Microbial Pathways of Lipid A Biosynthesis
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
As shown in Figure 2, a portion of the lipid A moieties found in wild-type E. coli K-12 may be substituted with a pyrophosphate residue at position 1 rather than with the more abundant monophosphate (111). The origin of this pyrophosphate is unknown. Recent studies in mutants with reduced levels of the MsbA protein (125) (an ABC transporter involved in lipid A transfer across the inner membrane) suggest that the formation of the pyrophosphate occurs in conjunction with transport (126). When MsbA levels are low, hexa-acylated lipid A moieties on nascent LPS accumulate in the inner membrane, but only the monophosphate form is present (126). If the extra phosphate is indeed added on the periplasmic surface of the inner membrane or in the outer membrane, then ATP is unlikely to be the phosphate donor. Other high-energy compounds, such as bactroprenyl pyrophosphate (3) or diacylgycerol pyrophosphate (129), would have to be considered, since they are more likely to gain access to the outer layers of the cell envelope.
The Scientific Basis of Urinary Stone Formation
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Urinary tract infections involving urea-splitting organisms often lead to the formation of stones that consist of calcium phosphate often mixed with magnesium ammonium phosphate (92). Chemically, the process involves the breakdown of urea by the enzyme urease to form ammonium, bicarbonate and hydroxyl ions (Fig. 15) with an accompanying marked alkalinization of urine (pH > 7.2). Under these conditions, the supersaturation of urine with respect to both calcium phosphate and magnesium ammonium phosphate reaches values that cause spontaneous precipitation of these salts and massive crystalluria (Fig. 16) (92,93). In addition, two of the known inhibitors of calcium phosphate crystal growth, pyrophosphate and citrate, are often low in the urines of patients with urinary tract infections, and this may allow the formation of larger than normal crystals and aggregates of calcium phosphate, thereby increasing the risk of stone formation (8). A list of the organisms causing urinary tract infection and their ability to produce urease is contained in Table 4. The risk factor model of infected stone formation is shown in Figure 17.
The parathyroid glands
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
In patients with advanced malignancy and a serum calcium level >3 mmol/L, agents that blunt the release of calcium from skeletal stores may be required. First-line treatment includes administration of bisphosphonates. These are pyrophosphate analogues that inhibit osteoclast activity in areas of high bone turnover. In the acute setting, these are given intravenously due to poor absorption in the gastrointestinal tract. Calcitonin can be used to both decrease osteoclastic activity and increase renal excretion of calcium. It has a short duration of action and is usually used as a bridge to reduce calcium until the sustained action of the bisphosphonates is seen. Finally, glucocorticoids (prednisolone) can be used to enhance the action of calcitonin. They increase calciuresis and decrease intestinal absorption of calcium. As a result, they may also play a role in diseases associated with vitamin D excess.
Experimental study on preparation and anti-tumor efficiency of nanoparticles targeting M2 macrophages
Published in Drug Delivery, 2021
Zheng Zeng, Yu Liu, Qinglian Wen, Yixian Li, Jing Yu, Qiang Xu, Wenwu Wan, Yu He, Chen Ma, Yan Huang, Helin Yang, Ou Jiang, Fuyu Li
Imidazole group can aggregate isopentene pyrophosphate by inhibiting -ferric pyrophosphate synthase and thereby it can lead to cell apoptosis (Gu et al., 2015). Imidazole-based drugs possess remarkable anticancer activities, due to their ability to hinder cell growth and cell division. It is an important part of the molecular structure of many drugs including anti-tumor drugs, dacarbazine, temozolomide, zoledronic acid, mercaptopurine, nilotinib, tipifarnib, etc., which has been reported for the effect of cytotoxicity and anti-cancer properties (Ali et al., 2017). As a kind of synthetic pyrophosphate in which the basic molecular structure is ‘P-C-P’, etidronic acid cannot be metabolized by biological cell and then accumulate in the cell after entering cell. Pyrophosphate can inhibit the activity of some enzymes of cells, especially farnesyl pyrophosphate synthase, and lead to cell apoptosis (Brown & Holen, 2009).
Diagnosis and management of systemic sclerosis-related calcinosis
Published in Expert Review of Clinical Immunology, 2023
Michael Hughes, Ariane L Herrick
The remit of this review is to discuss diagnosis and management. Discussion of pathogenesis is therefore outside its scope. Nonetheless, it is worth mentioning that after decades of very little interest in SSc-related calcinosis, progress is now being made and this includes research into pathophysiology. Increased understanding of the causes and mechanisms of calcinosis will inform development of targeted treatments. SSc-related calcinosis is thought to be dystrophic: it is not related to hypercalcemia (a question often asked by patients, who can be reassured that the presence of calcinosis does not influence the decision as to whether or not they should take calcium supplements). Contributing factors to pathogenesis are likely to include ischemic tissue damage [12,15,22], mechanical pressures [13], and abnormalities of bone matrix proteins [23]. It is possible that the extracellular matrix abnormalities which occur as part of the SSc disease process provide a ‘primed microenvironment’ for soft tissue calcification [24]. Reduced levels of circulating inorganic pyrophosphate (which binds to the surface of hydroxyapatite and inhibits crystal growth) have recently been reported in patients with SSc [25] and might therefore be implicated. As our understanding of pathogenesis increases, so too do the chances of identifying new treatment pathways.
Smartphone technology facilitates point-of-care nucleic acid diagnosis: a beginner’s guide
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Vinoth Kumar Rajendran, Padmavathy Bakthavathsalam, Peter L. Bergquist, Anwar Sunna
A large number of pyrophosphate ions that can chelate metal ions are produced during LAMP-based DNA amplification, leaving the calcein free to emit fluorescence as a proxy for hydrogen ions [117]. Hydrogen ions released during amplification change the pH of the solution, and pH-sensitive dyes like phenol red, neutral red and m-Cresol purple can be used as colorimetric reporters for the detection of PCR [118]. In another approach, oligonucleotides labeled with gold nanoparticles can be added at the end of amplification to produce a visual color change [119]. Colorimetric methods that rely on visual inspection of color change provide a qualitative yes/no result. Smartphone capabilities can be utilized to capture the images in RGB (red, green, blue) format and obtain the pixel intensity of each RGB channel [120]. The intensity analysis allows better quantitative characterization of the colorimetric signal. The intensity of color change is correlated to the concentration of pathogen using the smartphone image analysis tool. Gold nanoparticle-based colorimetric detection of DNA was achieved using a digital lock-in amplifier within a smartphone [121]. In this approach, the audio jack was used as a detector and drove the laser diode to achieve improved and sensitive detection. Digital lock-in, amplifier-based colorimetric detection had a detection limit of 0.77 nmol of DNA which was 5.7 times better than a laboratory grade ultraviolet-visible spectrophotometer.
Related Knowledge Centers
- Chemistry
- Ester
- Nucleotide
- Phosphate
- Tetrasodium Pyrophosphate
- Phosphorus
- Oxyanion
- Disodium Pyrophosphate
- Organic Acid Anhydride
- Adenosine Triphosphate