L6 Organic Solute Transport II Flashcards
neutral amino acids + transport and reabsorption mechanism
neutral amino acids: alanine, phenylalanine, asparagine, glutamine, histidine, isoleucine, serine, threonine, tryptophan, tyrosine, valine
- transport mechanism: energy of sodium gradient going in through apical membrane provides energy for uphill absorption of neutral amino acids (same as for glucose)
- reabsorption of β-alanine occurs by cotransport with H⁺ in S1 and with Na⁺ in S3
acidic (anionic) amino acids + transport mechanism
acidic (anionic) amino acids: glutamate, aspartate
- coupled to both Na⁺ and H⁺
basic (cationic) amino acids + cystine transport mechanism
basic (cationic) amino acids + cystine: lysine, arginine, ornithine, cystine (dimer of two cysteine amino acids joined by disulfide bond)
- exchanger process in which neutral amino acids get secreted for basic amino acid to get reabsorbed
- independent of Na⁺
glycine, proline, and hydroxyproline transport mechanism
glycine, proline, and hydroxyproline
- reabsorbed with H⁺
Hartnup disease cause and symptoms
defect in neutral amino acid reabsorption → Hartnup disease: skin rash, cerebellar ataxia
cystinuria cause and symptoms
defect in cystine reabsorption → cystinuria: kidney stones, low grade chronic pain, tiredness, depression, unquenchable thirst, irritability, mood swings
carboxylic acids transport mechanisms through apical membrane vs basolateral membrane
carboxylic acids
apical membrane
- monovalent carboxylates (eg. lactate⁻): 2 Na⁺ : 1 anion
- di- and trivalent (eg. ɑ-ketoglutarate²⁻, citrate³⁻): 3 Na⁺ : 1 anion
basolateral membrane
- H⁺ cotransport
- organic anion transport
- exercise, epilepsy, hypothermia → ↑ ______
- fasting, diabetes mellitus → ↑ ___
acids
- exercise, epilepsy, hypothermia → ↑ lactic acid
- fasting, diabetes mellitus → ↑ ketoacids
formate = ___ (chemical formula)
- present at ___ concentrations in plasma + ultrafiltrate ( ~ ___ mM)
- formate and ___ enter ___ tubule cells via carriers
- H⁺ is exchanged for luminal ___ (via ___)
- formate is exchanged for luminal ___ (via ___/___)
- the recycled formate then repeats the process → support more ___ entry (reabsorption) (with little amounts of formate)
- ___/___ exchangers can also transport formate
formate = HCOO⁻
- present at low concentrations in plasma + ultrafiltrate ( ~ 0.3 mM)
- formate and H⁺ enter proximal tubule cells via carriers
- H⁺ is exchanged for luminal Na⁺ (via NHE3)
- formate is exchanged for luminal Cl⁻ (via CFEX/SLC)
- the recycled formate then repeats the process → support more NaCl entry (reabsorption) (with little amounts of formate)
- oxalate/Cl⁻ exchangers can also transport formate
urate
- end product of ___ metabolism → ___% gets reabsorbed
reabsorption in S1 and S2 via:
- ___ (simple diffusion paracellularly)
- ___ with intracellular ___, ___, ___, or ___ or ___
secretion in S2 by:
- basolateral exchangers ___ and ___ and apical channel ___ → fine tunes amount of ___
- URAT 1 mutations → ___ (not enough ___)
- UAT mutations → ___ (not enough ___)
- explain urate solubility
- hyperuricemia causes
urate
- end product of purine metabolism → 90% gets reabsorbed
reabsorption in S1 and S2 via:
- URAT1 (simple diffusion paracellularly)
- exchange with intracellular OH⁻, Cl⁻, PAH, or mono- or di-carboxylates
secretion in S2 by:
- basolateral exchangers OAT1 and OAT3 and apical channel UAT → fine tunes amount of reabsorption
- URAT 1 mutations → hypouricemia (not enough reabsorption)
- UAT mutations → gout (not enough secretion)
- urate: low solubility ; solubility is lower at low temperature or low pH → urate crystallization
- impaired secretion = unopposed reabsorption → ↑ Tm →↑ hyperuricemia
PAH (para-aminohippurate)
- normally produced by the body or not? why is it used?
- clearance of PAH (CPAH) = ?
- ______ is required because some bind to albumin + are not filtered
- secretion occurs ___ net electrochemical gradient in S2 and S3
- how does PAH exit through apical membrane occur?
