p.1
Remote Interorgan Communication
What is the role of SLC and ABC transporters in remote interorgan communication?
They mediate communication via small molecules of high informational content, such as metabolites and signaling molecules.
p.1
Remote Interorgan Communication
How do intestinal transporters compensate for renal dysfunction in CKD?
Intestinal ABCG2 transporters take over from renal SLC uric acid transporters as tubular function declines.
p.1
Remote Interorgan Communication
What is the Remote Sensing and Signaling Hypothesis?
It posits that multispecific drug transporters regulate remote interorgan and interorganismal communication via metabolites and signaling molecules.
p.1
Uremic Syndrome and Metabolite Regulation
What factors are thought to induce the expression of intestinal transporters in renal disease?
High urate levels and certain uremic toxins accumulating due to renal disease.
p.7
Transport Mechanisms in the Kidney
What is the alternating access mode in transporter proteins?
It is a mechanism where the substrate and cosubstrates bind on one side of the membrane and the transporter transitions to release them on the other side.
p.4
Renal Amino Acid Transporters
What are the substrate affinities of B0AT1?
Substrate affinities range from 1–12 mM, with a preference for branched-chain amino acids and methionine.
p.5
SLC and ABC Transporters
What is the function of the transporter rBAT/b0,+AT?
It transports cationic amino acids and cystine in the proximal tubule.
p.5
Uremic Syndrome and Metabolite Regulation
What happens to glutamine during chronic metabolic acidosis?
It is upregulated and imported for deamination, contributing to gluconeogenesis.
p.7
Transport Mechanisms in the Kidney
How do antiporters differ from symporters and uniporters in terms of substrate binding?
Antiporters require a substrate-bound state to return to the initial conformation, while symporters and uniporters can transition back through a substrate-free occluded state.
p.7
Transport Mechanisms in the Kidney
What is the significance of the basolateral membrane in amino acid transport?
It may prevent efflux and serve as pathways for glutamate transport.
p.4
Transport Mechanisms in the Kidney
Why are proline and glycine inefficiently transported by broader amino acid transporters?
Proline has a secondary amino group and restricted flexibility, while glycine lacks a side chain.
p.5
SLC and ABC Transporters
What does LAT4 (SLC43A2) transport?
It allows efflux of branched-chain amino acids (BCAA), methionine, and phenylalanine.
p.5
SLC and ABC Transporters
What does the transporter PAT2 (SLC36A2) specifically transport?
It is the specific transporter for small neutral amino acids, particularly alanine, glycine, and proline.
p.1
Drug-Metabolite Interactions
Why is the Remote Sensing and Signaling Hypothesis clinically relevant?
It helps understand how drug-metabolite interactions can create the impression of renal dysfunction.
p.3
Renal Amino Acid Transporters
What type of amino acids does the LAT2 transporter handle?
It is involved in the transport of neutral amino acids.
p.6
Genetic Disorders Related to Amino Acid Transport
What is the genetic cause of Lysinuric Protein Intolerance (LPI)?
Mutations in the SLC7A7 transporter.
p.6
Genetic Disorders Related to Amino Acid Transport
What condition is caused by mutations in EAAT3?
Dicarboxylic aminoaciduria.
p.8
Transport Mechanisms in the Kidney
What is the mechanism of transport in Na+-driven glutamate transporters?
It involves an elevator-like movement of the transport domain.
p.2
Molecular Biology of Renal Amino Acid Transporters
What has molecular cloning and human genetics contributed to our understanding of?
Identification of almost all amino acid transporters in the apical and basolateral membrane.
p.6
Uremic Syndrome and Metabolite Regulation
What is the clinical relevance of cystinuria?
It causes the formation of kidney stones due to low solubility of cystine.
p.8
Transport Mechanisms in the Kidney
What is the significance of the hydrogen bond network in transporters?
It allows the helix to bend and interact with substrates and cotransported ions.
p.6
Pathophysiology of Chronic Kidney Disease (CKD)
What are the clinical symptoms of LPI?
Symptoms vary widely and can be very severe.
p.8
Renal Amino Acid Transporters
What additional function does the 4F2 heavy chain have?
It is involved in integrin signaling.
p.8
Transport Mechanisms in the Kidney
What is the structural feature of glutamate transporters?
They form trimers that stabilize the scaffold against movement.
p.2
Remote Interorgan Communication
What is the significance of the Remote Sensing and Signaling Hypothesis in uremic syndrome?
It provides a framework for understanding metabolic and signaling aberrations in the context of interorgan communication.
p.1
SLC and ABC Transporters
What types of transporters are emphasized in the Remote Sensing and Signaling Hypothesis?
Multispecific drug transporters and more selective SLC transporters.
p.3
Genetic Disorders Related to Amino Acid Transport
What condition is associated with the EAAT3 transporter?
Dicarboxylic amino aciduria.
p.8
Renal Amino Acid Transporters
What is the significance of SGLT2 in the kidneys?
Mediates glucose reabsorption in the early proximal tubule.
p.1
Remote Interorgan Communication
What is the significance of the gut-liver-kidney axis in health and disease?
It is involved in remote interorgan and interorganismal communication through differentially expressed transporters.
p.8
Renal Amino Acid Transporters
What is the role of collectrin in the kidneys?
Involved in kidney development and vesicle exocytosis.
p.6
Therapeutic Approaches for Uremic Syndrome
What treatments are recommended for managing urolithiasis in cystinuria?
