Editing Bilirubin (section)

== Metabolism ==
[[File:Heme Breakdown.png|thumb|upright=1.15|left|Heme metabolism]]
[[File:Bilirubin metabolism diagram.png|thumb|502x502px|Heme and bilirubin metabolism]]
Bilirubin in plasma is mostly produced by the destruction of [[erythrocytes]]. Heme is metabolized into [[biliverdin]] (via heme oxygenase) and then into bilirubin (via [[biliverdin reductase]]) inside the macrophages.<ref name=":3">{{Citation |title=Chapter 7 - Biliary Tract Pathophysiology |date=2007-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9781416032564500156 |work=Surgery of the Liver, Biliary Tract and Pancreas (Fourth Edition) |pages=79–97 |editor-last=Blumgart |editor-first=Leslie H. |access-date=2023-10-31 |place=Philadelphia |publisher=W.B. Saunders |doi=10.1016/B978-1-4160-3256-4.50015-6 |isbn=978-1-4160-3256-4 |editor2-last=Belghiti |editor2-first=Jacques |editor3-last=Jarnagin |editor3-first=William R. |editor4-last=DeMatteo |editor4-first=Ronald P.}}</ref>

Bilirubin is then released into the plasma and transported to the liver bound by [[albumin]], since it is insoluble in water in this state. In this state, bilirubin is called unconjugated (despite being bound by albumin). <ref name=":3" />

In the liver, unconjugated bilirubin is up-taken by the hepatocytes and subsequently conjugated with glucuronic acid (via the enzyme [[Uridine diphosphate glucuronyltransferase|uridine diphosphate–glucuronyl transferase]]). In this state, bilirubin is soluble in water and it is called conjugated bilirubin. <ref name=":3" />

Conjugated bilirubin is excreted into the bile ducts and enters the duodenum. During its transport to the colon, it is converted into [[urobilinogen]] by the bacterial enzyme bilirubin reductase.<ref name=":6">{{Cite journal |last1=Hall |first1=Brantley |last2=Levy |first2=Sophia |last3=Dufault-Thompson |first3=Keith |last4=Arp |first4=Gabriela |last5=Zhong |first5=Aoshu |last6=Ndjite |first6=Glory Minabou |last7=Weiss |first7=Ashley |last8=Braccia |first8=Domenick |last9=Jenkins |first9=Conor |last10=Grant |first10=Maggie R. |last11=Abeysinghe |first11=Stephenie |last12=Yang |first12=Yiyan |last13=Jermain |first13=Madison D. |last14=Wu |first14=Chih Hao |last15=Ma |first15=Bing |date=2024-01-03 |title=BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen |journal=Nature Microbiology |language=en |volume=9 |issue=1 |pages=173–184 |doi=10.1038/s41564-023-01549-x |issn=2058-5276 |pmc=10769871 |pmid=38172624 |doi-access=free}}</ref> Most of the urobilinogen is further reduced into [[stercobilinogen]] and is excreted through feces (air oxidizes stercobilinogen to [[stercobilin]], which gives feces their characteristic brown color). <ref name=":3" />

A lesser amount of urobilinogen is re-absorbed into portal circulation and transferred to the liver. For the most part, this urobilinogen is recycled to conjugated bilirubin and this process closes the enterohepatic circle. There is also an amount of urobilinogen which is not recycled, but rather enters the systemic circulation and subsequently the kidneys, where it is excreted. Air oxidizes urobilinogen into [[urobilin]], which gives urine its characteristic color.<ref name=":3" /><ref name=":4">{{Citation |last=Greenberg |first=Arthur |title=4 - Urinalysis and Urine Microscopy |date=2018-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780323477949000044 |work=National Kidney Foundation' s Primer on Kidney Diseases (Seventh Edition) |pages=33–41 |editor-last=Gilbert |editor-first=Scott J. |access-date=2023-10-31 |place=Philadelphia |publisher=Elsevier |isbn=978-0-323-47794-9 |editor2-last=Weiner |editor2-first=Daniel E.}}</ref>

In parallel, a small amount of conjugated billirubin can also enter the systemic circulation and get excreted through urine. This is exaggerated in various pathological situations.<ref name=":4" />