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BiliverdinEdit

Biliverdin is a green bile pigment that appears as a transient product in the breakdown of heme, the iron-containing core of hemoproteins such as hemoglobin and myoglobin. It forms when the enzyme system responsible for heme catabolism, notably heme oxygenase, cleaves the heme molecule to yield biliverdin IX alpha (the principal physiologic isomer), alongside iron and carbon monoxide. In humans, biliverdin is typically converted rapidly to bilirubin by biliverdin reductase, and bilirubin is further processed in the liver by UDP-glucuronosyltransferase to bilirubin diglucuronide for excretion into bile. The bilirubin–biliverdin axis is a fundamental part of cellular recycling, and biliverdin itself has roles beyond being a stepping stone to bilirubin.

In nature, biliverdin is the pigment responsible for the greenish coloration that accompanies the breakdown of heme in many species, and it can accumulate in bile and tissues under certain circumstances. Because it is a product of heme metabolism, biliverdin sits at the intersection of respiratory pigments, detoxification pathways, and antioxidant defense. In modern biomedicine, biliverdin has also found a place as a research tool and imaging reagent; it acts as a chromophore for near-infrared fluorescent proteins, enabling deep-tissue imaging and dynamic studies in living organisms. For example, near-infrared fluorescent proteins such as iRFP rely on biliverdin to produce their characteristic glow, highlighting a practical bridge between basic metabolism and clinical research.

Biochemistry and biosynthesis

Pathway

  • Heme is cleaved by heme oxygenase to produce biliverdin IX alpha, free iron, and carbon monoxide. This reaction initiates the catabolic pathway that recycles heme from hemoproteins.
  • Biliverdin is reduced to bilirubin by biliverdin reductase, a step that is distributed across various tissues and cell types.
  • Bilirubin is conjugated in the liver by UDP-glucuronosyltransferase to bilirubin diglucuronide, increasing water solubility for excretion in bile as part of the broader process of bilirubin metabolism.
  • Excretion can occur through bile into the digestive tract; in some species or physiological states, biliverdin or bilirubin can also be processed by the kidney to be eliminated in urine.

Isomers and chemistry

  • The most relevant physiologic form in humans is biliverdin IX alpha (BV IX α). There are isomeric varieties of biliverdin, and structural nuances influence its reactivity and conversion to bilirubin. For readers of porphyrin metabolism, biliverdin represents a green intermediate linked to the photoreactive and redox properties of heme breakdown products.

Imaging and research applications

  • Biliverdin serves as the native chromophore for several near-infrared fluorescent proteins, enabling researchers to image cellular and tissue processes with minimal autofluorescence interference. This imaging utility is part of why biliverdin has become a useful tool in biomedical imaging and related fields, including the development of biliverdin-based probes and reporters.

Biological roles and distribution

In mammals

  • In humans and many mammals, bilirubin is the terminal bile pigment in the heme degradation pathway, but biliverdin is still present transiently during metabolism. Biliverdin and bilirubin have been studied for their potential cytoprotective effects against oxidative stress, with the notion that these pigments can scavenge reactive oxygen species and stabilize cellular redox balance under certain conditions.

In other organisms

  • In birds, reptiles, and some amphibians, biliverdin can be a more prominent pigment in bile or plumage, reflecting species-specific differences in pigment handling and metabolism. The relative abundance of biliverdin versus bilirubin as bile pigments varies across taxa and physiological states, illustrating the evolutionary diversity of heme breakdown.

Health and disease associations

  • Clinically, bilirubin levels are commonly measured as part of liver function tests and newborn screening. While biliverdin itself is less frequently a direct diagnostic target, understanding its relation to bilirubin metabolism helps explain conditions such as neonatal jaundice, cholestasis, and hemolysis. The balance between biliverdin production, biliverdin reductase activity, and bilirubin conjugation underpins the body’s ability to manage heme-derived compounds safely.

Clinical significance and applications

Neonatal jaundice and treatment

  • A well-known clinical context involves newborns, where rapid turnover of fetal hemoglobin can overwhelm the neonatal liver’s capacity to conjugate bilirubin efficiently. This can lead to elevated bilirubin levels and, in severe cases, bilirubin encephalopathy. Treatments such as phototherapy exploit the chemical properties of bilirubin, using light to isomerize and accelerate the clearance of bilirubin from the body. The science here rests on the broader heme degradation pathway, in which biliverdin sits as an upstream precursor and a component of the system that clinicians monitor during management of jaundice.

Diagnostics and biomarkers

  • Biliverdin and bilirubin levels can inform assessments of liver function and hemolysis in various clinical scenarios. While bilirubin remains the primary diagnostic readout in many cases, the relationship to biliverdin provides insight into the overall activity of heme metabolism and the capacity of glucuronidation pathways to process bilirubin for excretion.

Research and therapeutic avenues

  • Beyond conventional medicine, biliverdin’s role as a chromophore in imaging, and its potential antioxidant properties, keep it on the radar of translational research. The use of biliverdin-dependent systems in imaging and sensing reflects a broader trend toward leveraging endogenous metabolic products to advance diagnostic and therapeutic capabilities.

History and context

  • The name biliverdin derives from its origin in bile and its verdant coloration. The study of heme breakdown and the enzymes that drive the generation and transformation of biliverdin and bilirubin has a long history in biochemistry, tying together ideas about oxygen biology, detoxification, and the evolution of heme-dependent systems. The practical implications of this pathway—ranging from neonatal care to advanced imaging—show how a basic metabolic product can intersect with modern medicine and technology.

See also