Stercobilin

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Stercobilin
Stercobilin.png
Names
IUPAC name
3-[(2E)-2-[[3-(2-Carboxyethyl)-5-[(4-ethyl-3-methyl-5-oxo-pyrrolidin-2-yl)methyl]-4-methyl-1H-pyrrol-2-yl]methylidene]-5-[(3-ethyl-4-methyl-5-oxo-pyrrolidin-2-yl) methyl]-4-methyl-pyrrol-3-yl]propanoic acid
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.047.155 OOjs UI icon edit-ltr-progressive.svg
MeSH Stercobilin
PubChem CID
UNII
  • InChI=1S/C33H46N4O6/c1-7-20-19(6)32(42)37-27(20)14-25-18(5)23(10-12-31(40)41)29(35-25)15-28-22(9-11-30(38)39)17(4)24(34-28)13-26-16(3)21(8-2)33(43)36-26/h15-16,19-21,26-27,35H,7-14H2,1-6H3,(H,36,43)(H,37,42)(H,38,39)(H,40,41)/b28-15-/t16-,19-,20-,21-,26+,27+/m1/s1 X mark.svgN
    Key: DEEUSUJLZQQESV-BQUSTMGCSA-N X mark.svgN
  • CC[C@@H]1[C@H](C(=O)N[C@H]1Cc2c(c(c([nH]2)/C=C\3/C(=C(C(=N3)C[C@H]4[C@@H]([C@H](C(=O)N4)CC)C)C)CCC(=O)O)CCC(=O)O)C)C
Properties
C33H46N4O6
Molar mass 594.742
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Stercobilin is a tetrapyrrolic bile pigment and is one end-product of heme catabolism. [1] [2] It is the chemical responsible for the brown color of human feces and was originally isolated from feces in 1932. Stercobilin (and related urobilin) can be used as a marker for biochemical identification of fecal pollution levels in rivers. [3]

Metabolism

Stercobilin results from breakdown of the heme moiety of hemoglobin found in erythrocytes (red blood cells). Macrophages break down senescent erythrocytes and break the heme down into biliverdin, which rapidly reduces to free bilirubin. Bilirubin binds tightly to plasma proteins (especially albumin) in the blood stream and is transported to the liver, where it is conjugated with one or two glucuronic acid residues into bilirubin diglucuronide, and secreted into the small intestine as bile. In the small intestine, some bilirubin glucuronide is converted back to bilirubin via bacterial enzymes in the terminal ileum. This bilirubin is further converted to colorless urobilinogen by the bacterial enzyme bilirubin reductase. [4] Urobilinogen that remains in the colon can either be reduced to stercobilinogen and finally oxidized to stercobilin, or it can be directly reduced to stercobilin. Stercobilin is responsible for the brown color of human feces. Stercobilin is then excreted in the feces. [5]

Role in disease

Obstructive jaundice

In obstructive jaundice, no bilirubin reaches the small intestine, meaning that there is no formation of stercobilinogen. The lack of stercobilin and other bile pigments causes feces to become clay-colored. [5]

Brown pigment gallstones

An analysis of two infants suffering from cholelithiasis observed that a substantial amount of stercobilin was present in brown pigment gallstones. This study suggested that brown pigment gallstones could form spontaneously in infants suffering from bacterial infections of the biliary tract. [6]

Role in treatment of disease

A 1996 study by McPhee et al. suggested that stercobilin and other related pyrrolic pigments — including urobilin, biliverdin, and xanthobilirubic acid — has potential to function as a new class of HIV-1 protease inhibitors when delivered at low micromolar concentrations. These pigments were selected due to a similarity in shape to the successful HIV-1 protease inhibitor Merck L-700,417 (N,N-bis(2-hydroxy-1-indanyl)-2,6-diphenylmethyl-4-hydroxy-1,7-heptandiamide). Further research is suggested to study the pharmacological efficacy of these pigments. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Jaundice</span> Abnormal pigmentation symptom for disease of the liver

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.

<span class="mw-page-title-main">Bilirubin</span> Red pigment of the bile

Bilirubin (BR) is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the destruction of aged or abnormal red blood cells. In the first step of bilirubin synthesis, the heme molecule is stripped from the hemoglobin molecule. Heme then passes through various processes of porphyrin catabolism, which varies according to the region of the body in which the breakdown occurs. For example, the molecules excreted in the urine differ from those in the feces. The production of biliverdin from heme is the first major step in the catabolic pathway, after which the enzyme biliverdin reductase performs the second step, producing bilirubin from biliverdin.

<span class="mw-page-title-main">Bile</span> Dark greenish-brown fluid aiding in the digestion of fats

Bile, or gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, produced continuously by the liver, and stored and concentrated in the gallbladder. After a human eats, this stored bile is discharged into the first section of the small intestine.

<span class="mw-page-title-main">Heme</span> Chemical coordination complex of an iron ion chelated to a porphyrin

Heme, or haem, is a ring-shaped iron-containing molecular component of hemoglobin, which is necessary to bind oxygen in the bloodstream. It is composed of four pyrrole rings with 2 vinyl and 2 propionic acid side chains. Heme is biosynthesized in both the bone marrow and the liver.

<span class="mw-page-title-main">Erythropoietic protoporphyria</span> Medical condition

Erythropoietic protoporphyria is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells (erythrocytes), plasma, skin, and liver. The severity varies significantly from individual to individual.

