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Review
. 2020 May;31(5):898-906.
doi: 10.1681/ASN.2019101015. Epub 2020 Apr 6.

Fructose Production and Metabolism in the Kidney

Takahiko Nakagawa  1   2 , Richard J Johnson  3 , Ana Andres-Hernando  3 , Carlos Roncal-Jimenez  3 , Laura G Sanchez-Lozada  4 , Dean R Tolan  5 , Miguel A Lanaspa  3
Affiliations
Review

Fructose Production and Metabolism in the Kidney

Takahiko Nakagawa et al. J Am Soc Nephrol. 2020 May.

Abstract

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.

Keywords: fructolysis; fructoneogenesis; fructose; gluconeogenesis; glycolysis.

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Figures

Figure 1.
Figure 1.
The S1 and S2 of the proximal tubular cells cooporately metabolize fructose. Both proximal convoluted tubules (PCT) and proximal straight tubules (PST) participate in fructose (Fru) metabolism. AldoB, aldolase B; DHAP, dihydroxyacetate phosphate; FBPase, fructose 1,6-bisphosphatase; FK, fructokinase; Fru1P, fructose 1-phosphate; Fru1,6P2, fructose 1,6 bisphosphate; Glc, glucose; Glc6P, glucose 6-phosphate; G3P; glyeraldehyde 3-phosphate; G6Pase, glucose 6-phosphatase; Glut2/5, glucose transporter 2/5.
Figure 2.
Figure 2.
Both fructolysis and fructogenesis occuring in the kidney are modulated by uric acid. AR, aldose reductase; FA, fatty acid; FK, fructokinase; Fru, fructose; Fru6P, fructose 6-phosphate; Fru1,6P2, fructose 1,6 bisphosphate; DHAP, dihydroxyacetate phosphate; Glc, glucose; Glc6P, glucose 6-phosphate; G3P; glyeraldehyde 3-phosphate; OXPHOS, mitochondrial oxidative phosphorylation; PEP, phosphoenolpyruvate; PPP, pentose phosphate pathway; SDH, sorbitol dehydrogenase; TCA, tricarboxylic acid cycle.
Figure 3.
Figure 3.
Both dietary and endogenously produced fructose cause CKD, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. FK, fructokinase; NO, nitric oxide.
See this image and copyright information in PMC

References

    1. Johnson RJ, Stenvinkel P, Andrews P, Sanchez-Lozada LG, Nakagawa T, Gaucher E, et al.: Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts. J Intern Med 287: 252–262, 2020 - PMC - PubMed
    1. Junk WJ: Temporary fat storage, an adaptation of some fish species to the water level fluctuations and related environmental changes of the Amazon river. Amazoniana 9: 315–351, 1985
    1. Bairlein F: How to get fat: Nutritional mechanisms of seasonal fat accumulation in migratory songbirds. Naturwissenschaften 89: 1–10, 2002 - PubMed
    1. Stenvinkel P, Jani AH, Johnson RJ: Hibernating bears (Ursidae): Metabolic magicians of definite interest for the nephrologist. Kidney Int 83: 207–212, 2013 - PubMed
    1. Carey HV, Andrews MT, Martin SL: Mammalian hibernation: Cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83: 1153–1181, 2003 - PubMed

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