NAD biosynthesis II from tryptophan

As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate (see NAD biosynthesis I (from aspartate)). In eukaryotes, the de novo pathway starts with tryptophan (this pathway). The role of tryptophan as a precursor in eukaryotic NAD biosynthesis was first suggested by nutritional studies in which humans stricken with pellagra, a nicotinamide (niacine) deficiency disease, recovered after the addition of tryptophan or niacin to their diets [Krehl45]. Other studies established tryptophan as a precursor of NAD in many animal and plant systems [Foster80a]. This pathway is closely related to the catabolic pathway of tryptophan (tryptophan degradation I (via anthranilate)), suggesting an evolutionary link between the two. Though rare, the synthesis of NAD from tryptophan in prokaryotes has been observed in several organisms. Wilson and Henderson reported that Xanthomonas arboricola pv. pruni requires niacin for growth and can use tryptophan or 3-hydroxyanthranilic acid as a substitute [Wilson63]. Some members of the Actinomycete group were also reported to utilize tryptophan for NAD biosynthesis [Lingens64]. Recent studies based on comparative genome analysis have identified the five genes involved in the "eukaryotic" pathway in several bacterial strains, confirming that some bacteria may indeed utilize this pathway rather than the aspartate pathway [Kurnasov03]. In yeast, the de novo pathway consists of six enzymatic steps (catalyzed by the products of the BNA genes) and one non-enzymatic reaction. After the last enzymatic reaction (catalyzed by Bna6p), the de novo pathway converges with the salvage pathway [Panozzo02]. In plants: In plants current evidence strongly supports the NAD biosynthetic route from L-aspartate (NAD biosynthesis I (from aspartate)). However, the finding of gene homologs encoding enzymes of the early steps in the kynurenine pathway (this pathway) in the genome sequence of rice (Oryza sativa) does not rule out this pathway in monocotyledones and remains to be further investigated [Katoh06] [Katoh04].

通常而言，大多数原核生物采用天冬氨酸从头合成途径，其中烟酸基团从天冬氨酸（参见烟酰胺酸（烟酸）的生物合成I（从天冬氨酸））合成。在真核生物中，从头合成途径以色氨酸为起点（本途径）。色氨酸作为真核生物烟酰胺酸生物合成前体的作用，最初由营养学研究提出，其中，患糙皮病（烟酰胺酸（烟酸）缺乏症）的人类在接受膳食中添加色氨酸或烟酸后恢复健康[克雷尔45]。其他研究确定了色氨酸作为许多动物和植物系统中烟酰胺酸的前体[Foster80a]。此途径与色氨酸的分解代谢途径（色氨酸降解I（通过吲哚-3-甲酸））密切相关，暗示了两者之间的进化联系。尽管罕见，但在一些原核生物中已经观察到从色氨酸合成烟酰胺的现象。威尔逊和亨德森报告称，黄单胞菌属的Xanthomonas arboricola pv. pruni需要烟酰胺以促进生长，并可以使用色氨酸或3-羟基吲哚-3-甲酸作为替代物[威尔逊63]。据报道，放线菌属的一些成员也利用色氨酸进行烟酰胺酸生物合成[Lingens64]。基于比较基因组分析的最新研究已识别出在几种细菌菌株中涉及“真核生物”途径的五个基因，证实某些细菌确实可能利用此途径而非天冬氨酸途径[Kurnasov03]。在酵母中，从头合成途径由六个酶促步骤（由BNA基因产物催化）和一个非酶促反应组成。在最后一个酶促反应（由Bna6p催化）之后，从头合成途径与回收途径会合[Panozzo02]。在植物中：当前证据强烈支持从L-天冬氨酸（烟酰胺酸生物合成I（从天冬氨酸））的烟酰胺酸生物合成途径。然而，在水稻（Oryza sativa）基因组序列中发现的编码早期步骤中色氨酸途径（本途径）的酶基因同源物并不排除单子叶植物中此途径的存在，且需要进一步研究[Katoh06][Katoh04]。