An Assessment of the Chemiosmotic Hypothesis of Mitochondrial Energy Transduction

Author(s):  
W.W. Wainio
2019 ◽  
Vol 3 (5) ◽  
pp. 573-578 ◽  
Author(s):  
Kwanwoo Shin

Living cells naturally maintain a variety of metabolic reactions via energy conversion mechanisms that are coupled to proton transfer across cell membranes, thereby producing energy-rich compounds. Until now, researchers have been unable to maintain continuous biochemical reactions in artificially engineered cells, mainly due to the lack of mechanisms that generate energy-rich resources, such as adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). If these metabolic activities in artificial cells are to be sustained, reliable energy transduction strategies must be realized. In this perspective, this article discusses the development of an artificially engineered cell containing a sustainable energy conversion process.


Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 31
Author(s):  
Samuel E. Weinberg ◽  
Le Yu Sun ◽  
Allison L. Yang ◽  
Jie Liao ◽  
Guang Yu Yang

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.


2019 ◽  
Vol 295 (6) ◽  
pp. 1551-1564 ◽  
Author(s):  
Kelly E. Du Pont ◽  
Russell B. Davidson ◽  
Martin McCullagh ◽  
Brian J. Geiss

The unwinding of dsRNA intermediates is critical for the replication of flavivirus RNA genomes. This activity is provided by the C-terminal helicase domain of viral nonstructural protein 3 (NS3). As a member of the superfamily 2 (SF2) helicases, NS3 requires the binding and hydrolysis of ATP/NTP to translocate along and unwind double-stranded nucleic acids. However, the mechanism of energy transduction between the ATP- and RNA-binding pockets is not well-understood. Previous molecular dynamics simulations conducted by our group have identified Motif V as a potential “communication hub” for this energy transduction pathway. To investigate the role of Motif V in this process, here we combined molecular dynamics, biochemistry, and virology approaches. We tested Motif V mutations in both the replicon and recombinant protein systems to investigate viral genome replication, RNA-binding affinity, ATP hydrolysis activity, and helicase-mediated unwinding activity. We found that the T407A and S411A substitutions in NS3 reduce viral replication and increase the helicase-unwinding turnover rates by 1.7- and 3.5-fold, respectively, suggesting that flaviviruses may use suboptimal NS3 helicase activity for optimal genome replication. Additionally, we used simulations of each mutant to probe structural changes within NS3 caused by each mutation. These simulations indicate that Motif V controls communication between the ATP-binding pocket and the helical gate. These results help define the linkage between ATP hydrolysis and helicase activities within NS3 and provide insight into the biophysical mechanisms for ATPase-driven NS3 helicase function.


2002 ◽  
Vol 362 (1-2) ◽  
pp. 51-55 ◽  
Author(s):  
Zhiwei Wang ◽  
Zhonghuai Hou ◽  
Houwen Xin

1984 ◽  
Vol 56 (2) ◽  
pp. 520-525 ◽  
Author(s):  
G. A. Brooks ◽  
C. M. Donovan ◽  
T. P. White

o assess the effects of gradient and running speed on efficiency of exercise, and to evaluate contributions of oxidative and anaerobic energy production (Ean) during locomotion, two sets of experiments were performed. The caloric expenditures of rats were determined from O2 consumption (VO2) while they ran at three speeds (13.4, 26.8, and 43.1 m/min) on five grades (1, 5, 10, 15, and 20%). In addition, lactate turnover (LaT) and oxidation (Laox) were determined on rats at rest or during running at 13.4 and 26.8 m/min on 1% grade, respectively. Lactate production not represented in the VO2 (i.e., Ean) was calculated from the LaT not accounted for by oxidation [(LaT an) = LaT-Laox)]. The Ean was calculated as: Ean = [LaT an(mumol/min)] [1.38 ATP/La] [11 mcal/mumol ATP]. Gross efficiency of exercise (the caloric equivalent of external work/caloric equivalent of VO2 X 100) ranged from 1.7 to 4.5%. Apparent efficiency (the inverse of the regression of caloric equivalent of VO2 on the caloric equivalent of work X 100) ranged from 20.5 to 26.4% and reflected the metabolic response of rats to applied external work. The contribution of Ean to total energy turnover ranged from 1.6% at rest to 0.8% during running at 13.4 m/min on a 1% grade. Despite active LaT during steady-state exercise, Ean contributes insignificantly to total energy transduction, because over 70% of the lactate produced is removed through oxidation. VO2 adequately represents metabolism under these conditions.


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