Subcellular localization of γ-glutamyl carboxypeptidase and of folates

Shin, Y.S.; Chan, C T; Vidal, A.J.; Brody, Tom; Stokstad, E. L. R.

doi:10.1016/0304-4165(76)90326-3

Cited by 42 publications

(1 citation statement)

References 27 publications

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“…Subsequently, the discovery of these enzymes established a connection between cytoplasmic and mitochondrial one-carbon metabolism. At any given time, the mitochondria contain around 40% of total cellular folate ( Shin et al, 1976 ). The difficulty of one-carbon loaded folates to cross intracellular membranes has been recognized as a distinguishing property of one carbon metabolism.…”

Section: Introductionmentioning

confidence: 99%

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Bou Ghanem,

Hussayni,

Kadbey

et al. 2024

Front. Aging Neurosci.

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The intricate interplay of one-carbon metabolism (OCM) with various cellular processes has garnered substantial attention due to its fundamental implications in several biological processes. OCM serves as a pivotal hub for methyl group donation in vital biochemical reactions, influencing DNA methylation, protein synthesis, and redox balance. In the context of aging, OCM dysregulation can contribute to epigenetic modifications and aberrant redox states, accentuating cellular senescence and age-associated pathologies. Furthermore, OCM’s intricate involvement in cancer progression is evident through its capacity to provide essential one-carbon units crucial for nucleotide synthesis and DNA methylation, thereby fueling uncontrolled cell proliferation and tumor development. In neurodegenerative disorders like Alzheimer’s and Parkinson’s, perturbations in OCM pathways are implicated in the dysregulation of neurotransmitter synthesis and mitochondrial dysfunction, contributing to disease pathophysiology. This review underscores the profound impact of OCM in diverse disease contexts, reinforcing the need for a comprehensive understanding of its molecular complexities to pave the way for targeted therapeutic interventions across inflammation, aging and neurodegenerative disorders.

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Section: Introductionmentioning

confidence: 99%

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Bou Ghanem,

Hussayni,

Kadbey

et al. 2024

Front. Aging Neurosci.

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Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Froese

Fowler

Baumgartner

2019

J of Inher Metab Disea

307

187

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Vitamin B12 (cobalamin, Cbl) is a nutrient essential to human health. Due to its complex structure and dual cofactor forms, Cbl undergoes a complicated series of absorptive and processing steps before serving as cofactor for the enzymes methylmalonyl‐CoA mutase and methionine synthase. Methylmalonyl‐CoA mutase is required for the catabolism of certain (branched‐chain) amino acids into an anaplerotic substrate in the mitochondrion, and dysfunction of the enzyme itself or in production of its cofactor adenosyl‐Cbl result in an inability to successfully undergo protein catabolism with concomitant mitochondrial energy disruption. Methionine synthase catalyzes the methyl‐Cbl dependent (re)methylation of homocysteine to methionine within the methionine cycle; a reaction required to produce this essential amino acid and generate S‐adenosylmethionine, the most important cellular methyl‐donor. Disruption of methionine synthase has wide‐ranging implications for all methylation‐dependent reactions, including epigenetic modification, but also for the intracellular folate pathway, since methionine synthase uses 5‐methyltetrahydrofolate as a one‐carbon donor. Folate‐bound one‐carbon units are also required for deoxythymidine monophosphate and de novo purine synthesis; therefore, the flow of single carbon units to each of these pathways must be regulated based on cellular needs. This review provides an overview on Cbl metabolism with a brief description of absorption and intracellular metabolic pathways. It also provides a description of folate‐mediated one‐carbon metabolism and its intersection with Cbl at the methionine cycle. Finally, a summary of recent advances in understanding of how both pathways are regulated is presented.

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Modeling cellular compartmentation in one‐carbon metabolism

Scotti

Stella

Shearer

et al. 2013

WIREs Mechanisms of Disease

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Folate-mediated one-carbon metabolism (FOCM) is associated with risk for numerous pathological states including birth defects, cancers, and chronic diseases. Although the enzymes that constitute the biological pathways have been well described and their interdependency through the shared use of folate cofactors appreciated, the biological mechanisms underlying disease etiologies remain elusive. The FOCM network is highly sensitive to nutritional status of several B-vitamins and numerous penetrant gene variants that alter network outputs, but current computational approaches do not fully capture the dynamics and stochastic noise of the system. Combining the stochastic approach with a rule-based representation will help model the intrinsic noise displayed by FOCM, address the limited flexibility of standard simulation methods for coarse-graining the FOCM-associated biochemical processes, and manage the combinatorial complexity emerging from reactions within FOCM that would otherwise be intractable.

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Subcellular localization of γ-glutamyl carboxypeptidase and of folates

Cited by 42 publications

References 27 publications

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Modeling cellular compartmentation in one‐carbon metabolism

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Subcellular localization of γ-glutamyl carboxypeptidase and of folates

Cited by 42 publications

References 27 publications

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Vitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Modeling cellular compartmentation in one‐carbon metabolism

Contact Info

Product

Resources

About

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation