ABSTRACT
Kratom is a herbal and natural dietary supplement from Southeast Asia that is gaining popularity in the United States. Its leaves contain multiple psychoactive chemicals that stimulate opioid, alpha-2, and serotonergic receptors. Kratom is used as a stimulant and in the treatment of anxiety, pain, and opioid withdrawal. In most states, kratom can be purchased legally and is sold at smoke shops, gas stations, and online. To date, only limited data is available on the impact of habitual kratom use on patients undergoing anesthesia. The following case report highlights multiple anesthetic challenges posed by a heavy kratom user.
ABSTRACT
GoLoco motif proteins act as guanine nucleotide dissociation inhibitors (GDIs) for G-protein alpha subunits of the adenylyl cyclase-inhibitory (Galpha(i/o)) class. Rap1GAP2 is a newly identified GoLoco motif- and RapGAP domain-containing protein, and thus is considered a potential integrator of heterotrimeric and monomeric GTPase signaling. Primary sequence analysis indicated that the Rap1GAP2 GoLoco motif contains a lysine (Lys-75), rather than an arginine, at the crucial residue responsible for binding the alpha and beta phosphates of GDP and exerting GDI activity. To determine the functional outcome of this sequence variation we conducted a biophysical analysis of the human Rap1GAP2b/c GoLoco motif. We found that human Rap1GAP2b/c was deficient in GDI activity and Galpha interaction capability. Mutation of lysine-75 to arginine could not regain functional activity of the Rap1GAP2b/c GoLoco motif. Thus, the Rap1GAP2b/c GoLoco motif can be classed as inactive towards Galpha subunits. We also found that the Rap1GAP1a GoLoco motif, which lacks seven N-terminal amino acid residues present in canonical GoLoco motifs, does not interact with Galpha(i1). In contrast, the GoLoco motif of Rap1GAP1b, which is canonical in primary sequence, was found to interact with Galpha(i1).GDP.
