Macromolecular Transport

00:01 Now, let’s go ion by ion through these processes of transport.

00:06 Glucose Remember I said, almost all of glucose is reabsorbed in the first 25 percent of the proximal tubule.

00:16 How does this happe? Well, we have 2 transporters involved.

00:20 The SGLT2 is a transporter that will move both sodium and glucose across the apical membrane.

00:27 Why does sodium travel with glucose at this particular transporter? It’s all because of that sodium-potassium ATPase on the basolateral side.

00:36 That pump sets up the driving force.

00:39 And so sodium is actually used, in this case, as energy to move across the glucose molecule across the apical membrane.

00:47 Then glucose leaves the basolateral membrane by a different transporter known as a GLUT2.

00:56 The majority of the particular transporters, or amounts of glucose, will be reabsorbed by this SGLT2.

01:06 There’s a very small amount though that escapes past the SGLT2, and that’s usually picked up by the SGLT1.

01:15 This transporter is less quick in transporting things across the apical membrane, but it has a very high affinity.

01:25 So it’s a good clean-up molecule to transport the last few things across.

01:31 So this SGLT1 is the clean-up one, and the SGLT2 is the big work horse to get most of the glucose across the apical membrane.

01:42 Later on in this SGLT1 scenario, you use a different GLUT molecule to get the glucose across the basolateral membrane.

01:52 It’s known as a GLUT1.

01:55 So SGLT2 is linked with GLUT2 and SGLT1 is linked to GLUT1.

02:05 Now, peptides, again, are reabsorbed very quickly across the proximal tubule and are pretty much all reabsorbed by the time you end the proximal tubule.

02:17 How does this occur? Well, you have things like di- and tripeptides, even amino acids that are being traveled down the renal tubule because these are all freely filtered.

02:28 Then you use a PepT1 transporter to move across the small peptide.

02:34 It’s further broken down within the cell, and then each individual amino acid is transported out of the basolateral side, and that will yield amino acids in the interstitial fluid that then will get picked up by the blood.

02:50 Now, there are also some little bit larger peptides, maybe tripeptides, maybe they’re a little bit bigger than that, that can be broken down by peptidases.

02:59 After they are broken down, then they can be trans across by this PepT1.

03:06 Further broken down in the cytosol, and then individual amino acids kicked out across the basolateral membrane.

03:14 Now, we go to the late segment of the proximal tubule.

03:17 Here, any extra or few amounts of di- and tripeptides that make it past the PepT 1 are then cleaned up by the PepT2.

03:27 The PepT2 transporter also uses hydrogen ions to co-transport those peptides across into the cytosol.

03:35 They are further broken down by cytosol enzymes, and then individual amino acids are moved out of the basolateral membrane, into the interstitial fluid, and picked up by the blood.

03:47 Now, there are proteins that also are freely filtered.

03:50 Now, they have to be pretty small proteins to make it through the glomerular barrier.

03:54 But if they are small proteins, they can be reabsorbed in the late segment.

03:59 These are done by an endocytic vesicle process that involves a couple of receptors.

04:05 Megalin receptors and cubilin receptors are the processes that will bind to the protein, and then bud off and move into the cell.

04:14 Once they are in the cell, they will continue to migrate over to the basolateral side, and then they will spill out their contents.

04:23 Once their contents are spilled out on the opposite side in terms of the basolateral membrane, they can be reabsorbed.

04:32 Usually, there’s some enzymatic breakdown that does occur of these peptides into tripeptides and even some amino acids, but it’s not as complete of a process that is done by the di- and tripeptides.

04:49 So to go through how amino acids are transported – because we’ve already dealt with tripeptides, dipeptides, and small proteins – the amino acid transporters will be very dependent upon which type of amino acid it is.

05:05 If it’s an acidic amino acid, it gets used by one transport system.

05:09 Basic amino acids are transported by another.

05:12 And finally, the neutral amino acids are usually co-transported with either sodium or hydrogen ions.

05:20 To get across the basolateral membrane, it is the basic amino acids and the neutral that are transported across with sodium, while you have the aromatic amino acids that actually can get across through facilitated diffusion.

05:37 So it depends on what amino acid classification that we’re in, in terms of its biochemistry, how individually it gets transported across either the apical or basolateral membrane.

05:52 Now, what happens to other ions, such as phosphate? Phosphate is a fairly charged molecule.

06:00 In this case, it needs a transporter to help get it across the apical membrane.

06:06 The example that we first are looking at here involves where there’s no transport of phosphate.

06:13 You might ask, what situations would you have a very little transport of phosphate across the apical membrane? And the answer is, when parathyroid hormone is high in the blood, it binds to a parathyroid hormone receptor, and that stops the transport of phosphates across the apical membrane.

06:32 When parathyroid hormone levels are low, there are transporters that are expressed on the apical membrane.

06:41 A few different types – but these 2 different types of transporters involves sodium as the co-transporter molecule.

06:50 And then through a mechanism that we don’t understand so well right now is also transported across the basolateral membrane.

06:59 So phosphate is transported across when parathyroid hormones are low.

07:05 When parathyroid hormone level is high, phosphate will be urinated out or excreted.

07:13 Where does parathyroid hormone come? It comes from the thyroid gland.

07:18 So the thyroid and the parathyroid are released at the same spot.

07:23 What does the parathyroid hormone do? It primarily works in the kidney to decrease phosphate absorption.

07:33 It will increase calcium reabsorption.

07:35 And finally, it helps to increase bone reabsorption.

07:41 All of the total goal of parathyroid hormone is to increase the plasma concentration of calcium.