Transporters in the GI System - Drewes

Question 1

What is the general control of the four basic processes in the GI System (digestion, absorption, secretion, motility)?

Answer 1

• Digestion, Absorption – not directly controlled processes
• Secretion, Motility – under neural and hormonal control

Question 2

What are the fundamental mechanisms of membrane transport?

Answer 2

• Passive Transport
  
  • Simple diffuse
    
    • e.g. alcohol
  • Facilitative diffusion
    
    • Pores
    • Gated Channels
    • Carrier
• Active transport
  
  • Carrier (uses ATP)

Question 3

How many GLUT transporters are there? What ones are important in the GI system?

Answer 3

• 14 total
• Important for GI:
  
  • GLUT2
  • GLUT5

Question 4

How many transmembrane segments does a membrane transporter typically have?

Answer 4

12

Question 5

What are the specific mechanisms used to absorb nutrients in the GI system (mainly small intestine)?

Answer 5

• Specific, transport of nutrients and water occurs primarily in the jejunum
• Active (secondary) transport-apical side
• Carrier-mediated-basolateral side
• Active (ABC-type)-both sides
• Significant excess in capacity
  
  • abundance of transporters
• Ileum can be called on for absorption
• Transverse colon reclamation of fluids, electrolytes, and bile acids

Question 6

What are the two distinct processes that establish an osmotic gradient that pulls water into the lumen of the intestine?

Answer 6

• 1. Increases in luminal osmotic pressure result from influx and digestion of foodstuffs.
• 2. Crypt cells actively secrete electrolytes, leading to water secretion.
     * CFTR and cholera and chloride efflux and diarrhea

Question 7

What is the single most important process that takes place in the small gut to make absorption possible?

Answer 7

establishment of an electrochemical gradient of sodium across the epithelial cell boundary of the lumen

Question 8

What specific lactate transporter is responsible for transport of butyrate to colonocytes and has been identified as a cancer suppressor gene in the colon?

Answer 8

MCT1-monocarboxylic acid transporter-1

Question 9

What kind of transporters are involved in drug adsorption in the intestinal epithelia?

Answer 9

• Effluxers
  
  • P-gp = P-glycoprotein
  • MRP = Multidrug resistance associated protein
  • BCRP - Breast cancer related protein
• Transporters
  
  • MCT1
  • OATs
  • many others

Question 10

What additional ways is drug uptake regulated by other than specific transporters?

Answer 10

• Regulatory elements (promoter) controlling protein levels
• Genetic polymorphisms affecting activity
• Presence/co-administration of transport inhibitors
  
  • Drug or diet (grapefruit juice)

Question 11

What are three different modalities of intestinal nutrient sensing?

Answer 11

• (A) A taste receptor signals in EECs to affect incretin release, which, in turn, affects the expression or membrane availability of transporters in ECs.
  
  • brain signals to the gut
• (B) Possible modes of nutrient-coupled electrogenic transport in EECs or ECs.
• (C) Possible mechanisms by which nutrient binding to metabolic transceptors leads to incretin release (EECs) or changes in gene expression in ECs.