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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

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Frontiers of Medicine  2021, Vol. 15 Issue (5): 679-692   https://doi.org/10.1007/s11684-021-0866-1
  本期目录
Potential of electron transfer and its application in dictating routes of biochemical processes associated with metabolic reprogramming
Ronghui Yang1,3, Guoguang Ying4,5,6(), Binghui Li1,2,3()
1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
2. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
3. Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University, Beijing 100069, China
4. Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
5. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China
6. National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
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Abstract：

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
Key words： metabolic reprogramming    potential of electron transfer    cell proliferation    aerobic glycolysis    cancer metabolism
收稿日期: 2020-12-01      出版日期: 2021-11-01
Corresponding Author(s): Guoguang Ying,Binghui Li   
 引用本文:   
. [J]. Frontiers of Medicine, 2021, 15(5): 679-692.
Ronghui Yang, Guoguang Ying, Binghui Li. Potential of electron transfer and its application in dictating routes of biochemical processes associated with metabolic reprogramming. Front. Med., 2021, 15(5): 679-692.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-021-0866-1
https://academic.hep.com.cn/fmd/CN/Y2021/V15/I5/679
Fig.1  
Metabolites Formula Y Y¯
Carbohydrate Glucose C6H12O6 24 4.00
Ribose C5H10O5 20 4.00
Fructose C6H12O6 24 4.00
Glyceraldehyde C3H6O3 12 4.00
Glyceric acid C3H6O4 10 3.33
Pyruvate C3H4O3 10 3.33
Lactate C3H6O3 12 4.00
Oxaloacetate C4H4O5 10 2.50
Malate C4H6O5 12 3.00
Fumarate C4H4O4 12 3.00
Succinate C4H6O4 14 3.50
α-Ketoglutarate C5H6O5 16 3.20
Citrate C6H8O7 18 3.00
Nucleobase Adenine C5H5N5 10 2.00
Guanine C5H5N5O 8 1.60
Cytosine C4H5N3O 10 2.50
Thymine C5H6N2O2 16 3.20
Uracil C4H4N2O2 10 2.50
Ribonucleoside Adenosine C10H13N5O4 30 3.00
Guanosine C10H13N5O5 28 2.80
Cytidine C9H13N3O5 30 3.33
Uridine C9H12N2O6 30 3.33
Deoxy-ribonucleoside Deoxyadenosine C10H13N5O3 32 3.20
Deoxyguanosine C10H13N5O4 30 3.00
Deoxycytidine C9H13N3O4 32 3.56
Deoxythymidine C10H14N2O5 38 3.80
Non-essential amino acids Glycine C2H5NO2 6 3.00
Serine C3H7NO3 10 3.33
Aspartate C4H7NO4 12 3.00
Asparagine C4H8N2O3 12 3.00
Glutamine C5H10N2O3 18 3.60
Glutamate C5H9NO4 18 3.60
Alanine C3H7NO2 12 4.00
Proline C5H9NO2 22 4.40
Semi-essential amino acids Histidine C6H9N3O2 20 3.33
Arginine C6H14N4O2 22 3.67
Essential amino acids Threonine C4H9NO3 16 4.00
Cysteinea C3H7NO2S 16 5.33
Methioninea C5H11NO2S 28 5.60
Lysine C6H14N2O2 28 4.66
Valine C5H11NO2 24 4.8
Leucine C6H13NO2 30 5.00
Isoleucine C6H13NO2 30 5.00
Tryptophan C11H12N2O2 46 4.18
Phenylalanine C9H11NO2 40 4.44
Tyrosine C9H11NO3 38 4.22
Acetyl-CoA Acetate C2H4O2 8 4.00
Lipid components Glycerol C3H8O3 14 4.67
Palmitate C16H32O2 92 5.75
Farnesolb C15H26O 84 5.60
End metabolites Carbon dioxide CO2 0
Water H2O 0
Urea/ammonia CH4N2O/NH3 0
Electron acceptor Oxygen O2 –4
Tab.1  
Pathways Initial substrates Final products ΔY
ATP generation Electrons+ 4H+ + O2 H2O ΔYETC<0
Glucose Pyruvate ΔYPyr-4,Glc = –4
Pyruvate CO2 ΔYCO2-20,Pyr = –20
Pyruvate Lactate ΔYLac+4,Pyr = +4
Citric acid cycle intermediates CO2 ΔYCAC-<0
Nucleotide biosynthesis Glucose Ribose+ CO2 ΔYoPPP Ribose-4, Glc= –4
Glucose Ribose ΔYnPPP Ribose_0, Glc= 0
Ribose+ amino acids Nucleotides ΔYNuc-<0
Sugar biosynthesis Glutamine Sugar ΔYSug-6,Gln = –6
Glucose Sugar ΔYSug 0,Glc = 0
Amino acid biosynthesis Glutamine Serine ΔYSer-8,Gln = –8
Glucose Serine ΔYSer-2,Glc = –2
Glutamine Alanine ΔYAla-6,Gln = –6
Glucose Alanine ΔYAla 0,Glc = 0
Glutamine Aspartate ΔYAsp-6,Gln = –6
Glucose Aspartate ΔYAsp 0,Glc = 0
Glutamine Proline ΔYPro+4,Gln = +4
Glucose Proline ΔYPro-2,Glc = –2
Lipid biosynthesis Glutamine Glycerol-3P ΔYGlo-4,Gln = –4
Glucose Glycerol-3P ΔYGlo+2,Glc = +2
Glutamine Palmitate+ Aspartate ΔY(Palm,Asp)+5.5,Gln = +5.5
Glutamine Palmitate+ Lactate ΔY(Palm,Lac)+5.5,Gln = +5.5
Glutamine Palmitate+ CO2 ΔY(Palm,CO2)-6.5,Gln = –6.5
Glucose Palmitate+ Aspartate ΔY(Palm,Asp)-0.5,Glc = –0.5
Glucose Palmitate+ Lactate ΔY(Palm,Lac)-0.5,Glc = –0.5
Glucose Palmitate+ CO2 ΔY(Palm,CO2)-12.5,Glc = –12.5
Tab.2  
Fig.2  
Nutrients Products ΔY ΔYAc,Nutr ΔYGMR
Acetate Ac-CoA 0 0 +7.5
Leucine 3Ac-CoA –6 –2 +5.5
Glucose 2Ac-CoA –8 –4 +3.5
Lactate Ac-CoA –4 –4 +3.5
Alanine Ac-CoA –4 –4 +3.5
Aspartate Ac-CoA –4 –4 +3.5
Tyrosine 3Ac-CoA –14 –4.67 +2.83
Phenylalanine 3Ac-CoA –16 –5.33 +2.17
Tryptophan 3Ac-CoA+Formyl-THF –18 –6 +1.5
Lysine 2Ac-CoA –12 –6 +1.5
Isoleucine 2Ac-CoA –14 –7 +0.5
Tab.3  
Fig.3  
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