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

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Questions and Answers

What is the primary focus of metabolic energetics in relation to kidney function?

Facilitating filtration processes in glomeruli

Transporting nutrients across nephron cells

Regulating blood pressure

Sustaining kidney function through energy metabolism (correct)

How does nutritional status affect kidney function?

It influences substrate supply and respiratory rates. (correct)

It has no effect on kidney function.

It regulates hormone levels in the kidneys.

It only affects drug metabolism.

Which factor is NOT considered in the regulation of mitochondrial responses in kidney function?

Redox processes

Nutritional factors

Environmental factors

Pathogen exposure (correct)

What role do Sirtuins play in kidney function according to the lecture outline?

They regulate mitochondrial biogenesis. Signup and view all the answers

Which of the following best describes mitochondrial turnover?

It involves both fission and fusion processes. Signup and view all the answers

What is a potential therapeutic target for kidney injury and disease?

Mitochondrial biogenesis Signup and view all the answers

How does aging affect kidney function according to the outlined content?

It causes functional changes in the kidneys. Signup and view all the answers

What is the primary source of ATP production in the kidneys?

Oxidative metabolism Signup and view all the answers

Which kidney function is directly linked to ATP production rates?

Renal Na+ pump Signup and view all the answers

What is a key consequence of renal hypoxia?

Susceptibility to acute and chronic renal disease Signup and view all the answers

Which of the following is NOT a function associated with renal mitochondria?

Calcium storage Signup and view all the answers

How do the kidneys compare to the heart in terms of oxygen consumption?

The kidneys have the second highest oxygen consumption after the heart Signup and view all the answers

What metabolic role do the kidneys fulfill aside from excretion?

They function as a gluconeogenic tissue. Signup and view all the answers

What enzymes do proximal tubules of the kidneys utilize for drug metabolism?

CYP enzymes, FMOs, GSTs, UGTs, and SULTs Signup and view all the answers

What does the renal Na+ pump function as regarding cellular respiration?

A 'pacemaker' for cellular respiration Signup and view all the answers

Which statement accurately describes oxygen extraction by the kidneys?

Oxygen extraction in the kidneys is moderate relative to blood flow. Signup and view all the answers

What is one of the main functions of SIRT1 in the regulation of gene expression?

Inhibits TNFa-dependent transactivation of NF-kB. Signup and view all the answers

Which statement correctly describes the role of SIRT3 in mitochondria?

It regulates the activity of complex II and ATP synthase. Signup and view all the answers

How does SIRT4 primarily affect cellular metabolism?

It induces lipogenesis through malonyl CoA decarboxylase deacetylation. Signup and view all the answers

Which of the following is NOT a result of SIRT1 deacetylation activity following DNA damage?

Increased apoptosis. Signup and view all the answers

What enzyme does SIRT5 directly activate in relation to the urea cycle?

Carbamoyl phosphate synthetase 1. Signup and view all the answers

What is the primary metabolic fuel for respiration in the kidney cortex?

Endogenous lipids Signup and view all the answers

In which region of the nephron is glucose oxidation particularly high?

Thick ascending limb of Henle’s loop Signup and view all the answers

Which metabolic pathway is linked closely to free-water clearance in the kidney?

Glycolysis Signup and view all the answers

What is the role of gluconeogenesis in the kidneys?

To recover carbon compounds generated during renal ammoniagenesis Signup and view all the answers

Which nephron segments have no gluconeogenic enzymes present?

Distal nephron segments Signup and view all the answers

What potential risk is associated with competition between drugs and endogenous metabolites in renal transporters?

Increased risk of acute kidney injury Signup and view all the answers

Which pathway does the proximal convoluted tubule primarily utilize?

Gluconeogenic pathway Signup and view all the answers

Which statement accurately reflects the fuel preference in the outer medulla of the kidney?

Functions mainly on ketone bodies Signup and view all the answers

Which statement about metabolic heterogeneity in the nephron is true?

Different nephron segments may utilize different metabolic pathways Signup and view all the answers

What is a key function of glucose metabolism in the kidneys?

Reabsorption of sodium and potassium Signup and view all the answers

What is the role of PGC-1a in the process of mitochondrial biogenesis?

It translocates to the nucleus to activate gene transcription related to mitochondrial function. Signup and view all the answers

How does activation of GPCRs lead to the stimulation of PGC-1a?

By enhancing eNOS activity which increases cGMP levels. Signup and view all the answers

What is the function of cGMP in the context of mitochondrial biogenesis?

It serves as a secondary messenger activating PGC-1a. Signup and view all the answers

Which of the following factors could lead to the activation of PGC-1a?

Caloric restriction increasing eNOS activity. Signup and view all the answers

Which transcription factors directly interact with PGC-1a to induce mitochondrial biogenesis?

