Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells

Abstract

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and find that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, and this suggests that glutamine’s ability to replenish TCA cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.

Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment

“…The complex, cyclical nature of serine and glycine metabolism can occur through cytoplasmic and mitochondrial pathways, both of which have been demonstrated to be upregulated in cancer cells (46)(47)(48)(49)(50). Additionally, serine and glycine metabolism converge on the formation of folate compounds, a target of chemotherapy for over sixty years (51)(52)(53). The significance of serine and glycine metabolism does not halt at the support of nucleotide synthesis.…”

Cancer metabolism in space and time: Beyond the Warburg effect

“…It is only re cently that an other team ad dressed this is sue in mam malian cells. In their work, Ho sios et al [16] quan ti fied the frac tion of cell mass de rived from var i ous nu tri ents. They con cluded that al though glu cose and glu t a mine had the high est and sec ond high est con sump tion rates dur ing rapid cell pro lif er a tion, re spec tively, these nu tri ents did not con tribute to the car bons used for bio mass pro duc tion.…”

“…In ter est ingly, glu t a mine de rived car bon in cor po ra tion into the bio mass was not af fected un der the same grow ing con di tions, but the in cor po ra tion of glu t a mine car bon into the non po lar ma te r ial ap prox i mately dou bled. Fi nally, the au thors stated that, if the as sump tion that cel lu lar lipids are de rived only from glu cose, glu t a mine and ex tra cel lu lar lipids is true, then up to 70% of lipid car bon came from the ex tra cel lu lar en vi ron ment, 20% to 30% came from glu cose and about 5% from glu t a mine [16]. Glycine con sump tion and ca tab o lism was re ported by oth ers to be im por tant for fast cell pro lif er a tion [54].…”

“…This leads to a sit u a tion where more ATP is used and cat a plero sis pro vides a con stant out flow of in ter me di ates [14,15]. In deed, cat a plero sis in pro lif er at ing cells is ob serv able with the syn the sis of lipids that are mainly de rived from glu cose [13,16]. A con stant sup ply of lipids is in deed nec es sary for mem brane pro duc tion [13].…”

“…Glycine con sump tion and ca tab o lism was re ported by oth ers to be im por tant for fast cell pro lif er a tion [54]. With re spect to nu cleotides, glu cose con tributed to 60%-80%, glu t a mine to 10%-20% and ser ine to ap prox i mately 15% of nu cleotide car bon con tent [16]. Of note, the con sump tion of one mol e cule of glu t a mine can fur ther pro vide 2 ni tro gen atoms that con tribute to bio mass gen er a tion [54].…”