ATP‐Citrate Lyase and Other Enzymes of Acetyl‐CoA Metabolism in Fractions of Small and Large Synaptosomes from Rat Brain Hippocampus and Cerebellum

Szutowicz, Andrzej; Harris, Norman F.; Srere, Paul A.; Crawford, Isaac L.

doi:10.1111/j.1471-4159.1983.tb00854.x

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…Otherwise, lower activities of glutamate enzymes and higher AChE were detected in ''small'' synaptosomes respect to ''large'' ones, confirming the cholinergic nature of SS [62]. This observation is also clearly shown by Szutowicz et al [12], that detected high level of choline acetyltransferase (ChAT) activity in hippocampal SS, being both AChE and ChAT marker enzymes of septo-hippocampal nerve terminals [63].…”

Section: Synaptosomal Metabolism At 2 Months Of Agesupporting

confidence: 71%

“…The so-called ''large'' and ''small'' synaptosomal fractions were isolated from the cerebellum of a single animal, according to the procedure of Israël and Whittaker [10] for guinea pig cerebellum as modified by Szutowicz et al [12] for pooled hippocampi of rat and by an analytical technique adapted to single animal, as described in details by Gorini et al [13] and Villa et al [14].…”

Section: Preparation Of the ''Crude'' Synaptosomal Fraction And ''Crumentioning

confidence: 99%

“…This ''analytical'' sub-fractionation technique was successfully previously utilized by us to isolate the two synaptosomal populations from the cerebellum of Macaca fascicularis (Cynomolgus monkey) [11] and, with appropriate modifications, to isolate the analogous preparations from the rat hippocampus [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

2014

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Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

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Section: Synaptosomal Metabolism At 2 Months Of Agesupporting

confidence: 71%

Section: Preparation Of the ''Crude'' Synaptosomal Fraction And ''Crumentioning

confidence: 99%

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Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

2014

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“…The activities of ACL and ChAT were also significantly correlated in fractions of large and small synaptosomes isolated from rat hippocampus and cerebellum [70]. No such interdependence was demonstrated for PDHC.…”

Section: Intercellular Compartmentalization Of Brain Acetyl-coa Metabmentioning

confidence: 99%

Early and Late Pathomechanisms in Alzheimer’s Disease: From Zinc to Amyloid-β Neurotoxicity

et al. 2016

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There are several systemic and intracerebral pathologic conditions, which limit provision and utilization of energy precursor metabolites in neuronal cells. Energy deficits cause excessive depolarization of neuronal cells triggering glutamate-zinc evoked excitotoxic cascade. The intracellular zinc excess hits several intraneuronal targets yielding collapse of energy balance and impairment functional and structural impairments cholinergic neurons. Disturbances in metabolism of acetyl-CoA, which is a direct precursor for energy, acetylcholine, N-acetyl-l-aspartate and acetylated proteins synthesis, play an important role in these pathomechanisms. Disruption of brain homeostasis activates slow accumulation of amyloid-β1−42, which extra and intracellular oligomeric deposits disrupt diverse transporting and signaling processes in all membrane structures of the cell. Both neurotoxic signals may combine aggravating detrimental effects on neuronal cell. Different neuroglial and neuronal cell types may display differential susceptibility to similar pathogenic insults depending on specific features of their energy and functional parameters. This review, basing on findings gained from cellular and animal models of Alzheimer’s disease, discusses putative energy/acetyl-CoA dependent mechanism in early and late stages of neurodegeneration.

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“…The newly synthesized ACh is loaded into synaptic vesicles by vesicular ACh transporter (VAChT). ACL and ChAT are present in cholinergic neurons of rat brain, and their activities are mostly found in synaptosomes (Szutowicz et al, 1983). However, how the cholinergic machinery is spatially regulated for morphogenesis and neurotransmission remains unknown.…”

Section: Introductionmentioning

confidence: 99%

BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis

et al. 2015

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Synthesis and release of neurotransmitters such as acetylcholine (ACh) are key to synaptic function. However, little is known about the spatial regulation of their synthesizing machinery. Here, we demonstrate that ataxia-related protein BNIP-H/Caytaxin links kinesin-1 (KLC1) to ATP citrate lyase (ACL), a key enzyme for ACh synthesis, and transports it toward neurite terminals. There, BNIP-H/ACL complex synergistically recruits another enzyme choline acetyltransferase (ChAT), leading to enhanced secretion of ACh. ACh then activates MAPK/ERK via muscarinic receptors to promote neurite outgrowth. In mice deficient in BNIP-H, ACL fails to interact with KLC1, and formation of the ACL/ChAT complex is prevented, whereas the disease-associated BNIP-H mutation fails to target ACL for neurite outgrowth. Significantly, Bnip-h knockdown in zebrafish causes developmental defect in motor neurons through impaired cholinergic pathway, leading to motor disorder. Therefore, precise targeting of the cholinergic machinery through BNIP-H is essential for the local production of ACh for morphogenesis and neurotransmission.

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ATP‐Citrate Lyase and Other Enzymes of Acetyl‐CoA Metabolism in Fractions of Small and Large Synaptosomes from Rat Brain Hippocampus and Cerebellum

Cited by 14 publications

References 25 publications

Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

Energy Metabolism of Synaptosomes from Different Neuronal Systems of Rat Cerebellum During Aging: A Functional Proteomic Characterization

Early and Late Pathomechanisms in Alzheimer’s Disease: From Zinc to Amyloid-β Neurotoxicity

BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis

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