Passage
Synthesis of coenzyme A (CoA) requires vitamin B₅ as a substrate. In bacteria, vitamin B₅ is synthesized by condensation of β-alanine and pantoic acid. β-alanine is produced by decarboxylation of L-aspartate, mediated by the enzyme aspartate α-decarboxylase (ADC) . Active ADC is formed when its inactive precursor, PanD, binds to a regulatory complex composed of acetyl coenzyme A (AcCoA) and a protein known as PanZ. Formation of the PanD-PanZ-AcCoA complex causes the activation loop of PanD to fold into a β-pleated sheet, resulting in PanD autocleavage. Researchers hypothesize that this conformational change allows the Thr57 residue to cleave the N-terminal end of PanD to form ADC.The limited information on the role of PanZ in the synthesis of CoA has stimulated an investigation of its effect on ADC activity. Escherichia coli cells were provided with varying concentrations of PanZ, and the rate of β-alanine production was measured in three different conditions (Figure 1) . Reaction vessels were maintained at pH 6 to ensure optimal decarboxylation activity.
Figure 1 Catalytic activity of ADC in E. coli with increasing concentrations of L-aspartate
Adapted from Monteiro DC, Patel V, Bartlett CP, et al. The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A. Chem Biol. 2015;22(4) :492-503.
-In E. coli, high levels of CoA lead to decreased β-alanine synthesis. This is an example of:

Question

Passage
Synthesis of coenzyme A (CoA) requires vitamin B₅ as a substrate. In bacteria, vitamin B₅ is synthesized by condensation of β-alanine and pantoic acid. β-alanine is produced by decarboxylation of L-aspartate, mediated by the enzyme aspartate α-decarboxylase (ADC) . Active ADC is formed when its inactive precursor, PanD, binds to a regulatory complex composed of acetyl coenzyme A (AcCoA) and a protein known as PanZ. Formation of the PanD-PanZ-AcCoA complex causes the activation loop of PanD to fold into a β-pleated sheet, resulting in PanD autocleavage. Researchers hypothesize that this conformational change allows the Thr57 residue to cleave the N-terminal end of PanD to form ADC.The limited information on the role of PanZ in the synthesis of CoA has stimulated an investigation of its effect on ADC activity. Escherichia coli cells were provided with varying concentrations of PanZ, and the rate of β-alanine production was measured in three different conditions (Figure 1) . Reaction vessels were maintained at pH 6 to ensure optimal decarboxylation activity.

Passage Synthesis of coenzyme A (CoA) requires vitamin B<sub>5</sub> as a substrate. In bacteria, vitamin B<sub>5</sub> is synthesized by condensation of β-alanine and pantoic acid. β-alanine is produced by decarboxylation of L-aspartate, mediated by the enzyme aspartate α-decarboxylase (ADC) . Active ADC is formed when its inactive precursor, PanD, binds to a regulatory complex composed of acetyl coenzyme A (AcCoA) and a protein known as PanZ. Formation of the PanD-PanZ-AcCoA complex causes the activation loop of PanD to fold into a β-pleated sheet, resulting in PanD autocleavage. Researchers hypothesize that this conformational change allows the Thr57 residue to cleave the N-terminal end of PanD to form ADC.The limited information on the role of PanZ in the synthesis of CoA has stimulated an investigation of its effect on ADC activity. Escherichia coli cells were provided with varying concentrations of PanZ, and the rate of β-alanine production was measured in three different conditions (Figure 1) . Reaction vessels were maintained at pH 6 to ensure optimal decarboxylation activity. <strong>Figure 1</strong> Catalytic activity of ADC in E. coli with increasing concentrations of L-aspartate Adapted from Monteiro DC, Patel V, Bartlett CP, et al. The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A. Chem Biol. 2015;22(4) :492-503. -In E. coli, high levels of CoA lead to decreased β-alanine synthesis. This is an example of: A) the competitive inhibition of ADC by PanZ-AcCoA. B) a positive feedback loop in which CoA stimulates its own synthesis. C) a negative feedback mechanism driven by AcCoA involving PanZ. D) the allosteric regulation of PanD by PanZ-AcCoA.

Figure 1 Catalytic activity of ADC in E. coli with increasing concentrations of L-aspartate
Adapted from Monteiro DC, Patel V, Bartlett CP, et al. The structure of the PanD/PanZ protein complex reveals negative feedback regulation of pantothenate biosynthesis by coenzyme A. Chem Biol. 2015;22(4) :492-503.
-In E. coli, high levels of CoA lead to decreased β-alanine synthesis. This is an example of:

Quizplus · Accepted Answer

11ecba2d_0e25_de9b_a3bf_e53266f57435_MD0008_00 Biosynthetic pathways can be regulated by negative or positive feedback loops. Positive feedback increases the amount of product synthesized by a pathway when a product activates enzymes and stimulates production of precursor molecules. Negative feedback, which is more common, inactivates enzymes and reduces the production of necessary precursor molecules. Product inhibition is a type of negative feedback mechanism in which the end product of a reaction pathway decreases its own production by binding to an enzyme or regulatory protein needed in an earlier step. Based on the passage, β-alanine is a precursor molecule in the production of CoA. Therefore, CoA is an end product that depends on β-alanine synthesis. The question states that E. coli bacteria with high levels of CoA display reduced rates of β-alanine synthesis, suggesting that accumulated CoA inhibits its own synthesis by reducing the concentration of its precursor, β-alanine. Figure 1 supports this negative feedback mechanism, showing that the CoA derivative AcCoA bound to PanZ decreases the production of β-alanine by inactivating the enzyme ADC. (Choice A) Competitive inhibitors increase the K_m value of an enzyme-substrate reaction but have no effect on V_max. Figure 1 shows that increasing the concentration of PanZ-AcCoA significantly decreases the V_max of the reaction, so PanZ-AcCoA is not a competitive inhibitor. (Choice B) In a positive feedback loop, the accumulated CoA would increase, not decrease, the rate of β-alanine synthesis. (Choice D) Based on the passage, allosteric regulation of PanD by Panz-AcCoA increases ADC activity by inducing PanD autocleavage, resulting in increased β-alanine synthesis. Educational objective: Positive feedback increases the amount of product synthesized by a pathway by activating enzymes and stimulating the production of precursor molecules. Negative feedback decreases the synthesis of products in a pathway by inactivating enzymes and reducing the production of necessary precursor molecules.