<span class="mw-page-title-main">Biliverdin</span> Green bile pigment

Biliverdin is a green tetrapyrrolic bile pigment, and is a product of heme catabolism. It is the pigment responsible for a greenish color sometimes seen in bruises.

<span class="mw-page-title-main">Enterohepatic circulation</span> Circulation of substances in the human digestive system

Enterohepatic circulation is the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepatic circulation is an especially important concept in the field of toxicology as many lipophilic xenobiotics undergo this process causing repeated liver damage.

<span class="mw-page-title-main">Neonatal jaundice</span> Medical condition

Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral palsy, or kernicterus.

<span class="mw-page-title-main">Bile acid</span> Steroid acid found predominantly in the bile of mammals and other vertebrates

Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.

<span class="mw-page-title-main">Urobilinogen</span> Chemical compound

Urobilinogen is a yellow by-product of bilirubin reduction. It is formed in the intestines by the bacterial enzyme bilirubin reductase. About half of the urobilinogen formed is reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidney.

<span class="mw-page-title-main">Heme oxygenase</span> Class of enzymes

Heme oxygenase, or haem oxygenase, is an enzyme that catalyzes the degradation of heme to produce biliverdin, ferrous iron, and carbon monoxide.

<span class="mw-page-title-main">Biliverdin reductase</span> Class of enzymes

Biliverdin reductase (BVR) is an enzyme found in all tissues under normal conditions, but especially in reticulo-macrophages of the liver and spleen. BVR facilitates the conversion of biliverdin to bilirubin via the reduction of a double bond between the second and third pyrrole ring into a single bond.

<span class="mw-page-title-main">Urobilin</span> Yellow pigment in urine

Urobilin or urochrome is the chemical primarily responsible for the yellow color of urine. It is a linear tetrapyrrole compound that, along with the related colorless compound urobilinogen, are degradation products of the cyclic tetrapyrrole heme.

<span class="mw-page-title-main">Bilin (biochemistry)</span> Class of chemical compound

Bilins, bilanes or bile pigments are biological pigments formed in many organisms as a metabolic product of certain porphyrins. Bilin was named as a bile pigment of mammals, but can also be found in lower vertebrates, invertebrates, as well as red algae, green plants and cyanobacteria. Bilins can range in color from red, orange, yellow or brown to blue or green.

<span class="mw-page-title-main">Stercobilinogen</span> Chemical compound

Stercobilinogen is a chemical created by bacteria in the gut. It is made of broken-down hemoglobin. It is further processed to become the chemical that gives feces its brown color.

<span class="mw-page-title-main">Bilirubinuria</span> Medical condition

In medicine, bilirubinuria is an abnormality in which conjugated bilirubin is detected in the urine.

<span class="mw-page-title-main">Human feces</span> Metabolic waste of the human digestive system

Human feces or faeces, commonly and in medical literature more often called stool, are the solid or semisolid remains of food that could not be digested or absorbed in the small intestine of humans, but has been further broken down by bacteria in the large intestine. It also contains bacteria and a relatively small amount of metabolic waste products such as bacterially altered bilirubin, and the dead epithelial cells from the lining of the gut. It is discharged through the anus during a process called defecation.

<span class="mw-page-title-main">Urine test strip</span> Diagnostic tool used in urinalysis

A urine test strip or dipstick is a basic diagnostic tool used to determine pathological changes in a patient's urine in standard urinalysis.

Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.

<span class="mw-page-title-main">Tin mesoporphyrin</span> Compound in biochemistry

Tin mesoporphyrin (SnMP), also known as stannsoporfin, is a metalloporphyrin, which inhibits heme oxygenase. It can be used in the treatment of neonatal hyperbilirubinemia.

References

  1. Boron W, Boulpaep E (2005). Medical Physiology: A cellular and molecular approach. United States: Elsevier Saunders. pp. 984–986. ISBN   1-4160-2328-3.
  2. Kay IT, Weimer M, Watson CJ (1963). "The formation in vitro of stercobilin from bilirubin" (PDF). Journal of Biological Chemistry . 238: 1122–1123. PMID   14031566.
  3. Lam CW, Lai CK, Chan YW (February 1998). "Simultaneous fluorescence detection of fecal urobilins and porphyrins by reversed-phase high-performance thin-layer chromatography". Clinical Chemistry. 44 (2): 345–346. doi: 10.1093/clinchem/44.2.345 . PMID   9474036.
  4. Hall B, Levy S, Dufault-Thompson K, Arp G, Zhong A, Ndjite GM, et al. (January 2024). "BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen". Nature Microbiology. 9 (1): 173–184. doi:10.1038/s41564-023-01549-x. PMC   10769871 . PMID   38172624.
  5. 1 2 Seyfried H, Klicpera M, Leithner C, Penner E (August 1976). "[Bilirubin metabolism (author's transl)]". Wiener Klinische Wochenschrift (in German). 88 (15): 477–482. PMID   793184.
  6. Treem WR, Malet PF, Gourley GR, Hyams JS (February 1989). "Bile and stone analysis in two infants with brown pigment gallstones and infected bile". Gastroenterology. 96 (2 Pt 1): 519–523. doi: 10.1016/s0016-5085(89)91579-5 . PMID   2642880.
  7. McPhee F, Caldera PS, Bemis GW, McDonagh AF, Kuntz ID, Craik CS (December 1996). "Bile pigments as HIV-1 protease inhibitors and their effects on HIV-1 viral maturation and infectivity in vitro". The Biochemical Journal. 320 (Pt 2): 681–686. doi: 10.1042/bj3200681 . PMC   1217983 . PMID   8973584.