) The kinetic parameters of the two enzymes arc relevant to the differential processing of these fatty acids only If the LCAD or VICAD reaction (or both) is the rate-limiting step In the pathway. What evidence Is there to support this assumption? f) How do these different kinetic parameters explain the different levels of the CoA derivatives found after Incubation of rat liver mitochondria with steamroller-CoA, oleo-CoA. and elaidoyl-CoA (shown in the three-panel figure)? Vu and coworkers measured the substrate specificity of rat liver mitochondrial thioesterase, which hydrolyzes acyl-CoA to CoA and free fatty acid. This enzyme was approximately twice as active with C-.t-CoA thioesters as with C-.rCoA thioesters. g) Other research has suggested that free fatty acids can pass through membranes. In their experiments. Yu and colleagues found trans-A -tetradecenoic acid outside mitochondria (i.e., in the medium) that had been incubated with elaidoyl-CoA. Describe the pathway that led to this extra mitochondria I transfer A'-contradiction acid. Be sure to indicate where in the cell the various transformations take place. as well as the enzymes that 1 catalyze the transformations. i) It is often said in the popular press that "trans fats are not broken down by your cells and instead accumulate in your body." In what sense is this statement correct and in what sense is it an over simplificationExplanation / Answer
a. Detailed reactions involved in B-oxidation of fatty acids to form acetyl CoA were worked out by Lynen, Mahler and Green. They found that co-enzyme A present in the cells is necessary for the oxidation of fatty acids and that it participates in the first step of b-oxidation of fatty acis. CoA derivatives of fatty acis are know as fatty acyl derivatives. The fatty acid undergoies series of reactions, leading to the splitting off of acetyl CoA and formation of an acyl CoA derivative containing two carbon atoms less than the initial acyl CoA compound. Repetition of the process shortens the fatty acid chain until it is split into acetyl CoA units.
b. As mentioned above, the CoA derivatives of fatty acids are long before proceeding into the steps of b-oxidation, thus they have higher molecular weight. Thus, they will not be seen together with a low molecular weight compound.
g. This is overcome by allowing acetyl CoA to form citrate in the mitochondria by condensing with oxaloacetate and citrate which is permeable, comes out of the mitochondria into the cytosol. The process is reversed and acetyl CoA is made available in the cytosol by a reaction catalysed by enzyme ATP citrate lyase
Citrate + ATP + CoA -----------> Acetyl CoA + oxaloacetate + ADP + P.
Related Questions
Navigate
Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.