Neopterin
Encyclopedia
Neopterin is a catabolic product of guanosine triphosphate
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 (GTP), a purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

.

Neopterin belongs to the chemical group known as pteridine
Pteridine
Pteridine is a chemical compound composed of fused pyrimidine and pyrazine rings. A pteridine is also a group of heterocyclic compounds containing a wide variety of substitutions on this structure. Pterins and flavins are classes of substituted pteridines that have important biological...

s. It is synthesised by macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s upon stimulation with the cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 interferon-gamma
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...

 and is indicative of a pro-inflammatory immune status. Neopterin serves as a marker of cellular immune system
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...

 activation.

Neopterin as disease marker

Measurement of neopterin concentrations in body fluids like blood serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

, cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 or urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 provides information about activation of cellular immune activation in humans under the control of T helper cells type 1. High neopterin production is associated with increased production of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

, neopterin concentrations also allow to estimate the extent of oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

 elicited by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

.

Increased neopterin production is found in, but not limited to, the following diseases:
  • viral infections including human immunodeficiency virus (HIV), hepatitis B and hepatitis C
    Hepatitis C
    Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...


  • bacterial infections by intracellular living bacteria
    Bacteria
    Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

     such as Borrelia
    Borrelia
    Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

     (Lyme Disease
    Lyme disease
    Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

    ) and Mycobacterium tuberculosis
    Mycobacterium tuberculosis
    Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...


  • parasites
    Parasitism
    Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...

     such as Plasmodium
    Plasmodium
    Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...

     (malaria
    Malaria
    Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

    )

  • autoimmune diseases such as rheumatoid arthritis
    Rheumatoid arthritis
    Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

     (RA) and systemic lupus erythematosus
    Systemic lupus erythematosus
    Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

     (SLE)

  • malignant tumor diseases

  • allograft rejection episodes.

  • A leukodystrophy
    Leukodystrophy
    Leukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...

     called Aicardi-Goutieres syndrome
    Aicardi-Goutieres syndrome
    Aicardi–Goutières syndrome is a rare genetic disorder. It is also known as Cree encephalitis and pseudo-TORCH syndrome, both of which were once considered separate disorders. It is a type of leukodystrophy and is usually fatal within the first few years...



Neopterin concentrations usually correlate with the extent and activity of the disease, and are also useful to monitor during therapy in these patients. Elevated neopterin concentrations are among the best predictors of adverse outcome in patients with HIV infection, in cardiovascular disease and in various types of cancer.

In the laboratory it is measured by radioimmunoassay
Radioimmunoassay
Radioimmunoassay is a very sensitive in vitro assay technique used to measure concentrations of antigens by use of antibodies...

 (RIA), ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

, or high-performance liquid chromatography (HPLC). It has a native fluorescence
Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...

of wavelength excitation at 353 nm and emission at 438 nm, rendering it readily detected.

External links

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