Alzheimer’s disease and total plasma aminothiols

McCaddon, Andrew; Hudson, Peter; Hill, Diane; Barber, Joan; Lloyd, Alwyn; Davies, Gareth; Regland, Björn

doi:10.1016/s0006-3223(02)01451-8

Cited by 81 publications

(50 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Methionine and homocysteine were not shown to be substrates for CDO, however the latter inhibited CDO activity suggesting that homocysteine may have a direct impact on cysteine metabolism. High levels of homocysteine together with elevated amounts of cysteine have been observed in diseases such as in Alzheimer disease (36), raising the possibility that the increase in cysteine levels is a result of CDO inhibition by homocysteine.…”

Section: Fig 5 Cdo Inhibition By Homocysteinementioning

confidence: 99%

Heterologous Expression, Purification, and Characterization of Recombinant Rat Cysteine Dioxygenase

Chai

Jerkins

Banik

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cysteine dioxygenase (CDO, EC 1.13.11.20) catalyzes the oxidation of cysteine to cysteine sulfinic acid, which is the first major step in cysteine catabolism in mammalian tissues. Rat liver CDO was cloned and expressed in Escherichia coli as a 26.8-kDa N-terminal fusion protein bearing a polyhistidine tag. Purification by immobilized metal affinity chromatography yielded homogeneous protein, which was catalytically active even in the absence of the secondary protein-A, which has been reported to be essential for activity in partially purified native preparations. As compared with those existing purification protocols for native CDO, the milder conditions used in the isolation of the recombinant CDO allowed a more controlled study of the properties and activity of CDO, clarifying conflicting findings in the literature. Apo-protein was inactive in catalysis and was only activated by iron. Metal analysis of purified recombinant protein indicated that only 10% of the protein contained iron and that the iron was loosely bound to the protein. Kinetic studies showed that the recombinant enzyme displayed a K m value of 2.5 ؎ 0.4 mM at pH 7.5 and 37°C. The enzyme was shown to be specific for L-cysteine oxidation, whereas homocysteine inhibited CDO activity.

show abstract

Section: Fig 5 Cdo Inhibition By Homocysteinementioning

confidence: 99%

Heterologous Expression, Purification, and Characterization of Recombinant Rat Cysteine Dioxygenase

Chai

Jerkins

Banik

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Being SAH a strong competitive inhibitor of SAM-dependent methyltransferases, involved in methylation of DNA (among others substrates) and gene expression regulation, SAH accumulation can induce hypomethylation, by decreasing SAM/SAH ratio (methylation potential; MP), and deregulation of gene expression [46][47]. Furthermore, the alteration of GSH metabolism derived from transsulfuration pathway impairment suggests that hypomethylation, together with the alteration of the redox homeostasis, is a mechanism through which one-carbon metabolism alteration is involved in brain diseases [46,[48][49].…”

Section: Sam Metabolismmentioning

confidence: 99%

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Cavallaro¹,

Fuso²,

D’Erme³

et al. 2016

Int J Clin Nutr Diet

View full text Add to dashboard Cite

S-adenosyl-L-methionine (SAM) is the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. SAM level in the organism decreases with aging and restoring the original levels through exogenous supplementation is an important tool for the improvement of many vital functions. Indeed, SAM deficiency may contribute to the onset of several diseases, i.e. depression, liver diseases, osteoarthritis and senile neurological disorders such as Alzheimer's and Parkinson's diseases. Recent evidences indicate that SAM may have an involvement in oxidative stress, a process which typically involves an alteration of cellular sulfur amino acids homeostasis. SAM is not only the principal methyl donor, but also a precursor of glutathione, the major endogenous antioxidant, whose role in counteracting oxidative stress is well known. In this review we will highlight the role of SAM not just as a methyl-donor but also as a regulator of different metabolic pathways involved in the antioxidant response in brain related disorders. Role of S-adenosylmethionine in the Modulation of Oxidative StressRelated Neurodegeneration Review ArticleOpen Access IntroductionThe interaction between environmental and genetic factors plays a fundamental role in inducing and modulating the aging processes towards brain disorders. Among environmental factors, diet and nutritional lifestyle have a key role in brain health through the alteration of the intake or the bioavailability of metabolites and cofactors. Specific nutritional factors have particular impact on one-carbon metabolism, which is a complex biochemical pathway regulated by the presence of folate, vitamin B12 and B6 (among other metabolites) and leading to the production of S-adenosyl-L-methionine (SAM), the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. This metabolism involves three interrelated biochemical pathways: folate cycle, transsulfuration pathway and methionine cycle. These three metabolic sequences were first combined and correlated in 1964 by Laster's group [1][2][3] giving the integrated point of view of transmethylation and transsulfuration pathways, linking sulfur amino acid metabolism to the provision of methyl groups for many biochemical processes. Normal functioning of this metabolic cycle is essential for growth and development and impairment of this metabolism; transmethylation efficiency is associated with many diseases like cardiovascular diseases [4][5], liver diseases [6-9], neural tube defects [10] and brain diseases [11][12][13][14][15][16]. One-carbon metabolism alterations, low methylation and oxidative stress are all linked to Late Onset Alzheimer's Disease (LOAD) [17][18][19][20][21][22][23][24] Moreover, wide confirmed reports underline the role of SAM dependent reactions in age related neurodegeneration also showi...

show abstract

“…34 Several studies suggest that elevated tHcy is also a risk factor for leukoencephalopathy, 35 cognitive impairment, [5][6][7] and AD. [8][9][10][11] However, other studies did not detect significant associations with AD or cognitive status, [12][13][14] stressing the need for further careful study.…”

Section: Figure 2 Within Each Diagnostic Group Total Homocysteine (mentioning

confidence: 99%

“…Several groups reported elevated tHcy in AD cases, [8][9][10][11] attributed to relative deficiencies of folate and vitamin B 12 . While we found lower folate levels in our AD cohort, tHcy and vitamin B 12 were not influenced by an AD diagnosis.…”

Section: Figure 2 Within Each Diagnostic Group Total Homocysteine (mentioning

confidence: 99%

See 1 more Smart Citation

Carotid dissection causing occipital lobe infarction

Cucchiara

Kasner

2005

Neurology

View full text Add to dashboard Cite

Abstract-Background: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid ␤ protein (A␤) metabolism, implicated in neurodegenerative diseases. Objective: To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD). Methods: Plasma tHcy, folate, vitamin B 12 , creatinine, and A␤ levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n ϭ 145), MCI (n ϭ 47), PD (n ϭ 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n ϭ 25), and no dementia (n ϭ 88). Results: The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p Ͻ 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p Ͻ 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma A␤ levels even after adjustments for age and creatinine (p Ͻ 0.0001). Conclusions: Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma A␤ levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.

show abstract

Alzheimer’s disease and total plasma aminothiols

Cited by 81 publications

References 27 publications

Heterologous Expression, Purification, and Characterization of Recombinant Rat Cysteine Dioxygenase

Heterologous Expression, Purification, and Characterization of Recombinant Rat Cysteine Dioxygenase

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Carotid dissection causing occipital lobe infarction

Contact Info

Product

Resources

About