In the glutaminase II pathway (which we now refer to as the glutamine transaminase-ω-amidase (GTωA) pathway), l-glutamine is transaminated to α-ketoglutaramate (KGM), which, in turn, is hydrolyzed to α-ketoglutarate and ammonia by an enzyme known as ω-amidase. Despite the fact that the GTωA pathway was discovered more than 70 years ago, and is widespread in nature, the pathway has received limited attention. This is partly due to the broad amino acid/α-keto acid specificity of the glutamine transaminases, which has led to confusion over nomenclature and in assigning precise biological roles. Secondly, the α-keto acid product of glutamine transaminases – KGM – has not, until recently, become available in pure form. Here, we briefly discuss the metabolic importance of the GTωA pathway in microorganisms, plants and mammals. We pay special attention to the chemistry of KGM and methods for its synthesis. We discuss the importance of KGM as a biomarker for hyperammonemic diseases. We provide evidence that the GTωA pathway satisfies, in part, ‘glutamine addiction’ in a variety of cancer cells. We show that the anti-cancer drugs 6-diazo-5-oxo-l-norleucine and l-azaserine are transaminase and β-lyase substrates of glutamine transaminase K, respectively. We suggest that there is a pressing need for the development of: (1) inexpensive and scaled-up procedures for the synthesis of KGM to facilitate research on the biological importance of the GTωA pathway in mammalian and human tissues and in agricultural research; and (2) potent and selective inhibitors of ω-amidase, both as anti-cancer agents and as a means for investigating the detailed enzyme mechanism.

在谷氨酰胺酶 II 途径（我们现在称为谷氨酰胺转氨酶-ω-酰胺酶 (GTωA) 途径）中，l-谷氨酰胺转氨为 α-酮戊二酸 (KGM)，后者又被称为 ω-酰胺酶的酶水解为 α-酮戊二酸和氨。尽管 GTωA 通路已于 70 多年前发现，并且在自然界中广泛存在，但该通路受到的关注有限。这部分是由于谷氨酰胺转氨酶广泛的氨基酸/α-酮酸特异性，这导致了命名和精确生物学作用分配的混乱。其次，谷氨酰胺转氨酶的 α-酮酸产物 - KGM - 直到最近才以纯品形式出现。在这里，我们简要讨论 GTωA 途径在微生物、植物和哺乳动物中的代谢重要性。我们特别关注魔芋葡甘聚糖的化学及其合成方法。我们讨论了 KGM 作为高氨血症疾病生物标志物的重要性。我们提供的证据表明，GTωA 通路在一定程度上满足了多种癌细胞的“谷氨酰胺成瘾”。我们证明抗癌药物 6-diazo-5-oxo-L-正亮氨酸和L-重氮丝氨酸分别是谷氨酰胺转氨酶 K 的转氨酶和 β-裂解酶底物。我们建议迫切需要开发：（1）廉价且规模化的 KGM 合成方法，以促进 GTωA 途径在哺乳动物和人体组织以及农业研究中的生物学重要性的研究；(2) ω-酰胺酶的有效和选择性抑制剂，既可以作为抗癌药物，也可以作为研究详细酶机制的手段。