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 (Krehl et al). Other studies established tryptophan as a precursor of NAD in many animal and plant systems (Foster et al). 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 (Lingens et al). 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 (Kurnasov et al). 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 (Panozzo et al). 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 (Katoh et al). Adapted from [http://biocyc.org/META/new-image?type=PATHWAY&object=NADSYN-PWY&detail-level=3&ENZORG=TAX-9606 BioCyc].

通常而言，大多数原核生物采用天冬氨酸从头合成途径，其中烟酰胺部分从天冬氨酸（参见烟酰胺的生物合成I（源自天冬氨酸））合成。在真核生物中，从头合成途径以色氨酸为起始（本途径）。色氨酸作为真核生物烟酰胺生物合成前体的作用，最早由营养学研究提出，其中，人类因糙皮病（烟酰胺缺乏病）而受到影响的个体，在饮食中添加色氨酸或烟酸后得以康复（Krehl等）。其他研究确立了色氨酸在众多动物和植物系统中作为烟酰胺前体的地位（Foster等）。此途径与色氨酸分解代谢途径（色氨酸降解I（通过邻氨基苯甲酸））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观察到从色氨酸合成烟酰胺的现象。Wilson和Henderson报告称，黄单胞菌属中的Xanthomonas arboricola pv. pruni需要烟酸以促进生长，并能利用色氨酸或3-羟基邻氨基苯甲酸作为替代品[Wilson63]。据报道，放线菌属的一些成员也利用色氨酸进行烟酰胺的生物合成（Lingens等）。基于比较基因组分析的最新研究已确定在数种细菌菌株中涉及“真核生物”途径的五个基因，证实某些细菌可能确实利用此途径而非天冬氨酸途径（Kurnasov等）。在酵母中，从头合成途径包括六个酶促步骤（由BNA基因产物催化）和一个非酶促反应。在最后的酶促反应（由Bna6p催化）之后，从头合成途径与回收途径（Panozzo等）相汇合。在植物中：目前关于植物NAD生物合成的证据强烈支持从L-天冬氨酸的途径（烟酰胺生物合成I（源自天冬氨酸））。然而，在水稻（Oryza sativa）基因组序列中发现编码犬尿氨酸途径早期步骤酶的基因同源物，并不排除在单子叶植物中存在此途径的可能性，这一发现仍需进一步研究（Katoh等）。资料来源：[http://biocyc.org/META/new-image?type=PATHWAY&object=NADSYN-PWY&detail-level=3&ENZORG=TAX-9606 BioCyc]。