Nuclear respiratory factor 1 and 2. Signup and view all the answers

What metabolic ratios are associated with the activation of SIRT1 and its effect on PGC-1a?

High NAD+:NADH ratios. Signup and view all the answers

What two complexes comprise the Mammalian Target of Rapamycin (mTOR)?

mTORC1 and mTORC2. Signup and view all the answers

How are estrogen-related receptors (ERRs) relevant to mitochondrial biogenesis?

They can activate nuclear receptors to promote mitochondrial biogenesis. Signup and view all the answers

What type of chemical signaling is associated with the activation of mTOR complexes?

G-protein coupled signaling. Signup and view all the answers

Which outcome results from high AMP:ATP ratios in the context of mitochondrial function?

Activation of AMPK, leading to PGC-1a activation. Signup and view all the answers

Study Notes

Metabolic Energetics and Drug Metabolism in the Kidneys

Kidneys are critical for maintaining energy and normal function; second only to the heart in oxygen consumption.
95% of kidney ATP is from oxidative metabolism, making renal mitochondria crucial.
Nutritional status impacts kidney function through substrate supply and respiratory rates.
Redox processes in mitochondria respond to nutritional and environmental factors, offering therapeutic targets for kidney injury and disease.
Mitochondrial biogenesis' role in kidney function and response to environmental changes, offering potential therapeutic targets.
Kidney function changes with aging related to mitochondrial responses.
Drug metabolism in the kidneys is important for understanding normal kidney function, particularly for anionic and cationic drugs.
Kidney drug metabolism (proximal tubules) shares similar activities with the liver.
Species differences in renal drug metabolism, emphasizing careful extrapolation of data.
Drug transport across the kidney membrane is vital.
Proximal tubules are main site of organic anion/cation transport.
Specialized transporter families exist in proximal tubules.
Energy source heterogeneity found within different kidney regions.
Glucose is a less preferred fuel for respiration in the cortex compared to fatty acids, etc.
Glucose metabolism pathways differs across nephron segments.
Proximal convoluted tubules do not metabolize glucose.
Thick ascending limb and distal convoluted tubule has high capacity for glucose (and lactate) oxidation.
Gluconeogenesis and oxidative pathways are active in collecting tubules.
Heterogeneity in mitochondrial volume density across the nephron segments.
Mitochondrial density in the nephron is different across segments.
Mitochondrial cristae membrane surface and O2 consumption aid in estimating ATP formation rates.
Drug metabolism enzymes crucial in kidneys, in addition to drug metabolism in the cells.
Proximal tubules have the highest drug metabolism activity.
Specialized localization of drug enzymes in various nephron segments.
Important role of drug metabolism in fluid balance and blood pressure regulation.
Cytoplasmic and mitochondrial gluconeogenic enzymes concentrated in PCT and PST.
Na, K-ATPase activity varies significantly in nephron segments.
Mitochondrial function in kidney is both a target and a source for ROS.
Oxidative stress and antioxidant defense system in renal mitochondria.
ROS in the kidneys causes mtDNA damage, lipid/protein damage, and inhibits mitochondrial functions.
Mitochondrial turnover (fission and fusion) and biogenesis are regulated processes.
mTOR and AMPK regulate mitochondrial processes by nutrient sensing.
Mitochondrial fission isolates damaged mitochondria for mitophagy.
Mitochondrial fusion creates oxidative phosphorylation through elongation.
Mitophagy is a process by which mitochondria are degraded and removed.
Mitochondrial biogenesis increases ATP production, responding to higher energy demands.
Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) in the cytoplasm, activated by transcription factors, is important for mitochondrial biogenesis.
mTORC1 and AMPK influence catabolic/anabolic processes and nutrient sensing within renal cells.
Sirtuins are NAD+-dependent deacetylases, involved in transcriptional regulation, gene expression, and cellular energy homeostasis.
SIRT1, 2, 3, 5, 6, and 7 regulate mitochondrial function and are regulated by NAD+.
SIRT3 in mitochondria plays a major role in antioxidant pathways.
SIRT7 protects cells from injury.
SIRT5 in the urea cycle and energy regulation.
Aging's impact on kidney morphology, function and compensation.
Loss of nephrons, increased cellular senescence, interstitial fibrosis, tubular atrophy, and glomerulosclerosis are associated with aging.
Regenerative failure is associated with age-related changes in kidneys.
Microvascular rarefaction influenced by pro-/antiangiogenic factors.
Cellular senescence and SASP are major factors.
Cellular autophagy is important for age-related response in kidney.
Autophagy is increasingly reduced in the aged kidney, leading to reduced degradation of intracellular material.

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Description

This quiz explores the critical role of kidneys in metabolic energetics and drug metabolism. Learn about mitochondrial function, oxidative metabolism, and how nutritional status influences kidney performance. Additionally, the quiz highlights the implications of aging and species differences in renal drug metabolism.