Heme is a complex molecule containing iron, a key component of various proteins, most notably hemoglobin in red blood cells. Hemoglobin transports oxygen from the lungs to tissues throughout the body. Heme has a limited lifespan and must be processed and removed from the body in a safe manner. This breakdown process is continuous and essential for health.
Why the Body Breaks Down Heme
The body breaks down heme primarily due to the natural turnover of red blood cells. As these cells age or become damaged, they are removed from circulation, primarily in the spleen, liver, and bone marrow. Hemoglobin within these old red blood cells is then broken down, releasing heme.
Free heme, if not properly managed, can be harmful to cells and tissues. Its iron content can participate in reactions that generate damaging free radicals, leading to cellular damage. The degradation pathway acts as a detoxification system, preventing the accumulation of this toxic molecule. This process also allows for the recycling of iron, a valuable mineral, for use in new hemoglobin synthesis.
The Step-by-Step Breakdown
The degradation of heme begins inside macrophages, specialized immune cells. First, hemoglobin is separated into its two main components: heme and globin. The globin portion, which is protein, is broken down into amino acids that the body can reuse.
The heme molecule then undergoes a series of enzymatic reactions. The first step is catalyzed by the enzyme heme oxygenase (HO). This enzyme breaks open the ring structure of heme, converting it into a linear molecule called biliverdin. During this reaction, carbon monoxide and iron are also released.
Next, biliverdin is further processed by a second enzyme, biliverdin reductase (BVR). This enzyme reduces biliverdin, transforming it into bilirubin. Both heme oxygenase and biliverdin reductase require NADPH for these transformations.
What Happens Next to the Byproducts
The bilirubin produced from heme degradation is initially “unconjugated,” meaning it is not water-soluble. Its insolubility means it cannot travel freely in the bloodstream and must bind to a protein called albumin for transport to the liver.
Upon reaching the liver, the unconjugated bilirubin enters liver cells where it undergoes a process called “conjugation.” Here, an enzyme called UDP-glucuronyl transferase (UGT) attaches glucuronic acid to bilirubin, making it water-soluble. This conjugated bilirubin can then be excreted.
The water-soluble conjugated bilirubin is then actively transported from the liver cells into the bile. Bile, a digestive fluid, carries the bilirubin into the small intestine and then to the large intestine. In the large intestine, gut bacteria deconjugate and further metabolize the bilirubin into colorless compounds called urobilinogens.
Some urobilinogen is reabsorbed into the bloodstream and eventually excreted by the kidneys as urobilin, which gives urine its characteristic yellow color. Most of the urobilinogen, however, remains in the intestines and is converted into stercobilin, a brown pigment responsible for the color of feces.
When the Process Isn’t Smooth
When the heme degradation pathway encounters disruptions, bilirubin can accumulate in the body, leading to jaundice. Jaundice is characterized by the yellowing of the skin and whites of the eyes. This accumulation can occur for several reasons.
One common cause is the excessive breakdown of red blood cells. This leads to an overproduction of unconjugated bilirubin, overwhelming the liver’s capacity to process it. Liver problems, such as disease or damage, can also impair the liver’s ability to conjugate bilirubin, resulting in its buildup. An obstruction in the bile ducts can finally prevent conjugated bilirubin from being excreted into the intestines, causing it to back up into the bloodstream.