Vitamin B6-dependent and responsive disorders

Vitamin B6 is absorbed in different vitamers, which undergo several (de)phosphorylation steps, to be able to pas the blood-brain barrier. Within the brain, PLP (pyridoxal-P) is the only active cofactor for intracellular enzyme reactions. PLP catalyses over 100 reactions, mainly related to amino acids and neurotransmitter metabolism. Bold lines in the pathway diagram show how the major source of PLP is divided in the body. A number of genetic defects have been identified as the underlying cause of vitamin B6 dependent epilepsies, particularly occurring in the neonatal life stage, which could lead to irreversible brain damage or death. The disorders related to this pathway can be divided in two categories: reduced production/availability of PLP or inactivation of PLP by formation of Knoevenagel products. Specific biomarkers from urine, plasma or cerebrospinal fluid (CSF) exist to distinguish the disorders. Oral treatment with PL or PLP is available, as well as intrauterine treatment with vitamin B6 for mothers in the early stages of pregnancy. This pathway was inspired by Ed. 5 Chapter 34 of the book of Blau (ISBN 9783030677268) (ed.4 Chapter 11).

维生素B6吸收于多种异构体中，经过数个磷酸化（去磷酸化）步骤，方得以穿越血脑屏障。在脑内，PLP（吡哆醛-5-磷酸）为细胞内酶反应的唯一活性辅因子。PLP催化超过100种反应，主要涉及氨基酸和神经递质代谢。路径图中的粗线展示了PLP在体内的主要来源。已识别出多种遗传缺陷，作为维生素B6依赖性癫痫症的基础原因，尤其是在新生儿生命阶段，可能导致不可逆的脑损伤或死亡。与此途径相关的疾病可分为两类：PLP的生成/可用性降低或通过形成Knoevenagel产物而使PLP失活。尿液中、血浆或脑脊液中（CSF）存在特异性生物标志物，以区分这些疾病。目前已有PL或PLP的口服治疗，以及对于妊娠早期母亲的子宫内维生素B6治疗。本途径灵感来源于Blau所著《蓝氏手册》第五版第34章（ISBN 9783030677268）（第四版第11章）。