Mitochondrial malic enzyme activity is much higher in mitochondria from cortical synaptic terminals compared with mitochondria from primary cultures of cortical neurons or cerebellar granule cells

McKenna, Mary C.; Stevenson, Joseph; Huang, Xueli; Tildón, J. Tyson; Zielke, Carol L.; Hopkins, Irene B.

doi:10.1016/s0197-0186(99)00148-5

Cited by 74 publications

(49 citation statements)

References 57 publications

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“…Like IDPc, cytosolic ME is also not up-regulated in mouse cells deleted for G6PD [67]. The mitochondrial isoform plays an important role in the pyruvaterecycling pathway and in maintaining the intramitochondrial GSH in the brain [90]. In pancreatic islets, the mitochondrial pyruvatemalate shuttle could contribute far more to NADPH generation than the cytosolic pentose phosphate pathway [91].…”

Section: Two Nadpmentioning

confidence: 99%

The power to reduce: pyridine nucleotides – small molecules with a multitude of functions

Pollak

Dölle

Ziegler

2007

Biochemical Journal

617

550

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The pyridine nucleotides NAD and NADP play vital roles in metabolic conversions as signal transducers and in cellular defence systems. Both coenzymes participate as electron carriers in energy transduction and biosynthetic processes. Their oxidized forms, NAD + and NADP + , have been identified as important elements of regulatory pathways. In particular, NAD + serves as a substrate for ADP-ribosylation reactions and for the Sir2 family of NAD + -dependent protein deacetylases as well as a precursor of the calcium mobilizing molecule cADPr (cyclic ADP-ribose). The conversions of NADP + into the 2 -phosphorylated form of cADPr or to its nicotinic acid derivative, NAADP, also result in the formation of potent intracellular calcium-signalling agents. Perhaps, the most critical function of NADP is in the maintenance of a pool of reducing equivalents which is essential to counteract oxidative damage and for other detoxifying reactions. It is well known that the NADPH/NADP + ratio is usually kept high, in favour of the reduced form. Research within the past few years has revealed important insights into how the NADPH pool is generated and maintained in different subcellular compartments. Moreover, tremendous progress in the molecular characterization of NAD kinases has established these enzymes as vital factors for cell survival. In the present review, we summarize recent advances in the understanding of the biosynthesis and signalling functions of NAD(P) and highlight the new insights into the molecular mechanisms of NADPH generation and their roles in cell physiology.

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Section: Two Nadpmentioning

confidence: 99%

The power to reduce: pyridine nucleotides – small molecules with a multitude of functions

Pollak

Dölle

Ziegler

2007

Biochemical Journal

617

550

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“…In the present study, we identified (with at least 3 peptides) 23 proteins with significantly increased (Table 1) and 23 proteins with decreased ( Table 2) (1) - (Chihara et al, 2007), (2) - (Folci et al, 2014), (3) - (Chen et al, 2002), (4) - (Tanaka et al, 2000), (5) - (Ding and Shen, 2008), (6) - (Na et al, 2012), (7) - (Lyon et al, 2007), (8) - (Sweatt et al, 2004), (9) - (Bahn et al, 2002), (10) - (Manya et al, 1998), (11) - (Kamada et al, 2003), (12) - (McKenna et al, 2000), (13) - (Christel et al, 2012), (GO) -According to Gene Ontology database. …”

Section: Functional Clusters Of Altered Proteinsmentioning

confidence: 99%

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

et al. 2017

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Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH 2 induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established.In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with Magnetic Resonance Angiography 5 weeks after the surgery.Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analysed with label free nanoUHPLC-MS/MS.

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“…In the last few years, however, several groups have found malic enzyme in synaptosomes (Cruz et al, 1998;McKenna et al, 2000) and in cultured neurons (Vogel et al, 1998;McKenna et al, 2000;Hassel and Bråthe, 2000b). Malic enzyme, which reversibly catalyzes carboxylation of pyruvate to malate, could therefore explain the pyruvatecarboxylating activity of neurons, although most researchers have considered the enzyme to operate in the decarboxylating direction in the brain (Vogel et al, 1998;Hertz et al, 1999;McKenna et al, 2000).…”

Section: A Neuronal Enzyme That May Carboxylate Pyruvate: Malic Enzymementioning

confidence: 99%

Pyruvate carboxylation in neurons

Hassel

2001

J of Neuroscience Research

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Carboxylation of pyruvate in the brain was for many years thought to occur only in glia, an assumption that formed much of the basis for the concept of the glutamine cycle. It was shown recently, however, that carboxylation of pyruvate to malate occurs in neurons and that it supports formation of transmitter glutamate. The role of pyruvate carboxylation in neurons is to ensure tricarboxylic acid cycle activity by compensating for losses of alpha-ketoglutarate that occur through release of transmitter glutamate and GABA; these amino acids are alpha-ketoglutarate derivatives. Available data suggest that neuronal pyruvate carboxylation is quantitatively important. But because there is no net CO(2) fixation in the brain, pyruvate carboxylation must be balanced by decarboxylation of malate or oxaloacetate. Such decarboxylation occurs in both neurons and astrocytes. Several in vitro studies have shown a neuroprotective effect of pyruvate supplementation. Pyruvate carboxylation may be one mechanism through which such treatment is effective, because pyruvate carboxylation through malic enzyme is active during energy deficiency and leads to an increase in the level of dicarboxylates that can be metabolized through the tricarboxylic acid cycle for ATP production.

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Mitochondrial malic enzyme activity is much higher in mitochondria from cortical synaptic terminals compared with mitochondria from primary cultures of cortical neurons or cerebellar granule cells

Cited by 74 publications

References 57 publications

The power to reduce: pyridine nucleotides – small molecules with a multitude of functions

The power to reduce: pyridine nucleotides – small molecules with a multitude of functions

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Pyruvate carboxylation in neurons

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