NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism

The nicotinamide adenine dinucleotide (NAD )/reduced NAD (NADH) and NADP /reduced NADP (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has b...

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Veröffentlicht in:Antioxidants & redox signaling Jg. 28; H. 3; S. 251
Hauptverfasser: Xiao, Wusheng, Wang, Rui-Sheng, Handy, Diane E, Loscalzo, Joseph
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.01.2018
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ISSN:1557-7716, 1557-7716
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Abstract The nicotinamide adenine dinucleotide (NAD )/reduced NAD (NADH) and NADP /reduced NADP (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.
AbstractList The nicotinamide adenine dinucleotide (NAD )/reduced NAD (NADH) and NADP /reduced NADP (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.
The nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) and NADP+/reduced NADP+ (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD+-consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics.SIGNIFICANCEThe nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) and NADP+/reduced NADP+ (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD+-consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics.The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism.CRITICAL ISSUESThe biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism.Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD+ precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.FUTURE DIRECTIONSAdditional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD+ precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.
Author Xiao, Wusheng
Handy, Diane E
Wang, Rui-Sheng
Loscalzo, Joseph
Author_xml – sequence: 1
  givenname: Wusheng
  surname: Xiao
  fullname: Xiao, Wusheng
  organization: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
– sequence: 2
  givenname: Rui-Sheng
  surname: Wang
  fullname: Wang, Rui-Sheng
  organization: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
– sequence: 3
  givenname: Diane E
  surname: Handy
  fullname: Handy, Diane E
  organization: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
– sequence: 4
  givenname: Joseph
  surname: Loscalzo
  fullname: Loscalzo, Joseph
  organization: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28648096$$D View this record in MEDLINE/PubMed
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Keywords redox state
NAD(H)
reductive stress
NADP(H)
oxidative stress
cellular metabolism
Language English
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PublicationTitle Antioxidants & redox signaling
PublicationTitleAlternate Antioxid Redox Signal
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Snippet The nicotinamide adenine dinucleotide (NAD )/reduced NAD (NADH) and NADP /reduced NADP (NADPH) redox couples are essential for maintaining cellular redox...
The nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) and NADP+/reduced NADP+ (NADPH) redox couples are essential for maintaining cellular redox...
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SubjectTerms Animals
Energy Metabolism
Extracellular Space
Gene Expression Regulation, Enzymologic
Homeostasis
Humans
Intracellular Space
Metabolic Networks and Pathways
NAD - metabolism
NADP - metabolism
Oxidation-Reduction
Oxidative Stress
Signal Transduction
Title NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism
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