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In 1971, Dr. Akira Endo, working at the Sankyo company in Tokyo speculated that fungi not only contained antibiotics but also inhibitors of other processes such as cholesterol metabolism. Over a period of several years, he screened more than 6,000 fungal cultures until a positive result emerged. This compound, which was named compactin, came from the blue-green mold Penicillium citrinum Pen-5 that was isolated from a rice sample collected at a grain shop in Kyoto. Based on biochemical assays, compactin is the first known statin. 1. The original kinetics data for compactin inhibition of HMG-CoA reductase enzyme that was published by Dr. Endo in 1976 is shown on the right. a) Determine the Km and Vmax values for enzymatic activity. Do NOT forget the units. Answers can be expressed either as a fraction or in decimals. With No inhibitor: Km = -60 Vmax= 1/V, (nanomoles/min)-1 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 -40 -20 0 + 24 nM compactin + 70 nM compactin None T T 20 40 60 1/[HMG-CoA], (mM)-1 With 24 nM compactin: Apparent Km= ; Apparent Vmax = b) What happens to the measured Vmax with increasing amounts of compactin? (select one) decreases increases does not change c) What happens to the measured Km with increasing amounts of compactin? (select one) decreases does not change increases

In 1971, Dr. Akira Endo, working at the Sankyo company in Tokyo speculated that fungi not only contained antibiotics but also inhibitors of other processes such as cholesterol metabolism. Over a period of several years, he screened more than 6,000 fungal cultures until a positive result emerged. This compound, which was named compactin, came from the blue-green mold Penicillium citrinum Pen-5 that was isolated from a rice sample collected at a grain shop in Kyoto. Based on biochemical assays, compactin is the first known statin. 1. The original kinetics data for compactin inhibition of HMG-CoA reductase enzyme that was published by Dr. Endo in 1976 is shown on the right. a) Determine the Km and Vmax values for enzymatic activity. Do NOT forget the units. Answers can be expressed either as a fraction or in decimals. With No inhibitor: Km = -60 Vmax= 1/V, (nanomoles/min)-1 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 -40 -20 0 + 24 nM compactin + 70 nM compactin None T T 20 40 60 1/[HMG-CoA], (mM)-1 With 24 nM compactin: Apparent Km= ; Apparent Vmax = b) What happens to the measured Vmax with increasing amounts of compactin? (select one) decreases increases does not change c) What happens to the measured Km with increasing amounts of compactin? (select one) decreases does not change increases

Biochemistry
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
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**Transcription for Educational Website** --- In 1971, Dr. Akira Endo, working at the Sankyo company in Tokyo, speculated that fungi not only contained antibiotics but also inhibitors of other processes such as cholesterol metabolism. Over a period of several years, he screened more than 6,000 fungal cultures until a positive result emerged. This compound, which was named compactin, came from the blue-green mold *Penicillium citrinum* Pen-5 that was isolated from a rice sample collected at a grain shop in Kyoto. Based on biochemical assays, compactin is the first known statin. 1. **The original kinetics data for compactin inhibition of HMG-CoA reductase enzyme that was published by Dr. Endo in 1976 is shown on the right.** a) Determine the K\(_m\) and V\(_{\text{max}}\) values for enzymatic activity. *Do NOT forget the units. Answers can be expressed either as a fraction or in decimals.* **With No inhibitor:** K\(_m\) = _______________________; V\(_{\text{max}}\) = _______________________ **With 24 nM compactin:** Apparent K\(_m\) = ___________________; Apparent V\(_{\text{max}}\) = _______________ b) What happens to the measured V\(_{\text{max}}\) with increasing amounts of compactin? *(select one)* - increases - decreases - does not change c) What happens to the measured K\(_m\) with increasing amounts of compactin? *(select one)* - increases - decreases - does not change d) Based on your answers above, what type of reversible inhibitor is compactin? ___________________ e) Based on your answers above, predict where compactin binds to HMG-CoA reductase. *(select one)* - Inside the active site - Outside the active site **Explanation of the Graph:** The graph on the right plots enzyme activity against varying concentrations of compactin. The y-axis represents the reciprocal of velocity, 1/V (nanomoles/min)\(^{-1}\), while the x-axis shows the reciprocal of the HMG-CoA concentration, 1/[HMG-CoA
Transcribed Image Text:**Transcription for Educational Website** --- In 1971, Dr. Akira Endo, working at the Sankyo company in Tokyo, speculated that fungi not only contained antibiotics but also inhibitors of other processes such as cholesterol metabolism. Over a period of several years, he screened more than 6,000 fungal cultures until a positive result emerged. This compound, which was named compactin, came from the blue-green mold *Penicillium citrinum* Pen-5 that was isolated from a rice sample collected at a grain shop in Kyoto. Based on biochemical assays, compactin is the first known statin. 1. **The original kinetics data for compactin inhibition of HMG-CoA reductase enzyme that was published by Dr. Endo in 1976 is shown on the right.** a) Determine the K\(_m\) and V\(_{\text{max}}\) values for enzymatic activity. *Do NOT forget the units. Answers can be expressed either as a fraction or in decimals.* **With No inhibitor:** K\(_m\) = _______________________; V\(_{\text{max}}\) = _______________________ **With 24 nM compactin:** Apparent K\(_m\) = ___________________; Apparent V\(_{\text{max}}\) = _______________ b) What happens to the measured V\(_{\text{max}}\) with increasing amounts of compactin? *(select one)* - increases - decreases - does not change c) What happens to the measured K\(_m\) with increasing amounts of compactin? *(select one)* - increases - decreases - does not change d) Based on your answers above, what type of reversible inhibitor is compactin? ___________________ e) Based on your answers above, predict where compactin binds to HMG-CoA reductase. *(select one)* - Inside the active site - Outside the active site **Explanation of the Graph:** The graph on the right plots enzyme activity against varying concentrations of compactin. The y-axis represents the reciprocal of velocity, 1/V (nanomoles/min)\(^{-1}\), while the x-axis shows the reciprocal of the HMG-CoA concentration, 1/[HMG-CoA
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