Ketoisovaleric acid (KIV) is as a precursor in leucine and valine synthesis[1]. Ketoisovaleric acid can serve as an initial compound in vitamin B5 biosynthesis of Escherichia coli[2]. Long-term high levels of Ketoisovaleric acid are associated with maple syrup urine disease (MSUD)[3, 4].
Ketoisovaleric acid (1 to 5mM; 1h) significantly reduced the content of nonenzymatic antioxidants in the cerebral cortex in vitro, thereby decreasing the antioxidant responsiveness of cortical cells[3]. Ketoisovaleric acid (5mM; 24h) moderately suppressed lymphocyte DNA synthesis, which caused an in vitro immunosuppression[5].
Ketoisovaleric acid (5μmol/2μl; intrahippocampal injection; 10min) was administered to male rat, which provoked rat learning deficits in the inhibitory avoidance task[6]. Ketoisovaleric acid (8μmol/2μl; intrastriatal administraion; 20min) could induce seizures in rats[7].
References:
[1] NSHIMIYIMANA P, LIU L, DU G. Engineering of L-amino acid deaminases for the production of alpha-keto acids from L-amino acids [J]. Bioengineered, 2019, 10(1): 43-51.
[2] CHASSAGNOLE C, DIANO A, LETISSE F, et al. Metabolic network analysis during fed-batch cultivation of Corynebacterium glutamicum for pantothenic acid production: first quantitative data and analysis of by-product formation [J]. J Biotechnol, 2003, 104(1-3): 261-72.
[3] BRIDI R, BRAUN C A, ZORZI G K, et al. alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats [J]. Metab Brain Dis, 2005, 20(2): 155-67.
[4] RABELO F, LEMOS I D S, DAL TOE C P, et al. Acute effects of intracerebroventricular administration of alpha-ketoisocaproic acid in young rats on inflammatory parameters [J]. Metab Brain Dis, 2023, 38(5): 1573-9.
[5] SCHLOTTFELDT J, BLAZINA L R, WANNMACHER C M, et al. The effect of organic acids on phytohaemagglutinin-activated proliferation of human lymphocytes in vitro [J]. Int J Immunopharmacol, 1995, 17(3): 175-82.
[6] DE CASTRO VASQUES V, DE BOER M A, DILIGENTI F, et al. Intrahippocampal administration of the alpha-keto acids accumulating in maple syrup urine disease provokes learning deficits in rats [J]. Pharmacol Biochem Behav, 2004, 77(1): 183-90.
[7] COITINHO A S, DE MELLO C F, LIMA T T, et al. Pharmacological evidence that alpha-ketoisovaleric acid induces convulsions through GABAergic and glutamatergic mechanisms in rats [J]. Brain research, 2001, 894(1): 68-73.
Ketoisovaleric acid（KIV）是亮氨酸和缬氨酸合成的前体[1]。Ketoisovaleric acid能够作为大肠杆菌维生素B5生物合成的初始化合物[2]。长期高水平的Ketoisovaleric acid与MSUD（maple syrup urine disease；枫糖浆尿病）有关[3, 4]。
Ketoisovaleric acid（1 to 5mM；1h）显著降低了体外脑皮层中非酶抗氧化剂的含量，从而降低了皮层细胞的抗氧化反应性[3]。Ketoisovaleric acid（5mM；24h）适度抑制了淋巴细胞DNA合成，引发免疫抑制[5]。
使用Ketoisovaleric acid（5μmol/2μl; intrahippocampal injection; 10min）注入雄性大鼠海马后，引起大鼠在抑制性回避任务中的学习缺陷[6]。使用Ketoisovaleric acid（8μmol/2μl; intrastriatal administraion; 20min）注入大鼠纹状体后，可以诱导大鼠惊厥[7]。