isuues Introduction to Kidney Metabolism Major metabolic pathways utilized by the kidney Reactive Oxygen Species (ROS) and Antioxidant Defense Metabolic Adaptations in Disease Summary
overview The kidney's unique metabolic needs support its complex roles in filtration, reabsorption, secretion, and regulation . Functions of the Kidney Electrolyte and pH balance Blood pressure regulation Waste excretion Metabolic processes like gluconeogenesis and ammonia production
Energy Metabolism in Kidney Regions Kidney Regions and Energy Needs Cortex : Rich in mitochondria Primarily relies on oxidative phosphorylation Uses aerobic metabolism due to high oxygen perfusion Medulla : Lower oxygen availability, uses glycolysis (anaerobic metabolism) Helps prevent hypoxia in this area
Major metabolic pathways utilized by the kidney Glucose Metabolism in the Kidney Amino Acid and Ammonia Metabolism Lipid Metabolism in the Kidney Fructose metabolism in kidney
Glucose Metabolism in the Kidney Proximal Tubule : Prefers glutamine and fatty acids over glucose for energy Active site for gluconeogenesis, especially during fasting Glucose Reabsorption Sodium-glucose cotransporters (SGLTs) reabsorb nearly all filtered glucose Critical for blood glucose homeostasis
Amino Acid and Ammonia Metabolism Role of Glutamine : Glutamine is converted to ammonia and alpha- ketoglutarate . Ammonia acts as a buffer in urine to maintain acid-base balance Increases during metabolic acidosis Gluconeogenesis : Kidney is second only to the liver in gluconeogenesis during fasting/starvation
Lipid Metabolism in the Kidney Fatty Acid Oxidation : Proximal tubule cells prefer fatty acids for energy Rich in mitochondria, enabling high levels of beta-oxidation Impairment in fatty acid oxidation is linked to kidney diseases (e.g., diabetic nephropathy) Significance : Fatty acid oxidation is essential for maintaining tubular health and function.
Fructose metabolism in kidney Primary Site: Proximal Straight Tubule Transporter : GLUT5 (Glucose Transporter 5) on the apical side of the cell membrane Function : Absorbs urinary fructose, which is metabolized by fructokinase in the cytosol Additional Site: Proximal Convoluted Tubule Enzymes Present : Fructokinase and Aldolase B Clinical Note : In hereditary fructose intolerance , lack of aldolase B causes toxic accumulation of fructose 1-phosphate in the proximal convoluted tubule
Reactive Oxygen Species (ROS) and Antioxidant Defense ROS Production High metabolic activity leads to significant ROS production, especially in the proximal tubules ROS primarily generated during fatty acid and amino acid metabolism Antioxidant Mechanisms The kidney has antioxidant systems (e.g., superoxide dismutase, catalase) to prevent oxidative damage
Metabolic Adaptations in Disease Chronic Kidney Disease ( CKD) :Mitochondrial function is often compromised, leading to a shift towards glycolysis Metabolic shifts can contribute to fibrosis and progressive functional decline Diabetes Hyperglycemia stresses glucose reabsorption capacity, increasing ROS production Chronic stress accelerates progression to diabetic nephropathy
Summary Key Takeaways Kidney metabolism is region-specific, with distinct processes in the cortex and medulla Glucose, amino acid, and lipid metabolism are adapted to meet renal functions Metabolic shifts in disease conditions (e.g., CKD, diabetes) can lead to pathology