Triglycerides are a main source of energy for humans, which are storage molecules composed of fatty acids that may undergo fatty acid beta-oxidation when in need of energy (D. R. de Assis et al, 2003). Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) is the most commonly diagnosed mitochondrial fatty acid β-oxidation disorder that prevents fatty acid conversion to energy (Rinaldo et al., 2002). MCAD deficiency is caused by mutations in the gene coding for the MCAD enzyme, and the disorder occurs in 1 of every 17,000 people, with the highest frequency in Northern European populations (Kompare & Rizzo, 2008; Rinaldo et al., 2002). Individuals are often diagnosed using genetic and molecular testing by looking at DNA, as well as the contents of urine samples (Matern & Rinaldo, 2012 ). Newborn screening may help identify affected individuals before the onset of symptoms and take preventative measures against this disorder (Kompare & Rizzo, 2008). MCAD normally metabolizes medium-chain acyl-CoAs in the matrix of the mitochondria. In fatty acid β-oxidation, MCAD catalyzes the dehydrogenation of acyl-CoAs with four to 12 carbons in chain length (Matern & Rinaldo, 2012). In MCAD deficiency, this initial dehydrogenation step of the beta-oxidation process if significantly hindered, resulting in ineffective fatty acid degradation. A deficiency in the MCAD enzyme is caused by premature degradation due to an accumulation of improperly folded proteins and tetramer assembly. Beta-oxidation is severely impacted because the enzyme also has reduced enzymatic function due to higher Km values for medium-chain fatty acid substrates and lower affinity for its substrates (Kieweg et al., 1997). Because access of energy via beta-oxidation... ... middle of paper ... ... which is catalyzed by b-ketoacyl CoA thiolase. The products are acetyl-CoA and a long chain fatty acyl CoA that is 2 carbons shorter than the original fatty acyl CoA. One complete round of β-oxidation cleaves 2 carbons from the fatty acid chain, and the process continues until the entire fatty acid chain is broken down into acetyl propinoyl CoA. For example, an 18 carbon chain fatty acid would need to go through 9 rounds of β-oxidation in order to be completely metabolized. Thus, a normal ACADM gene will encode for a fully functioning medium-chain specific acyl-Coenzyme A dehydrogenase. In fatty acid β-oxidation, the MCAD enzyme is responsible for catalyzing the initial step of the mitochondrial β-oxidation pathway for medium-chain fatty acids (C6-C12). The initial step is crucial to allow the progresssion of the β-oxidation pathway. MCAD Deficiency and β-oxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism. It most often affects polyunsaturated fatty acids, because they contain multiple double bonds in between which lie methylene bridges (-CH2-) that possess especially reactive hydrogens. As with any radical reaction, the reaction consists of three major steps: initiation, propagation, and termination.
Lipid metabolism is one source of energy for the human body. We eat food containing one form of lipids, triacylglycerols. Before starting lipid metyabolism, these fats get broken down into droplets by bile salts.Triacylglycerols can be broken into fatty acids plus glycerol via hydrolysis with the help of the pancreatic lipase enzymen and then get used by cells for energy by breaking down even further. Once the pancreas and cells have enough energy and don’t need to absorb anymore, fatty acids get synthesized back into triacylgleryols. The excess triacylglycerols get stored in adipose tissue. Excess storage leads to weight gain and obesity.
Without this enzyme, cells would resort to producing lactic acid in order to obtain ATP, this would ultimately result in acidosis and death. The Citric Acid cycle would cease to function because there would be no ATP present in the mitochondria to support oxidative phosphorylation, which yields the most ATP by converting the NADH and FADH produced in the citric acid cycle to
The active site of the enzyme is present in the α, α’, and α” subunits contained within the αβ-barrels, which ...
Metabolic pathways are a series of reactions catalysed by multiple enzymes. Feedback inhibition, where the end product of the pathway inhibits an earlier step, is an
As we examining a case study about MDCM, which being largest Contract Manufacturer for Medical devices is suffering from financial loss of $ 33 Million for consecutive Quarter in 2002. CEO McMullen has taken over the command since last 2 years. His strategies to work on operation and cost improvements have not been effective, so far. He still has a year ahead to implement and make improvements in his plan.
Aconitase catalyzes the conversion of citrate to isocitrate in the mitochondria and cytosol. In the mitochondria, aconitase is required for the TCA cycle to continue. In the case of high mitochondrial ROS production, aconitase becomes oxidized and no longer functions...
