Metabolic requirements of the nephron

Abstract

The mammalian kidney is a complex organ that has several metabolically active cell types to aid in waste filtration, salt-water balance, and electrolyte homeostasis in the body. These functions are done primarily through the nephron, which relies on strict regulation of various metabolic pathways. Any deviations in the metabolic profile of nephrons or their precursor cells called nephron progenitors can lead to renal pathologies and abnormal development. Metabolism encompasses the mechanisms by which cells generate intermediate molecules and energy in the form of adenosine triphosphate (ATP). ATP is required by all cells and is mainly generated through glycolysis, fatty acid oxidation, and oxidative phosphorylation. During kidney development, self-renewing or proliferating cells rely on glycolysis to a greater extent than the other metabolic pathways to supply energy, replenish reducing equivalents, and generate nucleotides. However, terminally differentiated cell types rely more heavily on fatty acid oxidation and oxidative phosphorylation performed in the mitochondria to fulfill energy requirements. Further, the mature nephron is comprised of distinct segments and each segment utilizes metabolic pathways to varying degrees depending on the specific function. This review will focus on major metabolic processes performed by the nephron during health and disease.

Keywords: Fatty acid oxidation; Glycolysis; Kidney; Metabolism; Nephron; Oxidative phosphorylation.