GLDC是在研究人員調(diào)查一類(lèi)稱(chēng)作為“先天性代謝缺陷”(inborn errors of metabolism)的疾病時(shí)引起他們的注意的。當(dāng)細(xì)胞中缺失某些代謝酶時(shí)，便會(huì)發(fā)生這類(lèi)疾病。其中許多尤其影響了腦發(fā)育;最常見(jiàn)的一種就是苯丙酮尿癥(Phenylketonuria,P KU)，特征是無(wú)法分解氨基酸苯丙氨酸。這樣的患者必須避免食用苯丙氨酸，以預(yù)防智力障礙和癲癇發(fā)作等問(wèn)題。
原文摘要：Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment1, 2, 3. Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumour environment, but also renders these cells sensitive to glycine cleavage system inhibition.