BAT functions in heat production through thermogenesis. WAT comprises the majority of adipose found in adults. WAT adipocytes store fatty acids (FA) esterified with glycerol in the form of triacylglycerols (TAG). Circulating FAs are attached to lipoproteins are transported into adipocytes via lipoprotein lipase. Glucose and other non-lipid entities may be converted into lipids via lipogenesis within adipocytes. Adipocytes also serve an endocrine function secreting adipocytokines such as adiponectin, leptin and resistin [1].
Many factors, for example, pH and temperature affects the way enzymes work by either increasing the rate or determining the type of product produced (). The report, therefore, analyses the effects of the enzyme peroxidase in metabolic reactions and determining its optimum temperature in the reactions.
When animal tissues are facing an anaerobic condition, pyruvate enters fermentation and reduced to lactate. This provides the NAD+ which needed for oxidation of Glyceraldehyde -3-phospahte to run the glycolysis in anaerobic conditions. The above reaction strongly favor lactate formation because standard –free energy is large and negative (ΔG’0= -25.1 kJ/mol) ( Lehniger ).Although LDH is found everywhere and perform the same function in all living system, its polypeptide subunits are different in each part of the body. LDH is first perfect example of an isoenzyme found in history ( ).In this lab, we will be purifying M4 type pyruvate which has four identical subunits. This type of LDH is predominately found in muscle. The LDH is also involved in Cori Cycle (reverse reaction) and pyruvate to lactate conversion in aerobic condition such as erythrocytes which cannot do oxidative respiration because of lack of
Metabolic Syndrome (syndrome X, insulin resistance syndrome) is the name for a group of risk factors that raises your risk for diabetes mellitus (DM), cardiovascular disease (CVD), and other health problems, such as diabetes and stroke.2 It is characterized by abdominal obesity, insulin resistance, hypertension, low HDL, and elevated triglycerides. Some hallmarks of metabolic syndromes are dyslipidemia, central adiposity, and a predisposition to atherosclerotic cardiovascular disease, certain cancers, hypertension, and type 2 diabetes mellitus. Genetics appears to play an important role in predisposing certain individuals and populations to the development of metabolic syndrome.1 Multiple environmental factors modify this genetic predisposition and include physical inactivity, advancing age, cigarette smoking, and endocrine dysfunction. The presence of one or either of these signs should alert the clinician to search for other biochemical abnormalities that may be associated with the metabolic syndrome.
L-Acetylcarnitine, also named as ALCAR, an acetylated form of L-carnitine, fosters the uptake of acetyl coenzyme A (CoA) into mitochondria during fatty acid oxidation, raises the production of acetylcholine, and triggers the synthesis of membrane phospholipid and protein. ALCAR has been explored for use as an acetylcholine mimic as well as in targeting cardiovascular pathologies. Acetyl CoA, as the primary substrate for the Krebs cycle in mitochondria, must be re-charged with an acetyl-group in order for the Krebs cycle to maintain working when it is de-acetylated.
...apter 362. Glycogen Storage Diseases and Other Inherited Disorders of Carbohydrate Metabolism. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved January 21, 2012 from http://www.accessmedicine.com/content.aspx?aID=9144477.
Ketone body is generated from fatty acids at the mitochondria in the liver when glycogen is depleted in the cells. First of all, β-adrenergic catecholamines activates lipolysis to supply fatty acids from adipose tissue during prolonged fasting or low plasma insulin level. Adiposities releases fatty acids into blood by hormone-sensitive lipase. Secondly, fatty acids are formed into long-chain fatty acyl CoA by synthase of fatty acyl CoA. Thirdly, CPT 1 (carnitine palmityl transferase I) catalyses the fatty acyl CoA to carnitine for the purpose ...
2). The cycle is broken into eight consecutive stages (Table 1). The first step initiating the cycle involves acetyl CoA reacting with oxaloacetate to first produce citryl CoA and then citrate from further hydrolysis. In the second step, citrate is isomerised into isocitrate. This is achieved through a dehydration and hydration step with cis-Aconistase produced as an intermediate and the aconitase catalysing the overall reaction. The third step involves isocitrate undergoing decarboxylation and oxidation reactions to form alpha-ketoglutarate (Berg J.M et al., 2015). In step four, a second decarboxylation oxidation reaction occurs to form succinyl CoA from alpha-ketoglutarate. Step five involves splitting succinyl CoA to produce succinate and CoA. In step six, succinate is oxidised to fumurate and FADH2 is formed simultaneously (Ness B., 2017). The penultimate step involves fumurate being converted to malate. In the affixing step of the citric acid cycle, malate is oxidised to form oxaloacetate, enabling a cycle to be established (Berg J.M et al., 2015).