Molecular Basis for the Substrate Specificity of Human Catecholamine Sulfotransferase, SULT1A3

Abstract

Sulfation is an important component of the body’s chemical defence mechanism, and provides a major route for the metabolism, detoxification and elimination of a host of xenobiotics (Coughtrie 1996). In addition to this role, sulfation also functions in the homeostasis of a number of important endogenous compounds, including iodothyronines (Visser 1996), steroid hormones (Roy 1992), oxysterols (Javitt et al. 2001) and catecholamines (Goldstein et al. 1999). These reactions are catalysed by members of the sulfotransferase (SULT) enzyme superfamily that transfer a sulfuryl moiety from the co-substrate 3′-phopshoadenosine 5′-phosphosulfate (PAPS). In humans, the SULT family numbers at least 11 members derived from at least 10 genes. The human SULTs can be subdivided into 3 different subfamilies based on amino acid sequence similarity and functional activity, and the largest family, SULT1 or phenol SULT, currently comprises 7 members (Coughtrie et al. 2001). Humans (and other primates) differ from most animal species in that they have significant levels of circulating catecholamine sulfates; for example up to 98% of circulating dopamine is in its sulfated form (Goldstein et al. 1999). It is believed that the gastrointestinal tract is the major source of these circulating catecholamine sulfates (Goldstein et al. 1999), and indeed significant increases in plasma dopamine sulfate can be observed after ingestion of bananas (Davidson et al. 1981) which are rich in dopamine (Kanazawa et al. 2000).