WEEK 10: PT 2

Question 1

Flashcard 1
Q: What is the primary function of EAATs in the CNS?

Answer 1

A: To clear glutamate from the synaptic cleft, preventing excitotoxicity and allowing synaptic reset.

Question 2

Flashcard 2
Q: What ion coupling stoichiometry is used by EAATs?

Answer 2

A: 1 glutamate⁻, 3 Na⁺, and 1 H⁺ into the cell, and 1 K⁺ out.

Question 3

Flashcard 3
Q: What makes EAATs “dual function” transporters?

Answer 3

A: They also allow Cl⁻ conductance, uncoupled from glutamate transport.

Question 4

Flashcard 4
Q: What is the physiological role of the Cl⁻ channel in EAATs?

Answer 4

A: Maintains charge neutrality and osmotic balance during glutamate uptake.

Question 5

🔹 Structure of GltPh
Flashcard 5
Q: What is GltPh and why is it important?

Answer 5

A: A Na⁺-dependent aspartate transporter from Pyrococcus horikoshii, used as a structural model for human EAATs.

Question 6

Flashcard 6
Q: Describe the structure of GltPh.

Answer 6

A: A trimer, with each subunit capable of transport; structurally similar to human EAAT2.

Question 7

Flashcard 7
Q: What is the “elevator mechanism” in GltPh?

Answer 7

A: The substrate-binding domain moves up/down across the membrane, carrying the bound substrate.

Question 8

Flashcard 8
Q: What is L-TBOA and how does it affect GltPh?

Answer 8

A: A competitive inhibitor that mimics glutamate and locks the transporter in a non-functional state.

Question 9

🔹 Transport Mechanisms & Experimental Insights
Flashcard 9
Q: What experimental method helped reveal GltPh’s Cl⁻ channel function?

Answer 9

A: Cryo-EM and cysteine cross-linking showed a Cl⁻ conducting state at the interface of transport and scaffold domains.

Question 10

Flashcard 10
Q: What is the significance of the “ClCS” state?

Answer 10

A: It represents the Cl⁻ conducting state between intermediate and inward-facing conformations.

Question 11

🔹 Glucose Transporters (GLUT1 – MFS Transporters)
Flashcard 11
Q: What is GLUT1 and how does it function?

Answer 11

A: A glucose uniporter in the MFS family that uses facilitated diffusion to transport glucose down its gradient.

Question 12

Flashcard 12
Q: What is the transport mechanism used by GLUT1?

Answer 12

A: Alternating access model: GLUT1 cycles through inward- and outward-facing conformations.

Question 13

Flashcard 13
Q: What is unique about the structure of GLUT1?

Answer 13

A: It has 12 transmembrane domains arranged in 2 bundles of 6, and a central latch structure to control gate closure.

Question 14

Flashcard 14
Q: How is glucose reabsorbed in the kidney?

Answer 14

A: By SGLT1/2, sodium-dependent cotransporters in the nephron, which work against the glucose gradient.

Question 15

Flashcard 15
Q: What is a key difference between EAATs and GLUT1 in terms of energy use?

Answer 15

A: EAATs are secondary active transporters (use Na⁺ gradient); GLUT1 is a passive uniporter (no energy needed).