Protein acetylation effects on enzyme activity and metabolic pathway fluxes

Author(s):  
Álvaro Marín‐Hernández ◽  
José S. Rodríguez‐Zavala ◽  
Ricardo Jasso‐Chávez ◽  
Emma Saavedra ◽  
Rafael Moreno‐Sánchez

2021 ◽  
Author(s):  
Jie Pei ◽  
Yueming Yuan ◽  
Dayong Tian ◽  
Fei Huang ◽  
Chengguang Zhang ◽  
...  

Rabies, caused by rabies virus (RABV), is a widespread zoonosis that is nearly 100% fatal. Alteration of the metabolic environment affects viral replication and the immune response during viral infection. In this study, glucose uptake was increased in mouse brains at the late stage of infection with different RABV strains (lab-attenuated CVS strain and wild-type DRV strain). To illustrate the mechanism underlying glucose metabolism alteration, comprehensive analysis of lysine acetylation and target analysis of energy metabolites in mouse brains infected with CVS and DRV strains were performed. A total of 156 acetylated sites and 115 acetylated proteins were identified as significantly different during RABV infection. Compared to CVS- and mock-infected mice, the lysine acetylation levels of glycolysis and tricarboxylic acid (TCA) cycle enzymes were decreased, and enzyme activity was upregulated in DRV-infected mouse brains. Metabolomic analysis revealed that high levels of oxaloacetate (OAA) in RABV-infected mouse brains. Specifically, the OAA level in CVS-infected mouse brains was higher than that in DRV-infected mouse brains, which contributed to the enhancement of the metabolic rate at the substrate level. Finally, we confirmed that OAA could reduce excessive neuroinflammation in CVS-infected mouse brains by inhibiting JNK and P38 phosphorylation. Taken together, this study provides fresh insight into the different strategies the host adapts to regulate glucose metabolism for energy requirements after different RABV strain infection and suggest that OAA treatment could be a potential strategy to prevent neural damage during RABV infection. IMPORTANCE Both viral replication and the host immune response are highly energy-dependent. It is important to understand how the rabies virus affects energy metabolism in the brain. Glucose is the direct energy source for cell metabolism. Previous studies have revealed that there is some association between acetylation and metabolic processes. In this study, comprehensive protein acetylation and glucose metabolism analysis were conducted to compare glucose metabolism in mouse brains infected with different RABV strains. Our study demonstrates that the regulation of enzyme activity by acetylation and OAA accumulation at the substrate level are two strategies for the host to respond to the energy requirements after RABV infection. Our study also indicates the potential role OAA could play in neuronal protection by suppressing excessive neuroinflammation.





RSC Advances ◽  
2017 ◽  
Vol 7 (45) ◽  
pp. 28527-28534 ◽  
Author(s):  
Jian-Zhong Xu ◽  
Wei-Liu Yan ◽  
Wei-Guo Zhang

Six key enzymes are vital for MK-7 production, but the same enzyme has different effect on MK-7 production in different cultivating methods. Thus, the high enzyme activity and high-traffic biosynthetic pathway are beneficial to synthesize MK-7.



1996 ◽  
Vol 314 (3) ◽  
pp. 753-760 ◽  
Author(s):  
Boris N. KHOLODENKO ◽  
Guy C. BROWN

It is widely assumed that within a metabolic pathway inhibition of an enzyme causes the control exerted by that enzyme over the flux through its own reaction to increase, whereas activation causes its control to decrease. This assumption forms the basis of a number of experimental methods. For a pathway conceptually divided into two enzyme groups connected via a single metabolite we have derived a general condition under which this assumption is false, and thus the pathway shows paradoxical control behaviour, i.e. increased control with activation and decreased control with inhibition of an enzyme or group of enzymes. Paradoxical control behaviour occurs widely when enzyme activity is altered by changing Km (if an enzyme is already close to saturation by its substrate), but may also occur with changes in Vmax. when the elasticity to the linking metabolite increases with its concentration (as in some cases of sigmoidal and exponential kinetics or for reactions catalysed by isoenzymes). These findings suggest that enzymes with sigmoidal kinetics may have low control in the absence of activation, but may gain control with activation, and thus have beneficial regulatory properties.



2014 ◽  
Vol 912-914 ◽  
pp. 1919-1923 ◽  
Author(s):  
Teng Yue Wang ◽  
Xi Hong Li ◽  
Lan Chen ◽  
Xia Liu

According to the observation to chilling injury symptoms of Lingwu Long Jujube, as well as the analysis to the enzyme activity related to the anti-adversity of plant in this paper, it is found that the disease will outbreak in 4-10 hours after low temperature pre-cooling, and the main symptoms include sinking semi-spherical dry spots and fibrosis of flesh. It is measured that the activity of polyphenol oxidase and phenylalnine ammonialyase in the diseased fruit is 0.34U and 101.689U separately, but the activity is 0.133U and 49.156U separately in healthy fruits, and there is a significant difference, but the difference of peroxidase is not significant. It laid the foundation for further research on relationship between chilling injury and metabolic pathway.



Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.







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