Heme Degradation / Bilirubin Synthesis
Heme Proteins

Author: Gianpiero Pescarmona
Date: 31/12/2009



Heme-oxygenase (HO) is the first step of Heme degradation

Different Isoforms of Heme-oxygenase are active in different cells (HMOX-1, HMOX-2)

HO-1 is inducible by the same factors that induce COX-2 and iNOS

Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion.

Central CO-heme oxygenase pathway raises body temperature by a prostaglandin-independent way.

CO effects

Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism 2003

Involvement of the Heme Oxygenase–Carbon Monoxide Pathway in Keratinocyte Proliferation

Biliverdin and more

Albumin: a multi-purpose carrier

Genetic Hyperbilirubinemia

Gibert syndrome


Choleretic Effect of licorice

Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration, 2016

Compared to their normobilirubinemic siblings, aged hyperbilirubinemic Gunn rats showed significantly smaller amounts of visceral fat, better glucose tolerance, and decreased serum levels of proinflammatory cytokines TNFα, IL-1β, and IL-18. Simultaneously, livers from Gunn rats showed decreased expression of senescence markers and cell cycle inhibitors p21 and p16.


Is associated with Anemia, Diabetes, Osteoporosis, and (Aromatase deficiency?)

Referee_supplementary_info_Diabetes_and_Osteoporosis, 2021

h4 Hyperbilirubinemia

Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses, 2021

In addition to bilirubin’s known role as an antioxidant and anti-inflammatory molecule, it is now recognized that unconjugated bilirubin is also a potent endogenous activator of several ligand-activated transcriptional factors crucially involved in metabolic homeostasis, including peroxisome proliferator-activated receptor alpha (PPAR-α), aryl hydrocarbon receptor, constitutive androsterone receptor (CAR), liver X receptors (LXRs), and pregnane X receptor (PXR) --> induces CYP24 that inactivates 1,25 (OH)2Vit D.

Potential cardiovascular risk protection of bilirubin in end-stage renal disease patients under hemodialysis. 2014

Additionally, a significant positive correlation between bilirubin and serum iron and transferrin saturation and a significant negative correlation between bilirubin and transferrin were found.

2022-03-15T15:57:51 - Gianpiero Pescarmona

UGT1 upregulation


sarà vero?

Sulforaphane suppresses carcinogenesis of colorectal cancer through the ERK/Nrf2‑UDP glucuronosyltransferase 1A metabolic axis activation. 2020

Previous studies revealed that SFN upregulates the expression of UGT1A.


2013-06-28T21:27:22 - Sara Rossi


The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers was significantly correlated with bilirubin O-glucuronosyltransferase (r = 0.855, p < 0.001) and estradiol 3-O-glucuronosyltransferase (r = 0.827, p < 0.0001) activities catalyzed by UGT1A1, indicating that the activity in human liver is mainly catalyzed by UGT1A1.

Marta Lepora - Sara Rossi

CO as vasodilator

2012-02-08T16:51:06 - alessandra pelle

Chianale Valentina

Glucagon and heme - oxydase

A possible mechanism that may be advanced to account for the positive relationship between fasting or hypoglycemia and the rise in serum bilirubin, is enhancement of bilirubin formation from increased heme turnover in the liver. In fact some studies about hepatic HO activity in rats show that HO activity increases progressively, reaching approximately 3 times the control value after 72 hours of fasting.
A study valuates HO activity in relation with some hormones that are enhanced during hypoglycemia and starvation and reduced after meals: glucagon, insulin, epinephrine, arginine (which triggers the release of endogenous glucagon). The results of this study are below.
Glucagon injection doubled the hepatic HO activity, while splenic HO activity remained unaffected (Table II). Glucose given together with glucagon did not abolish the stimulatory effect of the hormone (Table II). In animals whose hepatic HO had been stimulated by 48 hr fasting, glucagon had no additional effect on the enzyme activity (Fig. 2). However, on prolonged starvation, glucagon given at 72 and 92 hr doubled and tripled HO activity as compared to that in untreated rats fasted for the same length of time. Arginine, caused a fivefold increase in hepatic HO activity (Table II). This rise in activity exceeded the enzyme stimulation obtained with individual glucagon injections at 7 and 5, or 5 and 3 hr before assay (Table II). Epinephrine (0.1 mg/100 g rat) and glucagon (1 mg/100 g rat) given together in two i.p. injections 7 and 5 hr before enzyme assay produced additive enhancement of hepatic enzyme activity (Table II)
Insulin-induced hypoglycemia was associated with an increase in hepatic HO activity that was similar to that seen in fasted animals (Table I). This stimulatory effect of insulin was blunted or abolished when the injected insulin was "covered" with glucose administered simultaneously (Table I), which indicates that insulin by itself does not stimulate the enzyme.

link Metabolic Regulation of Heme Catabolism and Bilirubin Production I. HORMONAL CONTROL OF HEPATIC HEME OXYGENASE ACTIVITY.

TABLE I: Hepatic Heme Oxygenase Activity: Effect of Hypoglycemia

Treatment*n°of animalsenzyme activity
Saline60.05 4-0.02
Insulin, 1 IU40.12 :410.02
Insulin, 12 IU40.34 :10.04
Insulin, 12 IU plus glucose40.13 :10.03
Insulin, 1 IU plus glucose50.06 :10.02
Mannose50.33 :4:0.05
  • For experimental details, see text.
    $ nmole bilirubin formed per min per 10 mg protein A:SD.

    Serum Bilirubin
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