A heme molecule is a fundamental organic, ring-shaped structure found throughout biological systems. Its unique architecture allows it to host an iron atom, making it a versatile component in numerous life-sustaining processes. Its name, derived from the Greek word for “blood,” reflects its prominent role in red blood cells. Heme is not limited to blood; it is interwoven into the fabric of life, facilitating diverse biochemical reactions across various organisms.
The Building Blocks of Heme
At its core, a heme molecule is a porphyrin, a large heterocyclic organic compound. This porphyrin ring system is formed from four smaller pyrrole subunits, which are five-sided molecules containing four carbon atoms and one nitrogen atom. These pyrrole units are cyclically linked together by methine bridges, creating a planar structure.
Within the center of the porphyrin ring resides a single iron atom, specifically in its ferrous (Fe2+) oxidation state. This iron atom is coordinated with the four nitrogen atoms at the center of the pyrrole rings, allowing it to reversibly bind to other molecules. As a non-protein unit tightly bound to proteins and necessary for their biological function, heme is classified as a prosthetic group.
Heme’s Essential Roles in the Body
Heme’s structure enables it to perform various biological functions, particularly in processes involving gases and electron transfer. A primary function involves oxygen transport and storage, notably within hemoglobin in red blood cells and myoglobin in muscle tissue. Hemoglobin, a protein composed of four subunits, each containing a heme group, binds oxygen in the lungs and delivers it to tissues. Myoglobin, a smaller, single-subunit protein, stores oxygen within muscle cells, releasing it when oxygen demand increases.
Beyond oxygen, heme plays a significant part in the electron transport chain, a series of protein complexes within mitochondria that generate cellular energy. Heme is a component of cytochromes, which are redox-active proteins. The iron atom within the heme group of cytochromes undergoes reversible changes between its ferrous (Fe2+) and ferric (Fe3+) oxidation states, allowing it to accept and donate electrons. This electron transfer drives the pumping of protons across the inner mitochondrial membrane, creating a gradient that powers ATP synthesis.
Heme also acts as a prosthetic group for various enzymes involved in cellular detoxification. Enzymes like catalase and peroxidases, which contain heme, are responsible for breaking down hydrogen peroxide, a potentially harmful reactive oxygen species. Catalase specifically dismutates two molecules of hydrogen peroxide into water and oxygen, preventing its buildup. Peroxidases, on the other hand, use hydrogen peroxide to oxidize a wide range of organic and inorganic substrates, protecting cells from oxidative damage.
How Heme is Made and Broken Down
Heme synthesis is an eight-step enzymatic pathway that occurs partially in the mitochondria and partially in the cytosol of cells. This process begins in the mitochondria with the condensation of succinyl Co-A, derived from the citric acid cycle, and the amino acid glycine. These precursors combine to form delta-aminolevulinic acid (ALA), an intermediate, a reaction catalyzed by the enzyme ALA synthase.
Following several enzymatic conversions in the cytosol, a porphyrin ring structure is gradually assembled. The final steps of heme synthesis occur back in the mitochondria, where protoporphyrin IX is formed. The last reaction involves the insertion of a ferrous iron atom into the center of the protoporphyrin IX ring, a process mediated by the enzyme ferrochelatase, resulting in the completed heme molecule. The major sites for heme synthesis are the bone marrow, primarily for hemoglobin production in red blood cells, and the liver, where it is largely incorporated into cytochrome P450 enzymes.
Heme undergoes a degradation process, primarily in cells of the reticuloendothelial system (e.g., in the spleen). The initial step involves the enzyme heme oxygenase, which opens the porphyrin ring, releasing the iron atom and producing carbon monoxide and a green pigment called biliverdin. Biliverdin is then converted to a yellow pigment, bilirubin, through the action of biliverdin reductase. This bilirubin is transported to the liver, where it is modified to a water-soluble form and ultimately excreted as a component of bile.
When Heme Metabolism Goes Wrong
Disruptions in the pathways of heme synthesis or degradation can lead to various health conditions. A group of metabolic disorders known as porphyrias result from deficiencies in specific enzymes involved in the heme biosynthesis pathway. These enzymatic defects cause a buildup of heme precursors, called porphyrins, which can accumulate in different tissues and lead to a range of symptoms. Depending on which enzyme is deficient and where the precursors accumulate, porphyrias can cause neurovisceral abnormalities or skin sensitivity to light.
Problems with heme degradation can also manifest in visible symptoms. When the breakdown of heme is impaired or its excretion from the body is hindered, bilirubin can accumulate in the bloodstream. This accumulation leads to jaundice, a condition characterized by a yellowish discoloration of the skin and eyes. Jaundice is particularly common in newborns due to their still-developing heme metabolism pathways.