70. Pharmacology - Metabolic Energetics & Drug Metabolism in the Kidneys

The study of energy use by the kidneys for normal functioning.

How the kidneys process and eliminate drugs from the body.

The delivery of nutrients to different parts of the kidneys for energy.

The rate of oxygen use by the kidneys' cells.

The maintenance of the right balance of oxidation and reduction in the kidneys.

The creation of new mitochondria, the powerhouses of the cells.

How the changes in mitochondrial function affect the kidneys during aging.

The kidneys have a high oxygen demand, second only to the heart, despite extracting relatively little oxygen from the blood.

Kidneys are vulnerable to low oxygen levels (hypoxia), which can lead to both acute and chronic kidney diseases.

Most of the kidney's energy comes from oxidative metabolism (using oxygen) within mitochondria.

The sodium pump (Na+/K+-ATPase) in kidney cells uses ATP to move sodium out and potassium in, essential for kidney function.

The rate of ATP production by mitochondria is tightly linked to the rate of ATP consumption by the Na+ pump, showing a close relationship between energy supply and demand.

The kidneys can produce glucose from non-carbohydrate sources (like amino acids) to maintain blood sugar levels.

Understanding how drugs are processed in the kidneys is crucial to understand normal kidney function and how drug dosage impacts it.

The kidneys are a major site of drug elimination, especially for charged molecules (anions and cations).

Different drugs can compete for the same renal transporters, potentially affecting their effectiveness or causing toxicity.

Competition between drugs and naturally occurring substances (e.g., uric acid) can lead to kidney damage (acute kidney injury - AKI).

The outer layer of the kidney (cortex) prefers to use fats, ketone bodies, and lactate as fuel, not glucose.

Inner parts of the kidney (medulla) rely on different fuel sources compared to the cortex, using fats, ketone bodies, and lactate.

The kidneys run both glucose breakdown (glycolysis) and synthesis (gluconeogenesis) simultaneously.

The proximal convoluted tubule (PCT) doesn't process much glucose, unlike other parts of the kidney.

The thick ascending limb of Henle's loop (TALH) and distal convoluted tubule (DCT) efficiently break down glucose.

The collecting tubules excel at using glucose and generating lactate while also performing traditional energy production.

The kidney's production of glucose (gluconeogenesis) is essential to recover carbon compounds lost during ammonia formation.

The complex network of glucose metabolism pathways in the kidneys likely evolved to handle fluctuating glucose demands and electrolyte loads.

A protein that activates mitochondrial biogenesis by moving to the nucleus and turning on genes for mitochondrial components.

A protein crucial for mitochondrial DNA replication and transcription, essential for mitochondrial function and biogenesis.

A process that uses electrons from food to make ATP, the cell's energy currency, within mitochondria.

A series of chemical reactions that break down food molecules to generate energy-rich molecules used in Oxphos.

Receptors on cell surfaces that activate intracellular signaling pathways, including those involved in mitochondrial biogenesis.

A protein kinase activated by GPCRs that phosphorylates and activates other proteins, including PGC-1a.

An enzyme that produces nitric oxide (NO), a signaling molecule that activates the production of cGMP, which in turn promotes mitochondrial biogenesis.

A signaling molecule that activates PGC-1a, promoting mitochondrial biogenesis.

Nuclear receptors that can be activated by drugs or other molecules to promote mitochondrial biogenesis.

A protein activated by high NAD+:NADH ratios that promotes mitochondrial biogenesis by activating PGC-1a.

SIRT1, a protein in the nucleus, regulates gene expression, protects against cellular stress, and plays a role in metabolism.

SIRT1 can limit inflammation by reducing the activity of NF-κB, a factor that activates pro-inflammatory genes.

SIRT1 deactivates p53 and FoxO proteins, reducing cell death and aging after DNA damage and oxidative stress.

SIRT3, a mitochondrial sirtuin, regulates the acetylation of proteins within mitochondria, boosting energy production and protecting against stress.

SIRT4, another mitochondrial sirtuin, has opposite effects to SIRT3. It inactivates enzymes involved in energy and detoxification, but promotes fat storage.