Nature: Amino acid metabolism changes the regulatory mechanism of tumor suppression.

Serine, Glycine, and other non-essential amino acids are closely associated with tumor development, so inhibiting the activity and utilization of these non-essential amino acids can be used as a potential tool for cancer treatment.
, however, the molecular biological mechanisms and possible effects on lipid metabolism are not yet known.
recently, Professor Christian M. Metallo of the University of California, San Diego, published a research paper entitled Serine restriction alters sphingolipid diversity to constrain tumour growth in Nature.
The in vitro study of the metabolic process of amino acids and biosynthetics of esters in non-walled tumor cells, as well as dietary amino acid interventions in HCT116 heterogenous transplant mice, revealed that the lack of serine inhibition of tumors was caused by the mixing of serine palmyl metastase (SPT) and abnormal deoxysphingolipids.
non-walled cell growth is a typical feature of invasive tumors that can help them influence the growth and survival of tumor cells by recalcuiting metabolic processes.
inhibition of mitochondrial acetone acid carrier (MPC) by USUK5099 as an inhibitor can significantly reduce the amount of alanine in non-walled cells.
Their metabolic tracer study using glucose (U-13C6) found that treating the sphere of HCT116 cells (colon cancer cell line) with UK5099 increased the synthesis of serine and inhibited the glucose oxidation process, significantly increasing the proportion of serine/alanine in cells.
, they hypothesized that inhibiting MPC promoted the oxidation and quantification of citric acid in HCT116 cells, and observed a significant increase in the amount of propulsion of alanine to terabytes (TCA) after UK5099 treatment.
tumor cells effectively bypass the MPC by synthesized, transporting and decomposing alanine through mitochondrials, thus avoiding the abundance of alanine and enhancing its growth in non-walled environments (Figure 1).
they determined that the decrease in alanine levels was a potential mechanism to inhibit MPC's ability to enhance non-walled growth of tumor cells.
Because of the high exchangeability of non-essential amino acids such as alanine, serine, and glycine in cytoplasms and mitochondrials, the researchers compared alanine with other non-essential amino acids by artificially controlling the utilization of serine and glycine in spherical cultures and quantitatively analyzing biomass.
It is worth noting that the removal of serine, similar to or more than the level of alanine supplementation, slows the growth of tumor spheres to some extent, and in the absence of serine or formate, glycine levels are inhibited.
, after measuring the Km values of several enzymes by changing the concentration of serine, it was found that the affinity of serine palmyl transferase SPT on serine was significantly affected by the serine content.
SPT has enzyme hybridity, can not act on serine, but the use of alanine for the substrate to produce toxic deoxygenated glycolipid, and inhibit the growth of HCT116 sphere (non-walled state).
by removing serine and glycine, the level of toxic deoxygenated lipids can be reduced by supplementing alanine.
In this we see that the lack of serine and glycine, or the supplementation of large amounts of alanine, can lead to abnormal deoxygenation lipids, thereby inhibiting the non-walled growth of HCT116 cells.
Then, in order to explore whether the synthesis of deoxygenates in the amino acid metabolism process led to changes in the growth status of non-walled cells, the team directly targeted SPT with myoglobulin and quantified the effect of this on HCT116 cell growth.
Tests in colon cancer cells have found that when alanine is present, the inhibition of SPT can help cells restore non-walled growth, further linking the regulation of alanine metabolic levels to potential deoxysphinganine.
deoxycycline alcohol is cytotoxic when N-adylification and the formation of deoxygenation DHCER, the use of fumonisin B1 to inhibit the synthesis of ceramide can have a similar effect to the use of myoprotein to help non-wall cells grow (Figure 2).
, they provided normal control group feed or isotrophic feed (-SC group) to mice with colon cancer HCT116 heterogenous transplant tumors, respectively.
-SC group fed mice with smaller tumors and changes in the levels of serine, glycine and alanine in the body (lower levels of serine and glycine and higher levels of alanine).
, the difference in deoxygenation levels was most pronounced when comparing lipids in tumors isolated in the control group and mice fed with -SC.
tumors in mice fed in the A-SC group, the levels of deoxygenated pyrethrol, deoxygenated DHCER and deoxycycline increased 5-8 times compared to the control group.
, the lack of serine and glycine can cause toxic deoxygenation esters to accumulate in tumors, thereby inhibiting the growth of tumor cells.
the role of serine palmyl transferase SPT in amino acid metabolism, the study revealed the effects of enzyme mixing on the function of biological systems.
deoxygenate may act as a stress signal, affecting the composition of the cell membrane and cell growth.
although further research is needed to explain why these molecules are toxic to cancer cells, SPT, as a lipid metabolic response switch, may be a potential new anti-cancer tool.
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