PMID- 37295387
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20231121
IS  - 1879-0534 (Electronic)
IS  - 0010-4825 (Linking)
VI  - 162
DP  - 2023 Aug
TI  - Modeling of glycosaminoglycan biosynthesis in intervertebral disc cells.
PG  - 107039
LID - S0010-4825(23)00504-8 [pii]
LID - 10.1016/j.compbiomed.2023.107039 [doi]
AB  - Loss of proteoglycan (PG) is a potential factor responsible for degeneration of 
      the intervertebral disc (IVD). PG consists of a core protein with covalently 
      attached glycosaminoglycan (GAG) chains. The objective of this study was to 
      develop a mathematical model of GAG biosynthesis to investigate the effects of 
      glycolytic enzymes on GAG biosynthesis of IVD cells. A new mathematical model of 
      GAG biosynthesis was developed for IVD cells by incorporating biosynthesis of 
      uridine diphosphate-sugars into the glycolytic pathway. This new model showed 
      good agreement between the model predictions of intracellular ATP content and GAG 
      biosynthesis and experimental data measured at different external glucose levels. 
      The quantitative analyses demonstrated that GAG biosynthesis may be sensitive to 
      the activities of hexokinase (HK) and phosphofructokinase (PFK), especially at 
      low glucose supply, with GAG biosynthesis being significantly enhanced by a 
      slight increase in activities of HK and PFK. This suggests that metabolic 
      reprogramming could be a potential strategy for promoting PG biosynthesis in IVD 
      cells. Furthermore, it was shown that GAG biosynthesis may be promoted by 
      increasing intracellular glutamine concentration or activity of 
      glutamine:fructose-6-phosphate amidotransferase in the hexamine pathway. This 
      study provides a better understanding of the relationship between glycolysis and 
      PG biosynthesis in IVD cells. The theoretical framework developed in this study 
      is useful for studying the role of glycolysis in disc degeneration and developing 
      new preventive and treatment strategies for degeneration of the IVD.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Huang, Chun-Yuh
AU  - Huang CY
AD  - Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA. 
      Electronic address: c.huang1@miami.edu.
FAU - Loo, Daniela M
AU  - Loo DM
AD  - Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA.
FAU - Gu, Weiyong
AU  - Gu W
AD  - Department of Mechanical and Aerospace Engineering, University of Miami, Coral 
      Gables, FL, USA.
LA  - eng
PT  - Journal Article
DEP - 20230524
PL  - United States
TA  - Comput Biol Med
JT  - Computers in biology and medicine
JID - 1250250
RN  - 0RH81L854J (Glutamine)
RN  - 0 (Glycosaminoglycans)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - Glutamine/metabolism
MH  - *Intervertebral Disc
MH  - *Intervertebral Disc Degeneration
MH  - Glycosaminoglycans/metabolism
MH  - Glucose/metabolism
OTO - NOTNLM
OT  - Glycolysis
OT  - Glycosaminoglycan
OT  - Intervertebral disc
OT  - Proteoglycan
COIS- Declaration of competing interest All authors have declared that no conflict of 
      interest exist.
EDAT- 2023/06/10 15:14
MHDA- 2023/06/19 13:08
CRDT- 2023/06/09 18:12
PHST- 2022/10/05 00:00 [received]
PHST- 2023/05/05 00:00 [revised]
PHST- 2023/05/12 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/06/10 15:14 [pubmed]
PHST- 2023/06/09 18:12 [entrez]
AID - S0010-4825(23)00504-8 [pii]
AID - 10.1016/j.compbiomed.2023.107039 [doi]
PST - ppublish
SO  - Comput Biol Med. 2023 Aug;162:107039. doi: 10.1016/j.compbiomed.2023.107039. Epub 
      2023 May 24.