PAH (para-aminohippurate)
- is not normally produced by body, but widely for naturally-occuring acids + anionic drugs
- clearance of PAH (CPAH) = effective renal plasma flow
- active secretion is required because some bind to albumin + are not filtered
- secretion occurs against net electrochemical gradient in S2 and S3
- exit through apical membrane is mediated by carrier-mediated anion exchange (urate-anion exchanger) → saturable, intracellular dicarboxylic acids are exchanged for PAH
organic cations
- secreted in ___ segment
- basolateral uptake through ______ through ___
- apical efflux is through ______
organic cations
- secreted in S3 segment
- basolateral uptake through facilitated diffusion through OCT1
- apical efflux is through H⁺/organic cation exchange
urea
- [𝑢𝑟𝑒𝑎]𝑝𝑙𝑎𝑠𝑚𝑎 ~ ___-___ mM
- also called ______ or ___
- reabsorbed in ___ and ___ ___ ___
urea reabsorbed ___ its concentration gradient after ___ is reabsorbed
- permeability of tubule wall to urea is ___ (<, >?) than to water → ___ (<, >?) urea leaves tubule than water → its concentration ___ in lumen
- ↑ water reabsorption → ___ urea concentration in tubule (___ [ ] gradient) → ___ urea reabsorption → ___ urea excretion
- ↓ water reabsorption → ___ urea concentration in tubule (___ [ ] gradient) → ___ urea reabsorption → ___ urea excretion
- permeability in inner medullary collecting duct is stimulated by ___
- urea recycles in ___ - loops back into loop of Henle
- ___% of filtered urea is excreted at low flow rates
- ___% excreted at high flow rates
explain! : → clinical fall in urine flow rate → excretion of urea is more impaired than can be attributed to fall in GFR
urea
- [𝑢𝑟𝑒𝑎]𝑝𝑙𝑎𝑠𝑚𝑎 ~ 3 − 9 mM
- also called Blood Urea Nitrogen or BUN
- reabsorbed in S3 and medullary collecting duct
urea reabsorbed down its concentration gradient after water is reabsorbed
- permeability of tubule wall to urea is less than to water → less urea leaves tubule than water → its concentration increases in lumen
- ↑ water reabsorption → ↑ urea concentration in tubule (strong [ ] gradient) → ↑ urea reabsorption → ↓ urea excretion
- ↓ water reabsorption → ↓ urea concentration in tubule (weak [ ] gradient) → ↓ urea reabsorption → ↑ urea excretion
- permeability in inner medullary collecting duct is stimulated by ADH
- urea recycles in medulla - loops back into loop of Henle
- only 20% of filtered urea is excreted at low flow rates
- 70% excreted at high flow rates (no time for urea to cross epithelium)
→ clinical fall in urine flow rate: ↓ GFR → less urea is filtered AND ↓ urine flow → ↑ water reabsorption → ↑ urea concentration in the tubule → steeper gradient for urea reabsorption → ↑↑ urea reabsorption
what is the plasma [urea] : [creatinine] concentration ratio an indicator of? why?
plasma [urea] : [creatinine] concentration ratio
- useful indicator of effective blood volume and renal perfusion
- creatinine excretion only depends on GFR (not flow rate - not reabsorbed and minimally secreted)
- urea excretion depends on flow rate (reabsorption increases at low flow rates)
↓ effective blood volume / ↓ renal perfusion
→ ↓ GFR
→ ↓ urine flow
→ ↑ urea reabsorption
→ ↑ plasma urea > creatinine
→ ↑ urea : creatinine ratio
small proteins + oligopeptides
- glomerular barrier restricts proteins > ___ kDa
- however, some ___, ___, and small proteins (ex. ___, ___ binding proteins, etc) are filtered and must be reabsorbed
mechanisms for protein recovery of small proteins and oligopeptides? (3)
small proteins + oligopeptides
- glomerular barrier restricts proteins > 10 kDa
- however, some albumin, immunoglobulins, and small proteins (ex. hormones, vitamin binding proteins, etc) are filtered and must be reabsorbed
mechanisms for protein recovery:
1. oligopeptides are hydrolyzed by brush border enzymes into amino acids → reabsorbed coupled to sodium
2. short peptides reabsorbed by oligopeptide cotransporter which carry proteins and oligopeptides in same direction
- gradient favors entry of protons into a cell
- get broken down by proteases and efflux out basolateral membrane
3. receptors (megalin and cubilin) on apical membrane bind to proteins and endocytose them
- acidification of lysosome allows degradation of protein into amino acids which can flux out of the cell
weak acids + bases
- e.g.: ______
- passive transport occurs by ___-___ diffusion and is modulated by transtubular ___ gradients
example: weak acid HA
- only ___ form of acid (uncharged, lipophilic) can diffuse across cell membrane of tubule
- → net transport of HA across epithelium proceeds according to the concentration gradient
- If pH is higher in tubular fluid: HA → ___ + ___ → ___
- If pH is lower in tubular fluid: ___ + ___ → ___ → ___
weak acids + bases
- e.g.: many drugs
- passive transport occurs by non-ionic diffusion and is modulated by transtubular pH gradients
example: weak acid HA
- only undissociated form of acid (uncharged, lipophilic) can diffuse across cell membrane of tubule
- → net transport of HA across epithelium proceeds according to the concentration gradient
- if pH is higher in tubular fluid: HA → H⁺ + A⁻ → less HA in tubule and ionic form can’t be reabsorbed os more excretion of ionic form
- if pH is lower in tubular fluid: H⁺ + A⁻ → HA → more HA in tubule so it is reabsorbed
