Lower-intensity aerobic endurance sports
Nick Draper, Helen Marshall in Exercise Physiology, 2014
The Krebs cycle, also known as the tricarboxylic acid cycle or citric acid cycle, involves nine reactions which occur within the matrix of the mitochondria (see Figure 12.3). Through their respective primary metabolic pathways, carbohydrates and fats are converted to acetyl CoA for entry to the Krebs cycle. Protein, if catabolised for energy production, enters the Krebs cycle at a variety of points according to the structure of its carbon-based skeleton. These entry points for protein are shown in Table 12.1. The Krebs cycle, shown in Figure 12.8, was named after Sir Hans Krebs who first identified the nine reactions in the pathway. This process, as with glycolysis and β oxidation, releases hydrogen atoms for use within the electron transport chain. The Krebs cycle employs both FAD and NAD+ as co-enzyme carriers for the hydrogen atoms removed from substrates. In Figure 12.8 both the reactions and the chemical compositions of the intermediary substrates within the Krebs cycle are illustrated.
Energy depletion
Shaun Phillips in Fatigue in Sport and Exercise, 2015
Approximately 90% of fat stores are in the form of triglycerides in adipose cells located at various sites around the body. However, there is a smaller but important store of intramuscular triglycerides. Adipose and muscle triglycerides can be used for fuel during exercise. Adipose triglyceride stores are broken down via lipolysis, a process regulated by specific hormone-sensitive lipases that yields one glycerol and three fatty acid molecules from each triglyceride molecule. Glycerol and fatty acids move into the blood, where glycerol can be taken up by the liver and used to form triglyceride, be oxidised and enter glycolysis, or converted to glucose. Free-fatty acids (blood-borne fatty acids that are not bound to the plasma protein albumin) can enter the muscle via a family of fatty acid transporter proteins and the protein fatty acid translocase (FAT/CD36). Once inside the muscle cell, fatty acids are converted to acyl-CoA and enter the mitochondria via the carnitine shuttle. Once inside the mitochondria the fatty acids can undergo β-oxidation, whereby carbon units in the form of acetyl-CoA are removed from the fatty acyl-CoA molecule. Two carbon units are removed for each cycle of β-oxidation. These acetyl-CoAs can then enter the Krebs cycle and contribute to aerobic ATP resynthesis. Fat cannot generate ATP anaerobically.
K
Anton Sebastian in A Dictionary of the History of Medicine, 2018
Krebs, Sir Hans Adolf (1900–1982) German-born British biochemist, the discoverer of Krebs cycle, was born in Hildesheim. He assisted Otto Warburg at the Kaiser Wilhelm Institute of Cell Pathology, Berlin. He emigrated to England in 1934 and worked with Frederick Gowland Hopkins on redox reactions. He was made professor of biochemistry at Sheffield in 1945, and later at Oxford in 1954. He first described the urea cycle in which carbon dioxide and ammonia form urea in the presence of liver slices and catalytic amounts of ornithine and citrulline. This led on to his elucidation of the citric acid cycle. He also discovered purine synthesis in birds and utilization of ketone bodies in starved rat heart muscle. Krebs shared the Nobel Prize for Physiology or Medicine with an American biochemist, Fritz Albert Lipman (1899–1986) in 1953.
The ancestral stringent response potentiator, DksA has been adapted throughout Salmonella evolution to orchestrate the expression of metabolic, motility, and virulence pathways
Published in Gut Microbes, 2022
Helit Cohen, Boaz Adani, Emiliano Cohen, Bar Piscon, Shalhevet Azriel, Prerak Desai, Heike Bähre, Michael McClelland, Galia Rahav, Ohad Gal-Mor
Some Enterobacteriaceae species, including S. enterica, are capable of utilizing citrate as a carbon and energy source. Under aerobic conditions, growth on citrate is dependent on an appropriate transport system and a functional tricarboxylic acid (TCA cycle, also known as Krebs or citric acid cycle). Citrate fermentation requires the functional citrate transporter CitT, the citrate lyase (encoded by citCDEFXG), and the two-component regulatory system encoded by citAB.29 RNA-Seq data showed that DksA strongly represses the citrate regulon in S. Typhimurium and also (although to a lesser extent) in S. bongori and E. coli (Figure 3(a)). qRT-PCR analysis confirmed these results and showed that in S. Typhimurium, in the absence of DksA, the expression of citC, citD and citX increased by 6, 2.5, and 3-fold, respectively (Figure 3(b)), indicating that DksA is a negative regulator of the citrate regulon in S. enterica.
