Mechanisms of Synthesis of Adenosine Triphosphate

Racker, Efraim

doi:10.1002/9780470122686.ch7

Cited by 39 publications

(5 citation statements)

References 308 publications

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“…50-fold lower than blood glucose concentration in a healthy person [ 36 , 37 ]. Ribose metabolites contribute to the formation of many important biomolecules such as nucleic acids (RNA and DNA) [ 38 ], vitamins (riboflavin) [ 39 ] and the key energy storing compound, adenosine triphosphate (ATP) [ 40 ]. Most studies focus on the intracellular synthesis of ribose-5-phosphate from glucose [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

2015

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To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs) at the levels that corresponded to approx. 25–30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation) or ribose (ribosylation). Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN) in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women). More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples). Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar supplementation in food and drinks.

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Section: Introductionmentioning

confidence: 99%

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

2015

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“…5, 6 However, as a reducing monosaccharide, Rib has the ability to react with proteins and produce glycated derivatives. In fact previous studies from our laboratory have demonstrated that Rib glycates proteins and gives rise to AGEs more rapidly than Glc in vitro , 7, 8, 9 and that Rib enhances the level of AGEs in cultured human kidney 293 (HEK293T) cells, human neuroblastoma SH-SY5Y cells, and primary cultured hippocampal neurons, leading to reduced cell viability.…”

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confidence: 99%

D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation

et al. 2014

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Non-enzymatic glycation of proteins by reducing saccharides for instance D-glucose is an important post-translational modification regulating protein function. Already two centuries ago, D-glucose (Glc) was identified in the urine of diabetic patients. Recently, abnormally high level of D-ribose (Rib) in the urine of type 2 diabetics has been discovered, which is highly active in protein glycation, resulting in the production of advanced glycation end products (AGEs). Accumulation of AGEs leads to altered cellular function, for example AGE accumulation in the nervous system impairs cognitive ability, yet the mechanisms mediating this process for Rib are unknown. Here we found that treatment with Rib accelerated AGE formation in U251 and U87MG astrocytoma cells and in mouse brain, inducing upregulation of receptor for AGEs (RAGE). Astrocytoma cells with elevated levels of RAGE displayed enhanced activity of the proinflammatory nuclear transcription factor kappaB and increased expression of tumor necrosis factor alpha and glial fibrillary acidic protein. Moreover, injection of Rib induced astrocyte activation in mouse hippocampus and impaired spatial learning and memory abilities. These results indicate that mouse spatial cognitive impairment caused by Rib-derived AGEs is correlated with activation of an astrocyte-mediated, RAGE-dependent inflammatory response. This study may provide insights into the mechanism of Rib-involved cognitive impairments and diabetic encephalopathy.

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“…Tissue hypoperfusion may occur due to low flow CPB hypothermia extreme hemoglobin and excessive neurohormonal activation. This leads to an anaerobic condition in which oxidative phosphorylation is not possible and ATP is produced from pyruvate (18). Few studies have shown that patient's complications and sequel heart valve disease such as breathlessness is a major symptom of heart valve disease, along with swelling of the ankles.…”

Section: Discussionmentioning

confidence: 99%

Defect in mitochondrial functions in damaged human mitral valve

Shinde

Kumar

Mishra³

et al. 2006

Indian J Clin Biochem

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Mitochondrial diseases are a heterogeneous group of disorders in which a primary mitochondrial dysfunction is proven by morphological, biochemical, and genetic examinations. The mitral valve has important function in the regulation of blood flow from one chamber to another. Often, the mitral valve becomes abnormal with age, in Rheumatic fever or it is abnormal from birth (Congenital) or it can be destroyed by infection i.e. bacterial endocarditis and needs replacement. Myocardial function depends on energy produced by mitochondria and in any of these disease conditions, mitochondrial functions and enzyme activities may be impaired. With this in view, we analyzed the relationship between preoperative clinical conditions (as per New York heart Association) and extent of mitochondrial enzyme activities in damaged Human mitral valve in two types of heart disease such as Rheumatic Heart Disease (RHD) and Bacterial Endocarditis (BE). Thirty nine Patients undergoing cardiopulmonary bypass (CPB) for routine valvular heart surgery were included in the study. Controls included 11 normal porcine mitral valve samples without any evidence of heart disease. Mitochondrial enzymes like cytochrome oxidase (COX), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), citrate synthase (CS) and ATPase were determined. Mitochondrial COX, SDH, CS and Total ATPase activities were significantly decreased in disease condition like BE and RHD when compared with control (P<0.001). On the other hand as per New York Heart Association (NYHA) preoperative clinical classification, all the mitochondrial enzymes were significantly (p<0.05) impaired in class IV as compared with NYHA class I, II and III. Present study shows that impairment in the mitochondrial enzymes activities are more pronounced in bacterial endocarditis (BE). It also indicates that damage to mitochondrial enzymes are most pronounced in NYHA class IV.

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Mechanisms of Synthesis of Adenosine Triphosphate

Cited by 39 publications

References 308 publications

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

D-ribosylation induces cognitive impairment through RAGE-dependent astrocytic inflammation

Defect in mitochondrial functions in damaged human mitral valve

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