Cycloleucine is a non-proteinogenic

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

. It could be classified as a cyclic derivate of

norleucine Norleucine (abbreviated as Nle) is an amino acid with the formula CH3(CH2)3CH(NH2)CO2H. A systematic name for this compound is 2-aminohexanoic acid. The compound is an isomer of the more common amino acid leucine. Like most other α-amino acids, ...

, having two hydrogen atoms less. Leading structure is a

cyclopentane Cyclopentane (also called C pentane) is a highly flammable alicyclic hydrocarbon with chemical formula C5H10 and CAS number 287-92-3, consisting of a ring of five carbon atoms each bonded with two hydrogen atoms above and below the plane. It occur ...

-ring. The α-carbon atom is not a stereocenter. Cycloleucine is a non-metabolisable amino acid and is a specific and reversible

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main cl ...

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

, and as such is widely used in

biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology an ...

experiments. In 2007, a research study performed on primary rat hepatocytes had shown that cycloleucine can lower

S-Adenosyl_methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...

(SAM) levels in control hepatocytes by inhibiting the conversion of 5'-methylthioadenosine to SAM through the methionine salvage pathway. Cycloleucine treatment in conjunction with higher levels of cytochrome P450 2E1 (

CYP2E1 Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, includ ...

) and lower SAM levels in pyrazole hepatocytes had shown an increased amount of cell

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

when compared to control hepatocytes. In a 2015 study on the role of N6-methyladenosine ( m6A) demethylation on

adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocy ...

, researchers treated porcine adipocytes with increasing concentrations of cycloleucine. The researchers measured mRNA concentration of m6A using the

Dot Blot A dot blot (or slot blot) is a technique in molecular biology used to detect proteins. It represents a simplification of the western blot method, with the exception that the proteins to be detected are not first separated by electrophoresis. Inste ...

method, and the results showed that cycloleucine increased adipocyte growth by blocking methylation by inhibiting m6A levels relative to the control adipocytes. Building on the findings on cycloleucine’s role in the inhibition of N6-methyladenosine activity a 2022 study showed that cycloleucine inhibits porcine oocyte and embryo development. Researchers cultured porcine oocytes and isolated cumulus cells from their

cumulus cell The cumulus oophorus, (discus proligerus), is a cluster of cells that surround the oocyte both in the ovarian follicle and after ovulation. In the antral follicle, it may be regarded as an extension of the membrana granulosa. The innermost layer o ...

complexes, after which the cells were cultured in vitro with cycloleucine in increasing concentrations.The samples were monitored under

fluorescence microscopy A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microsc ...

, with the results showing positive relationship between cycloleucine concentration and decreased viability and survival rate for oocytes.

References

{{reflist Cyclic amino acids Cyclopentanes