Editing Neisseria gonorrhoeae (section)

=== Carbon ===
Unlike other ''Neisseria'' species that can also metabolize maltose, ''N. gonorrhoeae'' is capable of using only glucose, pyruvate, and lactate as central carbon sources, and glucose is catabolized via both the [[Entner–Doudoroff pathway|Entner-Doudoroff]] (ED) and [[Pentose phosphate pathway|pentose phosphate]] (PP) pathways,and the ED pathway is the primary oxidative method.<ref name="Green_2022" /><ref name="Morse_1980">{{cite book | vauthors = Morse SA, Cacciapuoti AF, Lysko PG | title = Advances in Microbial Physiology Volume 20 | chapter = Physiology of Neisseria gonorrhoeae | volume = 20 | pages = 251–320 | date = 1980-01-01 | pmid = 43667 | doi = 10.1016/s0065-2911(08)60209-x | publisher = Academic Press | isbn = 978-0-12-027720-9 | veditors = Rose AH, Morris JG}}</ref> Use of these pathways is necessary as ''N. gonorrhoeae'' is incapable of glucose catabolism via the [[Embden-Meyerhof-Parnas pathway|Embden-Meyerhof-Parnas]] (EMP) pathway due its lack of the phosphofructokinase (PFK) gene; however, the fructose 1,6-bisphosphatase enzyme is present to allow for [[gluconeogenesis]] to occur.<ref name="Green_2022" />

Glucose is first metabolized through the ED pathway to produce pyruvate and glyceraldehyde 3-phosphate, the latter of which can then further metabolized by enzymes of the EMP pathway to yield another molecule of pyruvate.<ref name="Morse_1974">{{cite journal | vauthors = Morse SA, Stein S, Hines J | title = Glucose metabolism in Neisseria gonorrhoeae | journal = Journal of Bacteriology | volume = 120 | issue = 2 | pages = 702–714 | date = November 1974 | pmid = 4156358 | pmc = 245830 | doi = 10.1128/jb.120.2.702-714.1974 }}</ref> The resultant pyruvate molecules are then converted into [[acetyl-CoA]], which can then be incorporated as a substrate for the [[citric acid cycle]] (CAC) to yield high-energy electron carriers that will be used by the [[electron transport chain]] (ETC) for ATP production; however,  the CAC is largely used for generating biosynthetic precursors rather than for catabolic purposes.<ref name="Green_2022" /><ref name="Hebeler_1976">{{cite journal | vauthors = Hebeler BH, Morse SA | title = Physiology and metabolism of pathogenic neisseria: tricarboxylic acid cycle activity in Neisseria gonorrhoeae | journal = Journal of Bacteriology | volume = 128 | issue = 1 | pages = 192–201 | date = October 1976 | pmid = 824268 | pmc = 232843 | doi = 10.1128/jb.128.1.192-201.1976 }}</ref> This is due in part to inhibited expression of several CAC enzymes in the presence of glucose, pyruvate, or lactate. These enzymes, namely [[citrate synthase]], [[aconitase]], and [[isocitrate dehydrogenase]], are needed for the incorporation of acetate. Instead, a partial CAC has been observed, where α-ketoglutarate is formed by [[glutamate dehydrogenase]] or transamination of oxaloacetate and glutamate by [[Aspartate transaminase|aspartate aminotransferase]] (yielding aspartate and α-ketoglutarate).<ref name="Morse_1980" /><ref name="Hebeler_1976" /> The CAC then continues from there to yield oxaloacetate, which is an important precursor molecule for a number of biosynthetic pathways.<ref name="Hebeler_1976" /> Another differentiating aspect of the gonococcal CAC is the lack of malate dehydrogenase, which is instead replaced by a membrane-bound malate:quinone-oxidoreductase that operates independently of NAD<sup>+</sup> by directly transferring electrons to ubiquinone.<ref name="Green_2022" />

