Neopterin is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

belonging to the pteridine class of

heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...

s. Neopterin belongs to the chemical group known as

pteridine A pteridine is a bicyclic heterocyclic system with two nitrogen atoms at positions 1 and 4 in ring A, and two nitrogen atoms at positions 1 and 3 in ring B. Pteridines constitute a large group of heterocyclic compounds containing a wide variety o ...

s. It is synthesised by human

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s upon stimulation with the

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

interferon-gamma Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...

and is indicative of a pro-inflammatory immune status. Neopterin serves as a marker of cellular immune system activation. In humans neopterin follows a circadian (daily) and circaseptan (weekly) rhythm.

Biosynthesis

The biosynthesis of neopterin occurs in two steps from

guanosine triphosphate Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only di ...

(GTP). The first being catalyzed by GTP cyclohydrolase, which opens the ribose group. Phosphatases next catalyze the hydrolysis of the phosphate ester group.

Neopterin as disease marker

Measurement of neopterin concentrations in body fluids like

blood serum Serum () is the fluid and solvent component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum contains all proteins ex ...

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

provides information about activation of cellular immune activation in humans under the control of

T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

type 1. High neopterin production is associated with increased production of

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

, neopterin concentrations also allow to estimate the extent of

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

elicited by the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

. Increased neopterin production is found in, but not limited to, the following diseases: *

Viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, t ...

s including

human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of th ...

(HIV),

hepatitis B Hepatitis B is an infectious disease caused by the '' hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

and

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...

SARS-CoV-1 Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), previously known as severe acute respiratory syndrome coronavirus (SARS-CoV), is a strain (biology), strain of coronavirus that causes severe acute respiratory syndrome (SARS), the ...

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...

. *

Bacterial infection Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are beneficial but others can cause infectious diseases. The number of t ...

s by intracellular living

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

such as ''

Borrelia ''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted by ticks. Other species of ''Borrelia'' cause relapsing fever, and are ...

'' (

Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...

), ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'', and ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, Flagellum#bacterial, flagellated, Bacterial cellular morphologies#Helical, helical bacterium. Mutants can have a rod or curved rod shape that exhibits l ...

''. *

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The en ...

such as ''

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...

'' (

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

) *

Autoimmune diseases An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that ...

such as

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

(RA) and

systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

(SLE) *

Malignant tumor Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ...

diseases *

Allograft Allotransplant (''allo-'' meaning "other" in Ancient Greek, Greek) is the Organ transplant, transplantation of cell (biology), cells, Biological tissue, tissues, or Organ (anatomy), organs to a recipient from a genetically non-identical donor of ...

rejection episodes. *A

leukodystrophy Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word ''leukodystrophy'' comes from the Greek roots ''leuko'', "white", ''dys'', "abnormal" and ''troph'', "growth". ...

called Aicardi-Goutieres syndrome * Depression and somatization. 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 A radioimmunoassay (RIA) is an immunoassay that uses radioactive tracer, radiolabeled molecules in a stepwise formation of immune complexes. A RIA is a very sensitive in vitro assay technique used to measure concentrations of substances, usually m ...

(RIA),

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...

, or high-performance liquid chromatography (HPLC). Cavaleri et al. Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis ''Progress in Neuro-Psychopharmacology and Biological Psychiatry'' 2023. 120:110633. http://dx.doi.org/10.1016/j.pnpbp.2022.110633 It has a native

fluorescence Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colore ...

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

References

* Cavaleri et al. Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis. Progr Neuropsychopharmacol Biol Psychiatry 2023;120:110633. * Murr C, et al. Neopterin as a marker for immune system activation. Curr Drug Metabol 2002;3:175-187. * Fuchs D, et al. The role of neopterin in atherogenesis and cardiovascular risk stratification. Curr Med Chem 2009;16:4644-4653. * Sucher R, et al. Neopterin, a prognostic marker in human malignancies. Cancer Lett 2010;287:13-22. * Zeng B, et al. Serum neopterin for early assessment of severity of severe acute respiratory syndrome. Clin Immunol 2005;116(1):18-26. * Roberston J, et al. Serum neopterin levels in relation to mild and severe COVID-19. BMC Infect Dis 2020;20(1):942.

External links

NeoPterin.net

Determination of neopterin and biopterin by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in rat and human plasma, cell extracts and tissue homogenates (a protocol)
Metabolism Immunology Pteridines Triols {{biochemistry-stub