Editing Histidine (section)

=== Biosynthesis ===
[[File:WP514 85639.svg|thumb|775x775px|'''Histidine Biosynthesis Pathway'''
Eight different enzymes can catalyze ten reactions. In this image, His4 catalyzes four different reactions in the pathway. 
]]
{{sm|l}}-Histidine is an essential amino acid that is not synthesized ''[[De novo synthesis|de novo]]'' in humans.<ref>{{cite journal |last1=Moro |first1=Joanna |last2=Tomé |first2=Daniel |last3=Schmidely |first3=Philippe |last4=Demersay |first4=Tristan-Chalvon |last5=Azzout-Marniche |first5=Dalila |title=Histidine: A Systematic Review on Metabolism and Physiological Effects in Human and Different Animal Species |journal=Nutrients |date=14 May 2020 |volume=12 |issue=5 |pages=1414 |doi=10.3390/nu12051414 |doi-access=free|pmid=32423010 |pmc=7284872 }}</ref> Humans and other animals must ingest histidine or histidine-containing proteins. The biosynthesis of histidine has been widely studied in prokaryotes such as ''E. coli''. Histidine synthesis in ''E. coli'' involves eight gene products (His1, 2, 3, 4, 5, 6, 7, and 8) and it occurs in ten steps. This is possible because a single gene product has the ability to catalyze more than one reaction. For example, as shown in the pathway, [[Histidinol dehydrogenase|His4]] catalyzes 4 different steps in the pathway.<ref name="Alifano1996">{{Cite journal|last1=Alifano|first1=P|last2=Fani|first2=R|last3=Liò|first3=P|last4=Lazcano|first4=A|last5=Bazzicalupo|first5=M|last6=Carlomagno|first6=M S|last7=Bruni|first7=C B|date=1996-03-01|title=Histidine biosynthetic pathway and genes: structure, regulation, and evolution.|journal=Microbiological Reviews|volume=60|issue=1|pages=44–69|issn=0146-0749|pmc=239417|pmid=8852895|doi=10.1128/MMBR.60.1.44-69.1996}}</ref>

Histidine is synthesized from [[phosphoribosyl pyrophosphate]] (PRPP), which is made from [[ribose-5-phosphate]] by [[ribose-phosphate diphosphokinase]] in the [[pentose phosphate pathway]]. The first reaction of histidine biosynthesis is the condensation of PRPP and [[adenosine triphosphate]] (ATP) by the enzyme [[ATP phosphoribosyltransferase|ATP-phosphoribosyl transferase]]. ATP-phosphoribosyl transferase is indicated by His1 in the image.<ref name="Alifano1996" /> His4 gene product then hydrolyzes the product of the condensation, phosphoribosyl-ATP, producing phosphoribosyl-AMP (PRAMP), which is an irreversible step. His4 then catalyzes the formation of phosphoribosylformiminoAICAR-phosphate, which is then converted to phosphoribulosylformimino-AICAR-P by the His6 gene product.<ref name="Kulis-Horn2014">{{Cite journal|last1=Kulis-Horn|first1=Robert K|last2=Persicke|first2=Marcus|last3=Kalinowski|first3=Jörn|date=2014-01-01|title=Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum|journal=Microbial Biotechnology|volume=7|issue=1|pages=5–25|doi=10.1111/1751-7915.12055|issn=1751-7915|pmc=3896937|pmid=23617600}}</ref> His7 splits phosphoribulosylformimino-AICAR-P to form {{sm|d}}-erythro-imidazole-glycerol-phosphate. After, His3 forms imidazole acetol-phosphate releasing water. His5 then makes {{sm|l}}-histidinol-phosphate, which is then hydrolyzed by His2 making [[histidinol]]. [[Histidinol dehydrogenase|His4]] catalyzes the oxidation of {{sm|l}}-histidinol to form {{sm|l}}-histidinal, an amino aldehyde. In the last step, {{sm|l}}-histidinal is converted to {{sm|l}}-histidine.<ref name="Kulis-Horn2014" /><ref>{{Cite journal|last=Adams|first=E.|date=1955-11-01|title=L-Histidinal, a biosynthetic precursor of histidine|journal=The Journal of Biological Chemistry|volume=217|issue=1|pages=325–344|doi=10.1016/S0021-9258(19)57184-8|issn=0021-9258|pmid=13271397|doi-access=free}}</ref>

The histidine biosynthesis pathway has been studied in the fungus ''[[Neurospora crassa]]'', and a gene (''His-3'') encoding a [[multienzyme complex]] was found that was similar to the ''His4'' gene of the bacterium ''[[Escherichia coli|E. coli]]''.<ref name="Ahmed1968">Ahmed A. Organization of the histidine-3 region of Neurospora. Mol Gen Genet. 1968;103(2):185-93. doi: 10.1007/BF00427145. PMID 4306011</ref> A genetic study of ''N. crassa'' histidine [[mutant]]s indicated that the individual activities of the multienzyme complex occur in discrete, contiguous sections of the ''His-3'' [[gene mapping|genetic map]], suggesting that the different activities of the multienzyme complex are encoded separately from each other.<ref name = Ahmed1968/> However, mutants were also found that lacked all three activities simultaneously, suggesting that some mutations cause loss of function of the complex as a whole.

Just like animals and microorganisms, plants need histidine for their growth and development.<ref name="Ingle2011" /> Microorganisms and plants are similar in that they can synthesize histidine.<ref>{{cite web |last=DeNofrio |first=Jan |url=https://www.thetech.org/ask-a-geneticist/articles/2011/ask396/ |title=How come plants can make essential amino acids but people can't? |website=[[The Tech Interactive]] |series=Ask a Geneticist |date=2011-02-08 |access-date=2024-08-04}}</ref> Both synthesize histidine from the biochemical intermediate phosphoribosyl pyrophosphate. In general, the histidine biosynthesis is very similar in plants and microorganisms.<ref>{{Cite journal|last1=Stepansky|first1=A.|last2=Leustek|first2=T.|date=2006-03-01|title=Histidine biosynthesis in plants|journal=Amino Acids|volume=30|issue=2|pages=127–142|doi=10.1007/s00726-005-0247-0|issn=0939-4451|pmid=16547652|s2cid=23733445}}</ref>

==== Regulation of biosynthesis ====
This pathway requires energy in order to occur therefore, the presence of ATP activates the first enzyme of the pathway, ATP-phosphoribosyl transferase (shown as His1 in the image on the right). ATP-phosphoribosyl transferase is the rate determining enzyme, which is regulated through feedback inhibition meaning that it is inhibited in the presence of the product, histidine.<ref>{{Cite journal|last1=Cheng|first1=Yongsong|last2=Zhou|first2=Yunjiao|last3=Yang|first3=Lei|last4=Zhang|first4=Chenglin|last5=Xu|first5=Qingyang|last6=Xie|first6=Xixian|last7=Chen|first7=Ning|date=2013-05-01|title=Modification of histidine biosynthesis pathway genes and the impact on production of L-histidine in ''Corynebacterium glutamicum''|journal=Biotechnology Letters|volume=35|issue=5|pages=735–741|doi=10.1007/s10529-013-1138-1|issn=1573-6776|pmid=23355034|s2cid=18380727}}</ref>