Conversely, acetyl-CoA that does not enter the CAC but enters the [[Phosphate acetyltransferase|phosphotransacetylase]]-[[acetate kinase]] (PTA-AckA) pathway, where it can be converted into acetate by phosphorylation (to form acetyl phosphate and release coenzyme A) and dephosphorylation to form ATP.<ref>{{cite journal | vauthors = Ingram-Smith C, Martin SR, Smith KS | title = Acetate kinase: not just a bacterial enzyme | journal = Trends in Microbiology | volume = 14 | issue = 6 | pages = 249–253 | date = June 2006 | pmid = 16678422 | doi = 10.1016/j.tim.2006.04.001 }}</ref> While this acetate can enter the CAC for further oxidation, this does not occur so long as other carbon sources such as glucose or lactate are present, in which case it is excreted from the cell or incorporated for lipid synthesis.<ref name="Morse_1974" /><ref>{{cite journal | vauthors = Leighton MP, Kelly DJ, Williamson MP, Shaw JG | title = An NMR and enzyme study of the carbon metabolism of Neisseria meningitidis | journal = Microbiology | volume = 147 | issue = Pt 6 | pages = 1473–1482 | date = June 2001 | pmid = 11390678 | doi = 10.1099/00221287-147-6-1473 | doi-access = free }}</ref> ''N. gonorrhoeae'' lack the [[Glyoxylate cycle|glyoxylate shunt]], preventing them from using acetate to form CAC intermediates to replenish the cycle.<ref name="Morse_1974" /><ref name="Morse_1980" />

A significant portion of the glyceraldehyde 3-phosphate formed in gonococci is recycled via the gluconeogenic pathway to reform glucose 6-phosphate, as well as the intermediate fructose 6-phosphate. Both of these can then be used for pentose synthesis in the PP pathway via the oxidative and non-oxidative pathways, respectively, for subsequent nucleotide formation as well as energy production.<ref name="Morse_1980" />

''N. gonorrhoeae'', like other pathogenic members of the genus ''Neisseria'', are  [[capnophile]]s, meaning they require higher-than-normal concentrations of carbon dioxide (CO<sub>2</sub>) to grow , either in the form of CO<sub>2</sub> or bicarbonate (HCO<sub>3</sub><sup>−</sup>) depending on the bacterial strain. This requirement must be met exogenously during the lag and stationary growth phases, though it appears to be met through high metabolic CO<sub>2</sub> productions in the exponential phase. Assimilation of this CO<sub>2</sub> in ''Neisseria'' species is done by [[carbonic anhydrase]] and phosphoenolpyruvate enzymes in the periplasmic space and the cytoplasm, respectively.<ref name="Morse_1980" />

Lactate catabolism is also of particular importance for gonococci, both for pathogenicity and for growth.<ref name="Green_2022" /> External lactate is transported in to the cell via lactate permease (LctP).<ref name="Green_2022" /> The ''N. gonorrhoeae'' genome encodes for three [[lactate dehydrogenase]] (LDH) enzymes for that allow for metabolism of both ''L''-lactate and ''D''-lactate: a cytoplasmic [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]]-dependent ''D''-lactate dehydrogenase (LdhA), which is responsible for and two membrane-bound LDHs, one specific to ''L''-lactate (LldD) and the other specific to ''D''-lactate (LdhD).<ref name="Green_2022" /><ref name="Atack_2014">{{cite journal | vauthors = Atack JM, Ibranovic I, Ong CL, Djoko KY, Chen NH, Vanden Hoven R, Jennings MP, Edwards JL, McEwan AG | title = A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells | journal = The Journal of Infectious Diseases | volume = 210 | issue = 8 | pages = 1311–1318 | date = October 2014 | pmid = 24737798 | pmc = 4215069 | doi = 10.1093/infdis/jiu230 }}</ref> The membrane-bound LDHs have been determined to be [[flavoprotein]]-containing respiratory enzymes that directly oxidize lactate to reduce [[Coenzyme Q10|ubiquinone]]. While these enzymes do not directly pump protons (H<sup>+</sup> ions) into the periplasmic space, it is proposed that the reduction of ubiquinone by these enzymes is capable of feeding into the larger ETC.<ref name="Atack_2014" />