Kojima Masayasu, Hamamoto Akie, Sato Takahiro
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka, Japan.
J Biochem. 2016 Oct;160(4):189-194. doi: 10.1093/jb/mvw046. Epub 2016 Aug 3.
In the gastric peptide hormone ghrelin, serine 3 (threonine 3 in frogs) is modified, primarily by n-octanoic acid; this modification is essential for ghrelin's activity. The enzyme that transfers n-octanoic acid to Ser3 of ghrelin is ghrelin O-acyltransferase (GOAT). GOAT, the only enzyme known to catalyze acyl modification of ghrelin, specifically modifies serine (or threonine) at the third position and does not modify other serine residues in ghrelin peptides. GOAT prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach the n-octanoyl form is the predominant form of acyl-modified ghrelin. GOAT is a promising target for drug development to treat metabolic diseases and eating disorders.
在胃肽激素胃饥饿素中，丝氨酸3（青蛙中为苏氨酸3）主要被正辛酸修饰；这种修饰对于胃饥饿素的活性至关重要。将正辛酸转移至胃饥饿素丝氨酸3的酶是胃饥饿素O-酰基转移酶（GOAT）。GOAT是已知唯一催化胃饥饿素酰基修饰的酶，它特异性修饰第三位的丝氨酸（或苏氨酸），而不修饰胃饥饿素肽中的其他丝氨酸残基。尽管在胃中，正辛酰形式是酰基修饰胃饥饿素的主要形式，但GOAT更倾向于以正己酰辅酶A而非正辛酰辅酶A作为酰基供体。GOAT是治疗代谢疾病和饮食失调药物开发的一个有前景的靶点。
