Cycloleucine Explained

Cycloleucine is a non-proteinogenic amino acid. It could be classified as a cyclopentane derivative of norleucine, having two hydrogen atoms less. The α-carbon atom is not a stereocenter. Cycloleucine is a non-metabolisable amino acid that specifically and reversibly inhibits nucleic acid methylation. It is widely used in biochemical experiments.[1]

In 2007, a research study had shown that cycloleucine can lower S-adenosyl methionine (SAM) levels in primary rat 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) and lower SAM levels in pyrazole hepatocytes had shown an increased amount of cell apoptosis when compared to control hepatocytes.[2]

In a 2015 study on the role of N6-methyladenosine (m6A) demethylation on adipogenesis, researchers treated porcine adipocytes with increasing concentrations of cycloleucine. The researchers measured mRNA concentration of m6A using the dot blot method, and the results showed that cycloleucine increased adipocyte growth by blocking methylation by inhibiting m6A levels relative to the control adipocytes.[3]

A 2022 study showed that cycloleucine inhibits porcine oocyte and embryo development. Researchers cultured porcine oocytes and isolated cumulus cells from their cumulus cell complexes, after which the cells were cultured in vitro with cycloleucine in increasing concentrations. The samples were monitored under fluorescence microscopy, with the results showing positive relationship between cycloleucine concentration and decreased viability and survival rate for oocytes.[4]

Notes and References

  1. Caboche M, Bachellerie JP . RNA methylation and control of eukaryotic RNA biosynthesis. Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation . European Journal of Biochemistry . 74 . 1 . 19–29 . March 1977 . 856572 . 10.1111/j.1432-1033.1977.tb11362.x . free .
  2. Zhuge J, Cederbaum AI . Depletion of S-adenosyl-l-methionine with cycloleucine potentiates cytochrome P450 2E1 toxicity in primary rat hepatocytes . Archives of Biochemistry and Biophysics . 466 . 2 . 177–85 . October 2007 . 17640612 . 2040067 . 10.1016/j.abb.2007.06.007 .
  3. Wang . Xinxia . Zhu . Linna . Chen . Jingqing . Wang . Yizhen . 2015-04-03 . mRNA m6A Methylation Downregulates Adipogenesis In Porcine Adipocytes . Biochemical and Biophysical Research Communications . en . 459 . 2 . 201–207 . 10.1016/j.bbrc.2015.02.048 . 25725156 . 0006-291X.
  4. Zhang . Meng . Zhang . Sheng . Zhai . Yanhui . Han . Yu . Huang . Rong . An . Xinglan . Dai . Xiangpeng . Li . Ziyi . 2022-02-01 . Cycloleucine Negatively Regulates Porcine Oocyte Maturation And Embryo Development By Modulating N6-Methyladenosine And Histone Modifications . Theriogenology . en . 179 . 128–140 . 10.1016/j.theriogenology.2021.11.024 . 34864563 . 244746381 . 0093-691X.