When both K_m and V_max are altered, Is the enzyme inhibited or activated?

Abstract

Enzyme activators lower Km (the Michaelis constant) and/or raise Vmax (the asymptotic reaction velocity at infinite substrate concentration); conversely, inhibitors raise Km and/or lower Vmax. But what if an effector moves both Km and Vmax in the same direction? Uncompetitive inhibitors, which decrease both Km and Vmax by the same factor, are the most common example of this. A less well‐known example occurs often when crowding agents are added to the buffer in order to mimic the environment commonly encountered in vivo. Crowding agents tested on different enzymes have been shown to have every conceivable effect on Km or Vmax, causing them to rise, fall, or stay the same. In this article, a mathematical analysis is presented allowing biochemists to judge whether an effector that causes Km and Vmax to both move in the same direction serves as an inhibitor, an activator, or most surprising, as both. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):446–449, 2019.

Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment

“…In the present meta-analysis, a significant reduction in the concentration of 5-HIAA and Trp was detected in hypoinsulinemic animals, as well as an alteration in TPH function, witnessed by a decrease in TPH activity and Vmax and an elevation in TPH K m [170], whereas a significant increase in Trp accumulation and 5-HIAA levels was found in the hyperinsulinemic model. These findings support the insulin role in the regulation of Trp brain availability [171] and thus, the presumptive downregulation of the Trp pathway, at least toward serotonin and 5-HIAA formation, under insulin deficiency conditions.…”

Cysteine oxidation as a regulatory mechanism of Arabidopsis plastidial NAD‐dependent malate dehydrogenase

“…At a constant NADH concentration of 0.2 mM, the reduced enzyme exhibited a K m (OAA) of 52 ± 4 μM and a V max (OAA) of 1099 ± 22.5 U mg −1 protein. In contrast, oxidizing conditions raised K m (OAA) to 94 ± 8 μM and lowered V max to 630.2 ± 15.6 U mg −1 protein (Figure 4b), a characteristic feature of inhibition (Silverstein, 2019). Upon reduction, plNAD‐MDH exhibited a K m (NADH) of 115 ± 9 μM and a V max (NADH) of 1288 ± 53.5 U mg −1 protein at a constant OAA concentration of 1 mM.…”

The evolution of small molecule enzyme activators

“…Activators that decrease K m are referred to as K-type and those that increased V max as V-type activators and therefore both of these parameters must be assessed to characterize activators. 9,22 Traditional methods for identifying inhibitors can also be employed for the identification of enzyme activators. Fluorescence resonance energy transfer (FRET) and other fluorescent based assay, activity-based protein profiling (ABPP) are some of the methods that have proved successful in the literature.…”