scholarly journals The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1068 ◽  
Author(s):  
Joséphine Zangari ◽  
Francesco Petrelli ◽  
Benoît Maillot ◽  
Jean-Claude Martinou

Pyruvate, the end product of glycolysis, plays a major role in cell metabolism. Produced in the cytosol, it is oxidized in the mitochondria where it fuels the citric acid cycle and boosts oxidative phosphorylation. Its sole entry point into mitochondria is through the recently identified mitochondrial pyruvate carrier (MPC). In this review, we report the latest findings on the physiology of the MPC and we discuss how a dysfunctional MPC can lead to diverse pathologies, including neurodegenerative diseases, metabolic disorders, and cancer.

1995 ◽  
Vol 269 (1) ◽  
pp. E61-E66
Author(s):  
J. M. Egan ◽  
T. E. Henderson ◽  
M. Bernier

The present study was undertaken to define the role of L-arginine (L-Arg) in glucose metabolism in differentiated 3T3-L1 adipocytes in culture. L-Arg alone had no effect on 2-deoxyglucose uptake or basal glycogen synthesis, but this amino acid increased by 153 +/- 10% (P < 0.01) the incorporation of glucose into glycogen in insulin-treated cells. L-Glutamate (L-Glu), a major metabolite of L-Arg, also enhanced insulin-stimulated glycogen synthesis. The response to insulin was not altered by L-lysine (L-Lys), but the effect of L-Arg was markedly attenuated by L-Lys. Cell incubation with L-Arg markedly enhanced arginase-mediated urea synthesis, whereas L-Lys abolished this response. The stimulatory effect of L-Arg on insulin-stimulated glycogen synthesis did not appear to be accounted for by the generation of polyamines or the production of nitric oxide, both potentially derived from the enzymatic conversion of L-Arg. In the presence of insulin, cellular ATP levels were significantly increased by L-Arg, L-Glu, and L-Lys as well. These data suggest that metabolic degradation of L-Arg not related to citric acid cycle activity is important in the mechanism by which L-Arg enhances insulin-stimulated glycogen synthesis.


Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1410 ◽  
Author(s):  
Gerresheim ◽  
Roeb ◽  
Michel ◽  
Niepmann

Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the “Warburg Effect” and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.


2002 ◽  
Vol 277 (34) ◽  
pp. 30409-30412 ◽  
Author(s):  
Oliver E. Owen ◽  
Satish C. Kalhan ◽  
Richard W. Hanson

Author(s):  
Lina Wang ◽  
Donghai Cui ◽  
Xueyuan Zhao ◽  
Miao He

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