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Passage Whole Grains Have Been Shown to Reduce the Risk of of Cardiovascular

Question 278

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Whole grains have been shown to reduce the risk of cardiovascular disorders.  A team of scientists discovered that the compound 5-aminovaleric acid betaine (5-AVAB) was present at high levels in cardiomyocytes of mice given a diet rich in whole grains and decided to investigate its role in metabolism.  Preliminary evidence indicated that 5-AVAB did not alter the citric acid cycle in these cardiomyocytes, but that it did alter fatty acid metabolism.The plasma membrane transport protein organic cation/carnitine transporter 2 (OCTN2) transports extracellular L-carnitine into the cell against its concentration gradient using the energy provided by the simultaneous transport of Na+ into the cell.  Cellular L-carnitine is required for the transport of fatty acids from the cytosol into the mitochondria.  Based on the structures of 5-AVAB and L-carnitine (Figure 1) , scientists hypothesized that 5-AVAB may interfere with OCTN2-mediated transport of L-carnitine.
Passage Whole grains have been shown to reduce the risk of cardiovascular disorders.  A team of scientists discovered that the compound 5-aminovaleric acid betaine (5-AVAB)  was present at high levels in cardiomyocytes of mice given a diet rich in whole grains and decided to investigate its role in metabolism.  Preliminary evidence indicated that 5-AVAB did not alter the citric acid cycle in these cardiomyocytes, but that it did alter fatty acid metabolism.The plasma membrane transport protein organic cation/carnitine transporter 2 (OCTN2)  transports extracellular L-carnitine into the cell against its concentration gradient using the energy provided by the simultaneous transport of Na<sup>+</sup> into the cell.  Cellular L-carnitine is required for the transport of fatty acids from the cytosol into the mitochondria.  Based on the structures of 5-AVAB and L-carnitine (Figure 1) , scientists hypothesized that 5-AVAB may interfere with OCTN2-mediated transport of L-carnitine.    <strong>Figure 1</strong>  Structures of L-carnitine and 5-AVABTo test their hypothesis, scientists incubated mouse cardiomyocytes with various concentrations of 5-AVAB for 24 hours.  Cells were then provided with the fatty acid palmitate for energy and were deprived of all other energy sources.  The cardiomyocytes were also given 50 μM L-carnitine (endogenous extracellular concentration)  or 2 mM L-carnitine, and the rate of oxygen consumption was monitored (Figure 2) .    <strong>Figure 2</strong>  Oxygen consumption rate of cardiomyocytes at various concentrations of 5-AVAB and L-carnitineIn a follow-up experiment, the scientists used siRNA to silence expression of OCTN2 and found that intracellular L-carnitine levels were similarly depleted in siRNA-treated cells as in cells treated with 100 μM 5-AVAB. Adapted from Kärkkäinen O, Tuomainen T, Koistinen V, et al. Whole grain intake associated molecule 5-aminovaleric acid betaine decreases ß-oxidation of fatty acids in mouse cardiomyocytes. Sci Rep. 2018;8(1) :13036. -Under which of the conditions tested in Figure 2 would cardiomyocytes have the highest ADP/ATP ratio? A) 0 μM 5-AVAB and 50 μM L-carnitine B) 15 μM 5-AVAB and 50 μM L-carnitine C) 100 μM 5-AVAB and 50 μM L-carnitine D) 100 μM 5-AVAB and 2 mM L-carnitine Figure 1  Structures of L-carnitine and 5-AVABTo test their hypothesis, scientists incubated mouse cardiomyocytes with various concentrations of 5-AVAB for 24 hours.  Cells were then provided with the fatty acid palmitate for energy and were deprived of all other energy sources.  The cardiomyocytes were also given 50 μM L-carnitine (endogenous extracellular concentration) or 2 mM L-carnitine, and the rate of oxygen consumption was monitored (Figure 2) .
Passage Whole grains have been shown to reduce the risk of cardiovascular disorders.  A team of scientists discovered that the compound 5-aminovaleric acid betaine (5-AVAB)  was present at high levels in cardiomyocytes of mice given a diet rich in whole grains and decided to investigate its role in metabolism.  Preliminary evidence indicated that 5-AVAB did not alter the citric acid cycle in these cardiomyocytes, but that it did alter fatty acid metabolism.The plasma membrane transport protein organic cation/carnitine transporter 2 (OCTN2)  transports extracellular L-carnitine into the cell against its concentration gradient using the energy provided by the simultaneous transport of Na<sup>+</sup> into the cell.  Cellular L-carnitine is required for the transport of fatty acids from the cytosol into the mitochondria.  Based on the structures of 5-AVAB and L-carnitine (Figure 1) , scientists hypothesized that 5-AVAB may interfere with OCTN2-mediated transport of L-carnitine.    <strong>Figure 1</strong>  Structures of L-carnitine and 5-AVABTo test their hypothesis, scientists incubated mouse cardiomyocytes with various concentrations of 5-AVAB for 24 hours.  Cells were then provided with the fatty acid palmitate for energy and were deprived of all other energy sources.  The cardiomyocytes were also given 50 μM L-carnitine (endogenous extracellular concentration)  or 2 mM L-carnitine, and the rate of oxygen consumption was monitored (Figure 2) .    <strong>Figure 2</strong>  Oxygen consumption rate of cardiomyocytes at various concentrations of 5-AVAB and L-carnitineIn a follow-up experiment, the scientists used siRNA to silence expression of OCTN2 and found that intracellular L-carnitine levels were similarly depleted in siRNA-treated cells as in cells treated with 100 μM 5-AVAB. Adapted from Kärkkäinen O, Tuomainen T, Koistinen V, et al. Whole grain intake associated molecule 5-aminovaleric acid betaine decreases ß-oxidation of fatty acids in mouse cardiomyocytes. Sci Rep. 2018;8(1) :13036. -Under which of the conditions tested in Figure 2 would cardiomyocytes have the highest ADP/ATP ratio? A) 0 μM 5-AVAB and 50 μM L-carnitine B) 15 μM 5-AVAB and 50 μM L-carnitine C) 100 μM 5-AVAB and 50 μM L-carnitine D) 100 μM 5-AVAB and 2 mM L-carnitine Figure 2  Oxygen consumption rate of cardiomyocytes at various concentrations of 5-AVAB and L-carnitineIn a follow-up experiment, the scientists used siRNA to silence expression of OCTN2 and found that intracellular L-carnitine levels were similarly depleted in siRNA-treated cells as in cells treated with 100 μM 5-AVAB.
Adapted from Kärkkäinen O, Tuomainen T, Koistinen V, et al. Whole grain intake associated molecule 5-aminovaleric acid betaine decreases ß-oxidation of fatty acids in mouse cardiomyocytes. Sci Rep. 2018;8(1) :13036.
-Under which of the conditions tested in Figure 2 would cardiomyocytes have the highest ADP/ATP ratio?


A) 0 μM 5-AVAB and 50 μM L-carnitine
B) 15 μM 5-AVAB and 50 μM L-carnitine
C) 100 μM 5-AVAB and 50 μM L-carnitine
D) 100 μM 5-AVAB and 2 mM L-carnitine

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