Tiopronin, potassium citrate, reduction of animal protein intake, and increased nocturnal fluid intake.
p.3
Renal Amino Acid Transporters
What amino acids does the b0,+AT transporter transport?
Arginine, lysine, ornithine, cystine, methionine, leucine, and alanine.
p.4
Renal Amino Acid Transporters
What is the role of the amino acid transporter B0AT1?
It transports all neutral amino acids in symport with Na+.
p.8
Therapeutic Approaches for Uremic Syndrome
How does empagliflozin affect kidney disease in type 2 diabetes?
It slows the progression of kidney disease.
p.3
Renal Amino Acid Transporters
What is the function of the B0AT1 transporter?
It transports all neutral amino acids.
p.7
SLC and ABC Transporters
What are the three different protein folds of plasma membrane amino acid transporters?
LeuT-fold, Glt-fold, and multifacilitator superfamily (MFS)-fold.
p.4
Genetic Disorders Related to Amino Acid Transport
What is the significance of mutations in the SLC6A19 gene?
More than 20 different causative mutations have been identified, affecting amino acid transport.
p.2
Renal Amino Acid Transporters
What are the four major renal transport pathways for amino acids?
Transporters for neutral amino acids, cationic amino acids and cystine, anionic amino acids, and glycine and proline.
p.2
Pathophysiology of Chronic Kidney Disease (CKD)
What role do renal amino acid transporters play in metabolic diseases?
They are crucial for understanding renal metabolite reabsorption and the effects of inherited defects.
p.1
Remote Interorgan Communication
What systems does the Remote Sensing and Signaling Hypothesis interact with?
It interacts with neuroendocrine, growth factor cytokine, and autonomic nervous systems.
p.6
Uremic Syndrome and Metabolite Regulation
What happens to plasma levels of cationic amino acids in LPI?
They are reduced, affecting urea cycle function.
p.4
Transport Mechanisms in the Kidney
What proteins assist the B0AT1 transporter in the kidney?
Collectrin (TMEM27) facilitates B0AT1 trafficking to the apical membrane.
p.4
Genetic Disorders Related to Amino Acid Transport
What is iminoglycinuria?
A rare disorder where proline, glycine, and hydroxyproline are found in the urine.
p.5
Renal Amino Acid Transporters
What is the role of the taurine transporter TauT (SLC6A6)?
It mediates the reabsorption of taurine in the kidney.
p.6
Transport Mechanisms in the Kidney
What is the role of AGT1 in amino acid transport?
It operates as a cystine transporter, exchanging cystine for glutamate.
p.8
Renal Amino Acid Transporters
What is the role of ancillary proteins in renal amino acid transporters?
They facilitate the exit of the complex from the endoplasmic reticulum.
p.2
Genetic Disorders Related to Amino Acid Transport
What disorder is associated with the transporter for anionic amino acids?
Dicarboxylic aminoaciduria.
p.2
Drug-Metabolite Interactions
How do drug-metabolite interactions (DMI) affect metabolic pathways?
Competition for transport can affect a wide range of metabolic pathways, not just those directly involving the transporter.
p.8
Genetic Disorders Related to Amino Acid Transport
What happens when there are defects in Na+/glucose cotransporter (SGLT1)?
It causes glucose-galactose malabsorption.
p.5
Genetic Disorders Related to Amino Acid Transport
What is the significance of aminoaciduria in cystinuria?
It indicates a shared transporter for cationic amino acids and cystine.
p.5
SLC and ABC Transporters
What is the relationship between SIT1 (SLC6A20) and amino acids?
SIT1 accepts amino acids with secondary, tertiary, or quaternary amines and is Na+ and Cl- dependent.
p.3
Renal Amino Acid Transporters
What are the two main types of tubules in the kidney where amino acid transporters are found?
Proximal convoluted tubule (PCT) and proximal straight tubule (PST).
p.3
Renal Amino Acid Transporters
What is the role of rBAT in amino acid transport?
It serves as an ancillary subunit for other transporters.
p.7
Transport Mechanisms in the Kidney
What role does the leucine side chain play in the LeuT protein fold?
It occupies the empty binding site, facilitating the transition back to the outside conformation.
p.7
SLC and ABC Transporters
What is the function of members of the SLC22 family?
They are nonspecific anion transporters that may serve as efflux pathways for glutamate.
p.4
Renal Amino Acid Transporters
What is the role of PAT2 (SLC36A2) in amino acid transport?
It is involved in the combined action for the transport of proline, glycine, and hydroxyproline.
p.5
Renal Amino Acid Transporters
What is the role of SNAT3 (SLC38A3) in the kidney?
It transports glutamine, asparagine, and histidine, and is upregulated during chronic acidosis.
p.7
Transport Mechanisms in the Kidney
What is the occluded conformation in transporter proteins?
It is the state where the transporter encloses the substrate before transitioning to release it.
p.4
Genetic Disorders Related to Amino Acid Transport
What disorder is associated with the aminoaciduria observed in Hartnup disorder?
Hartnup disorder is restricted to neutral amino acids.
p.4
Renal Amino Acid Transporters
What is the function of the high-affinity transporter B0AT2?
It has a strong preference for branched-chain amino acids and methionine with substrate affinities < 100 μM.
p.3
Renal Amino Acid Transporters
What is the function of the EAAT3 transporter?
It transports glutamate, aspartate, and cystine.
