Page 203 - Color Atlas of Biochemistry

194 Metabolism

Heme degradation Some of the bilirubin conjugates are bro-
kendownfurther in the intestine by bacterial
b-glucuronidases. The bilirubin released is
A. Degradation of heme groups
then reduced further via intermediate steps
Heme is mainly found in the human organism into colorless stercobilinogen,some of which
as a prosthetic group in erythrocyte hemoglo- is oxidized again into orange to yellow-col-
bin. Around 100–200 million aged erythro- ored stercobilin. The end products of bile pig-
cytes per hour are brokendown inthe human ment metabolism in the intestine are mostly
organism. The degradation process starts in excreted in feces, but a small proportion is
reticuloendothelial cells in the spleen, liver, resorbed (enterohepatic circulation; see
and bone marrow. p. 314). Whenhighlevels ofheme degrada-
[1] After the protein part (globin) has been tion are taking place, stercobilinogen appears
removed, thetetrapyrroleringof hemeis as urobilinogen in the urine, where oxidative
oxidatively cleaved between rings A and B processes darken it to form urobilin.
by heme oxygenase. This reaction requires In addition to hemoglobin, other heme pro-
+
molecular oxygen and NADPH+H ,and pro- teins (myoglobin, cytochromes, catalases, and
duces green biliverdin, aswell asCO(carbon peroxidases; see p. 32) also supply heme
2+
monoxide) and Fe , which remains available groups that are degraded via the same path-
for further use (see p. 286). way. However, these contribute only about
[2] In another redox reaction, biliverdin is 10–15% to a total of ca. 250 mg of bile pig-
reduced by biliverdin reductase to the orange- ment formed per day.
colored bilirubin. The color change from pur-
ple to green to yellow can be easily observed
in vivo in a bruise or hematoma. Further information
The color of heme and the other porphyrin Hyperbilirubinemias. An elevated bilirubin
–1
systems (see p. 106) results from their numer- level (> 10 mg L )is known as hyperbiliru-
ous conjugated double bonds. Heme contains binemia. When this is present, bilirubin dif-
a cyclic conjugation (highlighted in pink) that fuses from the blood into peripheral tissue
is removed by reaction [1]. Reaction [2] and gives it a yellow color (jaundice). The
breaks the π system down into two smaller easiest way of observing this is in the white
separate systems (highlighted in yellow). conjunctiva of the eyes.
For further degradation, bilirubin is trans- Jaundice can have various causes. If in-
ported to the liver via the blood. As bilirubin is creased erythrocyte degradation (hemolysis)
poorly soluble, it is bound to albumin for produces more bilirubin, it causes hemolytic
transport. Some drugs that alsobind toalbu- jaundice. If bilirubin conjugation in the liver is
min can lead to an increase in free bilirubin. impaired—e. g., due to hepatitis or liver cir-
[3] The hepatocytes take up bilirubin from rhosis—it leads to hepatocellular jaundice,
the blood and conjugate it in the endoplasmic which is associated with an increase in un-
reticulum with the help of UDP-glucuronic conjugated (“indirect”) bilirubin in the blood.
acid into themoreeasilysoluble bilirubin By contrast, if there is a disturbance of bile
monoglucuronides and diglucuronides.To do drainage (obstructive jaundice, due to gall-
this, UDP-glucuronosyltransferase forms ester- stones or pancreatic tumors), then conjugated
type bonds between the OH group at C-1 of (“direct”) bilirubin in the blood increases. Neo-
glucuronic acid and the carboxyl groups in natal jaundice (physiologic jaundice) usually
bilirubin (see p. 316). The glucuronides are resolves after a few days by itself. In severe
then excreted by active transport into the cases, however, unconjugated bilirubin can
bile, where they form what are known as cross the blood–brain barrier and lead to
the bile pigments. brain damage (kernicterus).
Glucuronide synthesis is the rate-deter-
mining step in hepatic bilirubin metabolism.
Drugs such as phenobarbital, for example, can
induce both conjugate formation and the
transport process.

Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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