31P Nuclear Magnetic Resonance Studies of Phosphoglyceride Metabolism in Developing and Degenerating Brain

Pettegrew, Jay W.; Kopp, Stephen J.; Minshew, Nancy J.; Glonek, Thomas; Feliksik, Janice M.; Tow, June P.; Cohen, M.

doi:10.1097/00005072-198707000-00002

Cited by 154 publications

(71 citation statements)

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“…In vitro and in vivo assays have determined that the most abundant components of the PME signal are the membrane precursors phosphoethanolamine (PE) and PC, but the signal also includes various sugar and inositol phosphates ( Figure 3). 105,106 Because of the multiple membrane metabolites represented in this signal, alterations in PME levels are thought to reflect concurrent alterations in phospholipid membrane metabolism. Specifically, an increase of the PME peak has been suggested to indicate an increased rate of membrane phospholipid turnover.…”

Section: Impaired Phospholipid Metabolism In Bipolar Disordermentioning

confidence: 99%

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

2005

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Magnetic resonance spectroscopy (MRS) affords a noninvasive window on in vivo brain chemistry and, as such, provides a unique opportunity to gain insight into the biochemical pathology of bipolar disorder. Studies utilizing proton ( 1 H) MRS have identified changes in cerebral concentrations of N-acetyl aspartate, glutamate/glutamine, choline-containing compounds, myo-inositol, and lactate in bipolar subjects compared to normal controls, while studies using phosphorus ( 31 P) MRS have examined additional alterations in levels of phosphocreatine, phosphomonoesters, and intracellular pH. We hypothesize that the majority of MRS findings in bipolar subjects can be fit into a more cohesive bioenergetic and neurochemical model of bipolar illness that is both novel and yet in concordance with findings from complementary methodological approaches. In this review, we propose a hypothesis of mitochondrial dysfunction in bipolar disorder that involves impaired oxidative phosphorylation, a resultant shift toward glycolytic energy production, a decrease in total energy production and/or substrate availability, and altered phospholipid metabolism. Molecular Psychiatry (2005) 10, 900-919.

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Section: Impaired Phospholipid Metabolism In Bipolar Disordermentioning

confidence: 99%

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

2005

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“…There also is solid evidence for a fundamental alteration in membrane phospholipid composition and metabolism in AD. [111][112][113][114][115][116][117][118][119] Of considerable importance is the observation that the membrane molecular changes actually precede cognitive decline. 120 In addition, there is in vivo evidence that ALCAR can reverse these membrane molecular and metabolic changes in some AD subjects.…”

Section: Restoration Of Cell Membranesmentioning

confidence: 99%

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

2000

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Acetyl-L-carnitine (ALCAR) contains carnitine and acetyl moieties, both of which have neurobiological properties. Carnitine is important in the ␤-oxidation of fatty acids and the acetyl moiety can be used to maintain acetyl-CoA levels. Other reported neurobiological effects of ALCAR include modulation of: (1) brain energy and phospholipid metabolism; (2) cellular macromolecules, including neurotrophic factors and neurohormones; (3) synaptic morphology; and (4) synaptic transmission of multiple neurotransmitters. Potential molecular mechanisms of ALCAR activity include: (1) acetylation of -NH 2 and -OH functional groups in amino acids and N terminal amino acids in peptides and proteins resulting in modification of their structure, dynamics, function and turnover; and (2) acting as a molecular chaperone to larger molecules resulting in a change in the structure, molecular dynamics, and function of the larger molecule. ALCAR is reported in double-blind controlled studies to have beneficial effects in major depressive disorders and Alzheimer's disease (AD), both of which are highly prevalent in the geriatric population. Molecular Psychiatry (2000) 5, 616-632.

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“…Vermeulen et al (1987) showed that in in vivo spectra of human brain the TI relaxation time of the PME peak, which is also known to consist primarily of PE and PC (Pettegrew et al, 1987), is greater than 2 s. It is therefore probable that the much greater relative concentrations of the PME components in the in vitro spectra from each tumour is due to signal suppression, which occurs in vivo as a consequence of the shorter repetition time used for the in vivo measurements. The spectral components in the extracts may also have shorter TI relaxation times than is the case in vivo since the solvent mixture in the aqueous phase contains about 50% methanol.…”

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confidence: 99%

A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism

Smith

Glaholm

Leach³

et al. 1991

Br J Cancer

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Summary An in vivo 31P NMR spectrum was obtained from each of four human breast tumours. The phosphomonoester and phosphodiester region of each spectrum consisted of a broad peak. Chemical extracts from samples of each of the tumours obtained at resection were examined on a high field strength NMR system. The phosphomonoester region in the spectrum from each extract resolved into three peaks consisting of phosphocholine, phosphoethanolamine and a nucleoside monophosphate. The phosphodiester region resolved into two components, glycerophosphorylcholine and glycerophosphorylethanolamine. Comparing the in vivo and in vitro data from each tumour showed that the contribution of phosphodiester was much lower in the in vitro spectra. We believe this to be a consequence of phospholipid, which would not appear in the aqueous extract, contributing to the phosphodiester peak in vivo.The presence of high concentrations of phosphomonoesters (PMEs) in human breast tumours has been demonstrated by several in vitro (Degani et al., 1986;Barzilai et al., 1988;Merchant et al., 1988) and in vivo (Sijens et al., 1988; Glaholm et al., 1989) studies using 31P NMR spectroscopy. Sijens et al. (1988) reported that the positive response of two breast carcinomas to radiotherapy was accompanied by a decrease in the PME content of the tumours. Further, quantitated changes in PME levels have been observed in a patient undergoing endocrine treatment and subsequently chemotherapy for locally advanced breast carcinoma using a whole body 3lP NMR system Glaholm et al. (1989). These findings suggest that the PMEs may be sensitive indicators of tumour cell response to treatment.In vitro studies of chemical extracts from samples of human breast tumours (Merchant et al., 1988) and human cell culture systems (Daly et al., 1987) have suggested that in breast tumours the PMEs consist principally of phosphoethanolamine (PE) with minor contributions from phosphocholine (PC) and several nucleoside monophosphates.In order to assess the extent to which in vitro NMR data are representative of tissue in vivo, and to assist in the interpretation of therapy-induced changes in in vivo spectra, we are comparing high resolution NMR spectra from extracts of human breast tumours with in vivo spectra from the same tumours prior to operation. The present study shows preliminary results from four patients which in three cases are compared with an assessment of necrotic fraction.In vivo measurements were performed using a 1. (Graham et al., 1987). D20 (final concentration 10%) and methylene diphosphonic acid (2.5 gmoles) were added to the aqueous phase of the extract and the pH was adjusted to 7.4. NMR analysis of the aqueous extracts was carried out on a Bruker Spectrospin AC250 spectrometer operating at 101 MHz (for 31P). All measurements were performed under proton-decoupled conditions in a 10 mm probe. At least 2,000 acquisitions were obtained from each sample. The parameters used for each acquisition were: sweep width 7937 Hz; acquisition time 0.5 ms; acquisition ...

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31P Nuclear Magnetic Resonance Studies of Phosphoglyceride Metabolism in Developing and Degenerating Brain

Cited by 154 publications

References 0 publications

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism

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