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Passage The Sirtuins Are a Class of Enzymes That Regulate Various

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The sirtuins are a class of enzymes that regulate various metabolic processes by removing post-translational modifications from enzymes.  SIRT4 is an autosomally encoded sirtuin protein that colocalizes with the pyruvate dehydrogenase complex.  It deacylates lysine residues on certain metabolic proteins by removing methylglutaryl and hydroxymethylglutaryl units.  Methylglutaryl-CoA and hydroxymethylglutaryl-CoA are intermediates in leucine catabolism, and scientists hypothesized that SIRT4 regulates this pathway.  To test their hypothesis, livers from wild-type (WT) and SIRT4 knockout (KO) mice were treated with α-keto acid derivatives of several amino acids, including the derivative of leucine, α-ketoisocaproate (αKIC) .  Figures 1 and 2 show the rate of oxidation of α-keto acids and oxygen consumption in both WT and KO livers, respectively.
Passage The sirtuins are a class of enzymes that regulate various metabolic processes by removing post-translational modifications from enzymes.  SIRT4 is an autosomally encoded sirtuin protein that colocalizes with the pyruvate dehydrogenase complex.  It deacylates lysine residues on certain metabolic proteins by removing methylglutaryl and hydroxymethylglutaryl units.  Methylglutaryl-CoA and hydroxymethylglutaryl-CoA are intermediates in leucine catabolism, and scientists hypothesized that SIRT4 regulates this pathway.  To test their hypothesis, livers from wild-type (WT) and SIRT4 knockout (KO) mice were treated with α-keto acid derivatives of several amino acids, including the derivative of leucine, α-ketoisocaproate (αKIC) .  Figures 1 and 2 show the rate of oxidation of α-keto acids and oxygen consumption in both WT and KO livers, respectively. <strong>Figure 1</strong>  Box plot showing the rate of oxidation of α-ketoisocaproate (αKIC) , α-ketoglutarate (αKG) , and pyruvate in SIRT4 knockout livers (Note: Asterisk indicates p < 0.05 relative to WT level) <strong>Figure 2</strong>  Oxygen consumption in WT and KO livers in the presence and absence of succinate and reduced cytochrome C (Cyt-C) Because leucine is known to regulate insulin secretion, scientists injected WT and KO mice with leucine and measured plasma insulin levels over time.  They then injected mice with insulin and monitored blood glucose levels (Figure 3) . <strong>Figure 3</strong>  (A) Plasma insulin levels after injection with leucine and (B) blood glucose levels after injection with insulin in both WT and KO mice Adapted from Anderson KA, Huynh FK, Fisher-Wellman K, et al. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017;25(4) :838-855.e15. -Based on the passage, the SIRT4 protein most likely contains which of the following? A) A nuclear localization sequence B) A polyubiquitin tag C) An N-linked carbohydrate chain D) A mitochondrial target signal Figure 1  Box plot showing the rate of oxidation of α-ketoisocaproate (αKIC) , α-ketoglutarate (αKG) , and pyruvate in SIRT4 knockout livers (Note: Asterisk indicates p < 0.05 relative to WT level)
Passage The sirtuins are a class of enzymes that regulate various metabolic processes by removing post-translational modifications from enzymes.  SIRT4 is an autosomally encoded sirtuin protein that colocalizes with the pyruvate dehydrogenase complex.  It deacylates lysine residues on certain metabolic proteins by removing methylglutaryl and hydroxymethylglutaryl units.  Methylglutaryl-CoA and hydroxymethylglutaryl-CoA are intermediates in leucine catabolism, and scientists hypothesized that SIRT4 regulates this pathway.  To test their hypothesis, livers from wild-type (WT) and SIRT4 knockout (KO) mice were treated with α-keto acid derivatives of several amino acids, including the derivative of leucine, α-ketoisocaproate (αKIC) .  