Proline Metabolism in Neurological and Psychiatric Disorders

Yao, Yuxiao; Han, Weiping

doi:10.14348/molcells.2022.0115

Cited by 13 publications

(9 citation statements)

References 90 publications

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“…In addition, proline has been reported to stimulate the release of glutamate and glutamine from cultured astrocytes [ 47 ] and to modulate central metabolism by acting on hypothalamic astrocytes [ 48 ]. Proline catabolism is exclusively localized in mitochondria [ 49 ]. Cellular proline catabolism starts with its mitochondrial oxidation to pyrroline-5-carboxylate by the flavin-containing proline dehydrogenase that transfers electrons directly onto ubiquinone in the respiratory chain [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…The concentration of proline in human serum has been reported to be in the higher micromolar range (170 µM [ 61 ], 450 µM [ 62 ]), while only 6 µM proline have been determined for cerebrospinal fluid [ 61 ], suggesting that peripheral proline may be one proline source for astrocytes. Further studies are now required to elucidate in detail the proline metabolism of astrocytes and of other brain cells, especially considering that proline has well known behavioral and neurochemical effects [ 63 ] and that the proline metabolism is strongly connected to neurological and psychiatric disorders [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

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Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation

Harders,

Spellerberg,

Dringen

2024

Neurochem Res

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Brain astrocytes are well known for their broad metabolic potential. After glucose deprivation, cultured primary astrocytes maintain a high cellular ATP content for many hours by mobilizing endogenous substrates, but within 24 h the specific cellular ATP content was lowered to around 30% of the initial ATP content. This experimental setting was used to test for the potential of various exogenous substrates to prevent a loss in cellular ATP in glucose deprived astrocytes. The presence of various extracellular monocarboxylates, purine nucleosides or fatty acids prevented the loss of ATP from glucose-deprived astrocytes. Of the 20 proteinogenic amino acids, only alanine, aspartate, glutamate, glutamine, lysine or proline maintained high ATP levels in starved astrocytes. Among these amino acids, proline was found to be the most potent one to prevent the ATP loss. The astrocytic consumption of proline as well as the ability of proline to maintain a high cellular ATP content was prevented in a concentration-dependent manner by the proline dehydrogenase inhibitor tetrahydro-2-furoic acid. Analysis of the concentration-dependencies obtained by considering the different carbon content of the applied substrates revealed that fatty acids and proline are more potent than glucose and monocarboxylates as exogenous substrates to prevent ATP depletion in glucose-deprived astrocytes. These data demonstrate that cultured astrocytes can utilise a wide range of extracellular substrates as fuels to support mitochondrial ATP regeneration and identify proline as potent exogenous substrate for the energy metabolism of starved astrocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation

Harders,

Spellerberg,

Dringen

2024

Neurochem Res

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“…In total, 8 (glutamine, ornithine, aspartic acid, glutamic acid, proline, 4-hydroxyproline, guanidoacetic acid, and GABA) of the 44 metabolites were significantly decreased in arginine and proline metabolism in this study (Table 3). Proline, a non-essential proteinogenic amino acid, plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes [39]. Numerous studies have linked proline metabolism with ROS [40].…”

Section: Discussionmentioning

confidence: 99%

“…Proline synthesis and degradation are both highly redox-active processes [41]. Proline and proline metabolism can act as both ROS scavengers and producers [39]. Consequently, it is critical to balance proline levels and proline metabolic enzyme activities to achieve proline homeostasis for proper cellular functions [39].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Consumption of Purified Water Altered Amino Acid, Fatty Acid and Energy Metabolism in Livers of Rats

Wang,

Qiu,

Zeng

et al. 2024

Metabolites

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The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl–tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention.

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“…Besides, proline metabolism is also related to the changes in ornithine and glutamate; the increased levels of proline were identified in the blood and urine in six studies [63,35,42,65,51,72]. The involved enzymes in proline metabolism, such as P5C reductases (PYCRs) and nicotinamide adenine dinucleotide (NAD)-dependent P5C dehydrogenase (P5CDH), have been reported to play important roles in neuronal function and brain structure, and to be associated with neurodegeneration disorders in several human and animal models [74].…”

Section: Significant Pathways Of Matched Metabolitesmentioning

confidence: 99%

Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

Fleming

Luo

Liu

et al. 2023

Preprint

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Many studies have reported metabolomic analysis of different bio-specimens from Parkinson’s disease patients. However, inconsistencies in reported metabolite concentration changes make it difficult to draw conclusions as to the role of metabolism in the occurrence or development of Parkinson’s disease. We reviewed the literature on metabolomic analysis of Parkinson’s disease patients. From 74 studies that passed quality control metrics, perturbations to 928 metabolites were reported to be associated with PD diagnosis, but only 190 were replicated with the same changing trends in more than one study. Of these metabolites, 60 exclusively increased, such as 3-methoxytyrosine and glycine, 54 exclusively decreased, such as pantothenic acid and caffeine, and 76 inconsistently changed in concentration in PD versus control subjects, such as ornithine and tyrosine. A novel genome-scale metabolic model of PD and corresponding metabolic map linking most of the replicated metabolites enabled a better understanding of the dysfunctional pathways of PD and prediction of additional potential metabolic markers from pathways with consistent metabolite changes to target in future studies.

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Proline Metabolism in Neurological and Psychiatric Disorders

Cited by 13 publications

References 90 publications

Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation

Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation

Long-Term Consumption of Purified Water Altered Amino Acid, Fatty Acid and Energy Metabolism in Livers of Rats

Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

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