Defective SLC6A2 does not cotransport NAd, Na+ from extracellular region to cytosol

Stable Identifier
R-HSA-5659764
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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SLC6A2 encodes the sodium-dependent noradrenaline transporter NAT1 which terminates the action of the neurotransmitter noradrenaline (NAd) by transporting it from the synapse back to its vesicles for storage and reuse. SLC6A2 is expressed in the CNS and adrenal glands. Defects in SLC6A2 can cause orthostatic intolerance (OI; MIM:604715), a syndrome characterised by lightheadedness, fatigue and development of symptoms during upright standing, relieved by sitting back down again. Plasma NAd concentration is abnormally high. The loss-of-function A457P mutation in SLC6A2 can lead to OI. NAd is not transported back to vesciles for storage and builds up in the bloodstream (Shannon et al. 2000, Paczkowski et al. 2002).

Literature References
PubMed ID Title Journal Year
10684912 Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

Shannon, JR, Flattem, NL, Jordan, J, Jacob, G, Black, BK, Biaggioni, I, Blakely, RD, Robertson, D

N Engl J Med 2000
11875370 Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter

Paczkowski, FA, Bönisch, H, Bryan-Lluka, LJ

Pharmacogenetics 2002
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
norepinephrine:sodium symporter activity of SLC6A2 A457P [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
amino acid metabolic disorder 9252 inborn errors of amino acid metabolism
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