L3: Transporters Flashcards
What are the two main types of active transporters?
- Primary active transporters:
- Uses ATP energy directly.
- ATPases or ATP-powered pumps drive the process.
- Moves ions/molecules against their concentration gradient.
Example: Sodium-potassium pump (Na+/K+-ATPase). - Secondary active transporters:
- Uses pre-existing ion gradients to move solutes against their CG
- Co-transporters or symporters drive the process.
- Two types: Symport (same direction) and Antiport (opposite direction).
Example of Symport: Sodium-glucose co-transporter (SGLT).
Example of Antiport: Sodium-calcium exchanger.
What is the primary source of energy for primary active transporters?
ATP (adenosine triphosphate) hydrolysis
Give an example of a primary active transporter
- the Na+/K+-ATPase, which pumps sodium ions out of the cell and potassium ions into the cell
How do secondary active transporters use energy to transport ions against their concentration gradient?
- Secondary active transporters use energy generated by an ion moving down its CG to transport another ion against its CG
- process is also known as COUPLED TRANSPORT
What are the three main functions of transporters?
- maintain concentration gradients
- provide nutrients to the cell
- reuptake neurotransmitters
How many superfamilies of transporters are there, and what are they?
There are two superfamilies of transporters:
- plasma membrane superfamily, which is divided into two families:
a. Na+/Cl- (SLC6) family: Consists of 12 transmembrane domains, is electroneutral, and includes subfamilies like SERT, NET, DAT, GABAT, and GlyT. The cotransport of Na+ & Cl- into the cell provides energy for the transport of NTs
b. Na+/K+ (SLC1a) family: Comprises 6-10 transmembrane domains and includes the subfamily EAAT, which transports glutamate & aspartate. The counter transport of Na+ and K+ provides energy for the uptake of excitatory NTs into the cell. It is electrogenic & alters the electro potential of the cell as it also transports one OH- ion out of the cell
How many families of vesicular transporters are there, and what neurotransmitters do they transport?
There are four families of vesicular transporters:
- VMAT1 and VMAT2: Transport 5-HT, DA, NA, and histamine. VMAT1 is found in endocrine cells, and VMAT2 is found in neuronal cells. Both have 12 transmembrane domains.
- VAchT: Transports Ach. It has 12 transmembrane domains, a large extracellular loop, and its N and C terminals are on the inside of the cell.
- VIAAT: Transports GABA and glycine. It has 10 transmembrane domains, with the long N and short C terminal located internally.
- Vglut1-3: Transports glutamate
How is the H+ gradient maintained in vesicular transporters?
- by the H+ATPase, which pumps H+ into the cell
- The vesicular transporters use the counter transport of H+ down the CG out of the cell to transport NT into the cell
How does the affinity of vesicular transporters compare to plasma membrane transporters?
- The vesicular transporters have a relatively lower affinity compared to the plasma membrane transporters, resulting in a lower Km (Michaelis-Menten constant)
What is the glutamate, glutamine shuttle?
- a process that terminates the actions of glutamate
- Glutamine serves as the precursor of GABA, providing a mechanism for regulating the levels of these neurotransmitters
How is glutamate taken up by glial cells and converted to glutamine?
- via the EAAT2 transporter
- Inside the glial cell, glutamate is converted to glutamine through the enzyme glutamine synthase
How does glutamine move out of the glial cell and enter the neuronal cell?
- glutamine moves out of the glial cell via the amino acid transporter N
- then enters the neuronal cell via the amino acid transporter A
What enzymes are involved in the conversion of glutamine to glutamate in the neuronal cell?
- inside the neuronal cell, glutamine is converted to glutamate through the enzyme glutaminase
What are the different types of glutamate transporters and where are they primarily found?
EAAT1: Found primarily in glial cells.
EAAT2: Found in glial cells and some neurons.
EAAT3 and EAAT4: Found primarily in neuronal cells, with isoform 3 also present in GABAergic neurons.
EAA5: Found in retinal cells
How does the affinity of EAAT2 compare to the vesicular transporter Vglut1-3?
- EAAT2 has a higher affinity than the vesicular transporters Vglut1-3, with a Km (Michaelis-Menten constant) in the low μM range compared to Vglut1-3’s Km of 1mM
