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Nutritional Ergogenic Aids: Introduction, Definitions and Regulatory Issues
Published in Ira Wolinsky, Judy A. Driskell, Nutritional Ergogenic Aids, 2004
Ira Wolinsky, Judy A. Driskell
Pyruvate, a ketoacid, is susceptible to acid hydrolysis, with the resultant liberation of carbon dioxide gas. Thus, intuitively, one would expect that at least some of the ingested pyruvate would be degraded within the acidic environment of the stomach. However, this aspect of pyruvate metabolism is generally overlooked. Furthermore, there has been virtually no information to date regarding the efficacy of pyruvate or dihydroxyacetone supplementation. We recently measured whole blood and plasma pyruvate concentrations for a 4-hr period following the acute ingestion a range of oral dosages of pyruvate (7, 15 and 25 g) and found no changes in blood pyruvate levels.14 This strongly suggests that pyruvate is either very poorly absorbed,
Physiological and Pathological Consequences of Streptozotocin Diabetes on the Heart
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Brian Rodrigues, John H. McNeill
In the early stages of diabetes, alterations in both fuel supply and utilization by the heart tissue may be the initiating factor for the development of diabetic cardiomyopathy. Mitochondrial generation of ATP in the heart is through the oxidation of various substrates that include glucose, free fatty acids (FFA), lactate, and ketone bodies.19 The breakdown of glucose or glycogen to pyruvate (glycolysis) provides some energy. However, it is the subsequent entry of pyruvate into the mitochondria and its conversion into acetyl coenzyme A (CoA) that provides the majority of energy obtained from glucose. Acetyl CoA can also be derived from amino acids and FFA. In fact, the heart muscle of rat is known to account for the largest consumption of FFA with respect to body weight.20 The heart has a limited potential to synthesize FFA. Hence, FFA are supplied to cardiac cells from several sources: (1) lipolysis of endogenous triglyceride (TG) within the cardioadipocyte or cardiomyocyte; (2) lipolysis of adipose tissue triglyceride with subsequent entry of FFA into the blood where they are carried to the heart, usually bound to albumin; and (3) lipolysis of circulating triglyceride in chylomicrons and very low density lipoproteins (VLDL) by coronary endothelial-bound lipoprotein lipase (LPL). Vascular endothelial-bound LPL is the rate-limiting enzyme that determines the clearance of plasma TG and partially regulates FFA supply to the tissues; hence, it is also called heparin-releasable “functional” LPL.21 As endothelial cells cannot synthesize LPL, the enzyme is synthesized by the parenchymal cells of a variety of extrahepatic tissues, including adipose, heart, skeletal muscle, brain, and ovary. In the adult heart, LPL is synthesized and processed in myocytes and is translocated onto heparan sulfate proteoglycan (HSPGs) binding sites on the luminal surface of endothelial cells,22 where it actively metabolizes lipoproteins. Chylomicrons and VLDL bind transiently to endothelium-binding lipolysis sites where heparin-releasable endothelial LPL hydrolyzes the TG core to FFA and 2-monoacylglycerol,23 which are then transported into the heart for numerous metabolic and structural tasks.
Pyruvate dehydrogenase complex deficiency mimicking congenital cytomegalovirus infection on imaging
Published in Baylor University Medical Center Proceedings, 2022
Jasmin Rahesh, Rohan Anand, Victor Mendiola, Roy Jacob
The baby was discharged after a 9-day neonatal intensive care unit stay with outpatient follow-up set with a medical geneticist. Blood culture and cerebrospinal fluid culture were negative. Toxo IgM and IgG were negative. A test for cytomegalovirus in the urine was negative. The medical genetic results reported as mosaic for a pathogenic variant in PDHA1 c.904c > T (p.Arg302Cys) and hemizygous for variance of uncertain significance in BOLA3 and SON. Pyruvate acid levels in the blood were elevated at 2.05 mg/dL with a reference range of 0.30 to 1.50 mg/dL. The baby is currently on anticonvulsant therapy due to the development of seizures and remains on a ketogenic diet. He has also presented with gross developmental delay with generalized hypotonia and an inability to sit alone, crawl, or scoot and is enrolled in physical therapy.
Dimensions of inflammation in host defense and diseases
Published in International Reviews of Immunology, 2022
In mammals, lactate is a metabolic by-product of anaerobic respiration, a glycolytic pathway that ensures quick energy replenishment in the form of adenosine triphosphate (ATP) for the cells and prevention of muscle fatigue. Lactate acts as a circulating fuel in the blood that goes to the liver and is converted into pyruvate by the enzyme lactate dehydrogenase. Pyruvate is then converted into glucose via a metabolic pathway known as gluconeogenesis in the liver. Notably, lactate production increases when demand for ATP increases. In the past three decades, lactate has also been proved to be a very important signaling molecule that regulates various signaling pathways including inflammation-associated immune pathways. In this special issue, Zhou et al. [1] and Luo et al. [2] shed light on how endogenous lactate regulates inflammation in various immunological events, such as via macrophage polarization, T-cell immune dysfunction and its link with infectious and noninfectious diseases such as tumors. These two articles will be of interest to a broad readership in the field of immunology, as well as researchers investigating metaflammation and immunometabolic disorders and those in associated fields (Figure 1).
Hepatoprotective effects of ethyl pyruvate against carbon tetrachloride-induced oxidative stress, biochemical and histological alterations in rats
Published in Archives of Physiology and Biochemistry, 2021
Pyruvate (CH3COCOO−), the anionic form of a simple α-keto acid, plays a central role in intermediary metabolism and is the final product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle. Pyruvate probably also functions in cells as an endogenous antioxidant. In aqueous solutions, however, pyruvate is unstable and this certainly limits the therapeutic potential of this compound (Fink 2008). Ethyl pyruvate (EP), a stable and lipophilic derivative of pyruvate, has been shown to have a potent free radical scavenging action in animal models of oxidant-mediated cellular injury (Kao and Fink 2010). Previous studies have revealed that EP shows a potent anti-inflammatory and tissue protection activity in multiple animal models of disease including endotoxaemia (Hauser et al.2005), bacterial sepsis (Zhang et al.2009), acute renal injury (Reade and Fink 2005), acute pancreatitis (Cheng et al.2007), organ ischaemia and reperfusion injury (Tsung et al.2005), haemorrhagic shock (Tawadrous et al.2002), and neuronal injury (Sharma et al.2008). Oxidative stress and apoptosis are considered to play an important role in the development of acute liver injury induced by CCl4, as stated above. Therefore, antioxidant and anti-apoptotic actions may be important in the protection against CCl4-induced liver damage.