The potential for metabolomics in the study and treatment of major depressive disorder and related conditions
Published in Expert Review of Proteomics, 2020
The TCA cycle, also known as the citric acid cycle (CAC), links carbohydrate, fat, and protein metabolism and represents the most important pathway for releasing energy in the human body. A study conducted an LC-MS based metabolomic analysis of plasma samples from MDD patients, from three independent clinical centers. In total, five metabolites were associated with the severity of depression, including betaine, citrate, 3-hydroxybutyrate (3HB), GABA, and creatinine. In addition, suicidal ideation has been positively correlated with citrate levels and negatively correlated with kynurenine and 3-hydroxykynurenine levels [75]. However, other studies have reported lower levels of citrate in the serum and urine of MDD patients [70,76]. In addition to citrate, reduced levels of hexadecanoic acid, octadecanoic acid, linoleate, pyruvic acid, and oxoglutaric acid, which are associated with the tricarboxylic acid (TCA) cycle, were observed in plasma and urine samples from adrenocorticotrophic hormone-induced and CUMS-induced animal models of depression [68,70,77]. The creatine-phosphocreatine system plays an important role in cellular energy transportation. Creatine levels have been shown to be reduced in both plasma and urine samples from MDD patients [28,78]. These observed alterations in TCA cycle metabolites and cellular energy-transportation provide new evidence for the contributions of energy metabolism disruptions to MDD; however, the underlying mechanisms associated with these disruptions and the extrapolation of animal model results to humans require further research.
Prospects of biological and synthetic pharmacotherapies for glioblastoma
Published in Expert Opinion on Biological Therapy, 2020
David B. Altshuler, Padma Kadiyala, Felipe J. Nuñez, Fernando M. Nuñez, Stephen Carney, Mahmoud S. Alghamri, Maria B. Garcia-Fabiani, Antonela S. Asad, Alejandro J. Nicola Candia, Marianela Candolfi, Joerg Lahann, James J. Moon, Anna Schwendeman, Pedro R. Lowenstein, Maria G. Castro
IDH1 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) [86]. α-KG is a key metabolite involved in the Krebs cycle. It is also important for the activity of α-KG dependent enzymes including the DNA hydroxylase ten-eleven translocation (TET) enzymes and histone demethylases (KDM) enzymes [87]. As described, mutation in IDH1 (IDH1-R132H) is a hallmark genetic marker in a subset of gliomas [12]. This mutation generates a gain of function in IDH1 enzymatic activity, producing 2-hydroxyglutarate (2-HG) from α-KG [12]. 2-HG is an ‘oncometabolite’ which acts as a competitive inhibitor to α-KG. This alters the glioma cell metabolism and impairs the activity of α-KG dependent demethylases, resulting in hypermethylation of DNA and histones [88]. As a consequence, mutant IDH1 glioma cells exhibit metabolic and epigenetic reprogramming that impacts tumor development and cellular signaling [89]. Glioma patients harboring IDH1-R132H are younger at the time of diagnosis and have a better prognosis compared with wild-type DH1 glioma patients [7,14]. Despite this relative survival benefit, gliomas with IDH1-R132H are invasive and can progress to grade IV [90]. The molecular mechanisms contributing to the increased median survival in IDH1-R132H tumors are not completely understood. The mechanisms are likely closely related to the epigenetic changes in gene expression induced by mutant IDH1 activity. It has been reported that mutant IDH1 blocks cell differentiation [91,92] and inhibition of 2-HG production decreases cell proliferation, delaying growth of mutant IDH1 expressing xenografts [93].
Related Knowledge Centers
- Anaerobic Respiration
- Cellular Respiration
- Chemical Reaction
- Fermentation
- Precursor
- Protein
- Carbohydrate
- Redox
- Acetyl-Coa
- Fat