Heme Degradation / Bilirubin Synthesis
Heme Proteins

Marta Lepora - Sara Rossi

CO as vasodilator

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

• For experimental details, see text.
  $ nmole bilirubin formed per min per 10 mg protein A:SD.
  
  Serum Bilirubin