Figures 1 and 2 show the rate of oxidation of α-keto acids and oxygen consumption in both WT and KO livers, respectively. <strong>Figure 1</strong>  Box plot showing the rate of oxidation of α-ketoisocaproate (αKIC) , α-ketoglutarate (αKG) , and pyruvate in SIRT4 knockout livers (Note: Asterisk indicates p < 0.05 relative to WT level) <strong>Figure 2</strong>  Oxygen consumption in WT and KO livers in the presence and absence of succinate and reduced cytochrome C (Cyt-C) Because leucine is known to regulate insulin secretion, scientists injected WT and KO mice with leucine and measured plasma insulin levels over time.  They then injected mice with insulin and monitored blood glucose levels (Figure 3) . <strong>Figure 3</strong>  (A) Plasma insulin levels after injection with leucine and (B) blood glucose levels after injection with insulin in both WT and KO mice Adapted from Anderson KA, Huynh FK, Fisher-Wellman K, et al. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017;25(4) :838-855.e15. -Based on the passage, the SIRT4 protein most likely contains which of the following? A) A nuclear localization sequence B) A polyubiquitin tag C) An N-linked carbohydrate chain D) A mitochondrial target signal Figure 2  Oxygen consumption in WT and KO livers in the presence and absence of succinate and reduced cytochrome C (Cyt-C) Because leucine is known to regulate insulin secretion, scientists injected WT and KO mice with leucine and measured plasma insulin levels over time.  They then injected mice with insulin and monitored blood glucose levels (Figure 3) .
Passage The sirtuins are a class of enzymes that regulate various metabolic processes by removing post-translational modifications from enzymes.  SIRT4 is an autosomally encoded sirtuin protein that colocalizes with the pyruvate dehydrogenase complex.  It deacylates lysine residues on certain metabolic proteins by removing methylglutaryl and hydroxymethylglutaryl units.  Methylglutaryl-CoA and hydroxymethylglutaryl-CoA are intermediates in leucine catabolism, and scientists hypothesized that SIRT4 regulates this pathway.  To test their hypothesis, livers from wild-type (WT) and SIRT4 knockout (KO) mice were treated with α-keto acid derivatives of several amino acids, including the derivative of leucine, α-ketoisocaproate (αKIC) .  Figures 1 and 2 show the rate of oxidation of α-keto acids and oxygen consumption in both WT and KO livers, respectively. <strong>Figure 1</strong>  Box plot showing the rate of oxidation of α-ketoisocaproate (αKIC) , α-ketoglutarate (αKG) , and pyruvate in SIRT4 knockout livers (Note: Asterisk indicates p < 0.05 relative to WT level) <strong>Figure 2</strong>  Oxygen consumption in WT and KO livers in the presence and absence of succinate and reduced cytochrome C (Cyt-C) Because leucine is known to regulate insulin secretion, scientists injected WT and KO mice with leucine and measured plasma insulin levels over time.  They then injected mice with insulin and monitored blood glucose levels (Figure 3) . <strong>Figure 3</strong>  (A) Plasma insulin levels after injection with leucine and (B) blood glucose levels after injection with insulin in both WT and KO mice Adapted from Anderson KA, Huynh FK, Fisher-Wellman K, et al. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017;25(4) :838-855.e15. -Based on the passage, the SIRT4 protein most likely contains which of the following? A) A nuclear localization sequence B) A polyubiquitin tag C) An N-linked carbohydrate chain D) A mitochondrial target signal Figure 3  (A) Plasma insulin levels after injection with leucine and (B) blood glucose levels after injection with insulin in both WT and KO mice
Adapted from Anderson KA, Huynh FK, Fisher-Wellman K, et al. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion. Cell Metab. 2017;25(4) :838-855.e15.
-Based on the passage, the SIRT4 protein most likely contains which of the following?


A) A nuclear localization sequence
B) A polyubiquitin tag
C) An N-linked carbohydrate chain
D) A mitochondrial target signal

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