BIOL 2420 Lecture Notes - Lecture 7: Organic Anion-Transporting Polypeptide, Proximal Tubule, Bile Acid
26 Apr 2018
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Unit 7 – Lecture 7
Secretion
- secretion: the transfer of molecules from ECF into the lumen of the nephron
o depends mostly on membrane transport systems
- secretion of K+ and H+ by the distal nephron is important in the homeostatic regulation of those
ions
- many organic compounds are secreted
o these include metabolites produced in the body and substances brought into the body
(xenobiotics)
- enables the nephron to enhance excretion of a substance
o if a substance is filtered and not reabsorbed, it is excreted very efficiently
o if the substance is filtered into the tubule (not reabsorbed) and then more of it is
secreted into the tubule from the peritubular capillaries – excretion is even more
efficient
- an active process
o it requires moving substrates against their concentration gradients
o most organic compounds are secreted across the proximal tubule epithelium into the
lumen by indirect active transport
o look at how the tubule handles the secretion of organic anions
- transporters responsible for organic solute excretion have broad specificity
o example: organic anion transporter (OAT) family
▪ able to transport a wide variety of endogenous and exogenous anions
▪ bile salts to benzoate used as preservative in soft drinks, salicylate from aspirin,
artificial sweetener saccharine
▪ secretion of organic anions on the OAT is an example of tertiary active
transport, where the use of energy from ATP is two steps removed from the
OAT
- Steps of the OAT
1. Direct active transport – proximal tubule cell uses ATP to maintain the low
intracellular concentration of Na+
2. Na+ gradient is used to concentrate a dicarboxylate inside the tubule cell
▪ Using Na+-dicarboxylate cotransporter called the NaDC
▪ NaDC is found on both apical and basolateral membranes in the proximal tubule
▪ Dicarboxylates are the anion form of dicarboxylic acids
• Two carboxyl groups
• Most citric acid cycle intermediates are dicarboxylates
3. Concentration of dicarboxylate inside the tubule cell
▪ OAT is an indirect active transporter that uses the diacrbozylate moving out of
the cell down its concentration gradient to move an organic anion against its
gradient intothe cell
4. Apical transporters have not been definitely identified but appear to be anion
exchangers
▪ Occurs once the organic anion is concentrated inside the tubule cell
▪ It can use facilitated diffusion to enter the lumen
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