Cerebrovascular Disease
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
The brain is a highly metabolically active organ and even though it accounts for only 2 per cent of body weight, it uses 20 per cent of cardiac output when the body is at rest. Brain energy use is also dependent on the degree of neuronal activation. The brain uses glucose exclusively as a substrate for energy metabolism by oxidation to carbon dioxide and water. This metabolism allows conversion of adenosine diphosphate to adenosine triphosphate (ATP). A constant supply of ATP is essential for neuronal integrity and this process is much more efficient in the presence of oxygen. Although ATP can be formed by anaerobic glycolysis, the energy yielded by this pathway is small and also leads to the accumulation of toxic lactic acid. The brain needs and uses approximately 500 mL of oxygen and 100 mg of glucose each minute, hence the need for a rich supply of oxygenated blood containing glucose. Mean cerebral blood flow (CBF) in the cortex is normally approximately 50 mL/100 g per minute. The cerebral circulation maintains constant levels of CBF in the face of changing systemic blood pressure by a sophisticated process termed ‘autoregulation’. However, autoregulation has upper and lower limits and in health CBF remains relatively constant over a range of mean arterial blood pressure of between 50 and 150 mmHg. The limits of autoregulation are shifted to higher values in patients with chronic uncontrolled hypertension.
General concepts for applied exercise physiology
Nick Draper, Helen Marshall in Exercise Physiology, 2014
ATP is most commonly catabolised such that one phosphoryl group (also referred to as a phosphate group in some textbooks) is removed and, in the process, energy is released which can be used to perform work. This reaction converts ATP to adenosine diphosphate (ADP) and a separate phosphoryl group (Pi). A simplified illustration of this reaction is shown in Figure 8.2, with a more complete illustration of this reaction found in Chapter 9. Adenosine diphosphate is also a high-energy compound, but only in sustained high-intensity exercise situations is this compound broken down further. More commonly, ADP is phosphorylated (Pi is bonded to ADP) to synthesise ATP. The pathway through which ADP is converted to ATP depends on the rate at which ATP is required by the body.
Synapses
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
To gain a better understanding of second-messenger systems, it is necessary to review first some biochemistry in order to explain the structure of an important, typical second-messenger cyclic AMP (cAMP) and the guanine-derived phosphates. It should be recalled that two of the basic constituents of nucleic acids are the purine compounds adenine and guanine. When attached to the 1ʹ carbon atom of a ribose sugar molecule (Figure 6.10), they become the nucleosides adenosine and guanosine, respectively. When a single phosphate group is attached to the 5ʹ carbon atom of a ribose sugar molecule, these nucleosides become the nucleotides adenosine monophosphate (AMP) and guanosine monophosphate (GMP), respectively. However, another phosphate group can attach to the first phosphate group to give adenosine diphosphate (ADP) and guanosine diphosphate (GDP), respectively. The attachment of a third phosphate group to the second phosphate group, gives adenosine triphosphate (ATP) and guanosine triphosphate (GTP), respectively.cAMP molecule.
The effects of aspirin and ticagrelor on Toll-like receptor (TLR)-mediated platelet activation: results of a randomized, cross-over trial
Published in Platelets, 2019
Kathryn E Hally, Anne C La Flamme, Scott A Harding, Peter D Larsen
Before and after each antiplatelet drug regimen, blood was collected from a peripheral vein into hirudin-anticoagulated tubes (Dynabyte, Munich, Germany). Platelet aggregation was assessed using a modification of light transmittance aggregometry using a Multiskan GO microplate spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA) to confirm that each antiplatelet drug regimen was having the expected inhibitory effect on platelets. Briefly, blood was centrifuged at 200 × g for 12 min to produce platelet-rich plasma (PRP) and at 1500 × g for 12 min to produce platelet-poor plasma (PPP), and warmed to 37°C. Adenosine diphosphate (ADP; 6 µM) or arachidonic acid (AA; 500 µM) was added to PRP. ADP is an agonist for the P2Y12 receptor, which is inhibited by ticagrelor, and AA is an agonist for the cyclooxygenase (COX)-1 receptor, which is inhibited by aspirin. Phosphate-buffered saline (PBS; 145 mM NaCl, 8.7 mM Na2HPO4, 1.3 mM NaH2PO4) was added, in an equal ratio, to warmed PPP. The absorbance was read at 620 nm at 0 min and at 8 min, and all samples were shaken constantly between reads. Maximum platelet aggregation was then calculated.
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Anas Najjar, Rafik Karaman
Platelet aggregation inhibitors are crucial to the management of clotting disorders and to the prevention and follow-up treatment of strokes and cardiovascular incidents. Clopidogrel [22], prasugrel [23], and dabigatran etexilate are prodrugs amongst the most prescribed agents in this class. Clopidogrel and prasugrel are adenosine diphosphate (ADP) receptor blockers while dabigatran etexilate is a direct thrombin inhibitor. Clopidogrel is activated by two-step CYP450 metabolism to furnish its active form. Similarly, prasugrel is hydrolysed by human carboxylesterase 2 (hCE2) to R-95913 and then metabolized to yield R-138727, the active form [24]. Ticlopidine is another prodrug in this therapeutic group. It is an older agent that also inhibits adenosine diphosphate receptors. Though, its use in the daily treatment is limited due to serious side effects such as neutropenia and thrombotic thrombocytopenic purpura.
Evaluation of platelet distribution width in hypertension with hyperhomocysteinemia
Published in Clinical and Experimental Hypertension, 2020
Gang Li, Yanyan Zhang, Zhongwei Zhu, Juan Du
The correlation between PDW and hypertension with HHcy may be because both homocysteine and hypertension can induce platelet activation. Studies in vivo have found that homocysteine can induce an elevation of local adenosine diphosphate levels via the inhibition of adenosine diphosphate hydrolysis, which then stimulates platelet activation (20), and homocysteine can also have the capability of raising the concentrations of arachidonic acid (a platelet agonist) (21). Homocysteine has been observed to increase platelet aggregation and adhesion when induced by thrombin in vitro (22). Subjects with HHcy displayed a higher level of activation of the platelet specific integrinαIIbβ3 (23). Except for direct stimulation, the damage on the blood vessel endothelium via hypertension and homocysteine, and the consequent acceleration of platelet aggregation and adhesion, may be another pathway in promoting platelet activation (14).
Related Knowledge Centers
- Adenine
- Adenosine Monophosphate
- Atpase
- Dephosphorylation
- Organic Compound
- Phosphate
- Metabolism
- Cell
- Sugar
- Adenosine Triphosphate