Cardiac Substrate Metabolism Lab Report

The pyruvate is then imported in to the mitochondria and then it is metabolized by PDC to make acetyl CoA. The acetyl CoA is combined with oxaloacetate by citrate synthase to generate citrate. Then the citrate is exported in the cytoplasm and then it is split in to acetyl-CoA and oxaloacetate by ATP- citrate lyase. Oxaloacetate would be reduced to malate which is then converted in to pyruvate by the malic enzyme which relases NADPH. The pyruvate is then recycled back in to the mitochondria and it is carboxylated by pyruvate carboxylase to make oxaloacetate and this would drive the citrate

For needed energy, a molecule of glucose is broken down through a process called glycolysis to form 2 ATP’s. The by-product is lactic acid. During intense, anaerobic muscle activity, anaerobic hydrolysis occurs. The Cori Cycle is activated to recycle the accumulated lactic acid back into useable energy. The lactic acid travels through the bloodstream to the oxygen-rich liver and is converted back to glucose by a process called gluconeogenesis. The glucose is then returned to the muscle to resupply it with energy. This conversion process uses up 6 ATP’s to make 2 ATP’s for the muscle to reuse. This creates a net loss of 4 ATP’s. The Cori cycle is meant to be a temporary shift of energy production from the oxygen-depleted muscles to the liver.

Calcium needs to be released first and needs to be obtained in the body in order for the body to carry out its function. Calcium or calcium ion (Ca2+) is stored in the sacroplasmic reticulum (SR) to start contraction for the muscles.11 In the case of the cardiac muscle, it would start contraction through the Sodium-Calcium exchange (NCX) and with limited help of the SR. Sodium ions (Na+) would enter from the dyadic cleft, the space where the cell membrane and SR are in close proximity.11 This would cause Ca2+ to flow out of the cell. In order for Ca2+ to reenter it has to go through Ca2+ channels and so Ca2+ would be released.11 Excitation-contraction coupling relies on the dyadic cleft of Ca2+ to be released. Understanding how NCX works could help provide treatment for HF because the cardiac muscle could be manipulated to contract. It may be possible to remove the NCX because it can cause too much Ca2+ to be stored in the SR and cause arrhythmias and cell death.11 This would lead to a pathway to fixing any heart failure

Background Research: Cellular Respiration is used by the cells to make ATP, by releasing chemical energy from sugars and other carbon based molecules. There are 3 stages to Cellular Respiration, Glycolysis, Krebs Cycle, and the Electron Transport Chain. The inputs of Glycolysis are 2 ATP’s, a Glucose molecule, and a Pyruvate. The inputs for the Krebs Cycle are oxygen, and. In animals, energy is consumed by eating food. In that food they eat, Glucose is found and broken down by the process of cellular respiration, which then converts into energy known as ATP. When there is a lot of ATP and Glucose, the liver converts it into glycogen.

13 Boron, W. F., & Boulpaep, E. L. (2009). Medical physiology: a cellular and molecular approach (2nd ed.). Philadelphia, PA: Saunders/Elsevier.

In order to enter the mitochondria, fatty acids are oxidised to fatty acyl-coA. The breakdown of ATP to AMP and pyrophosphate provides energy for this process. Moreover, fatty acyl-coA cannot pass through the inner mitochondrial membrane. Hence, the enzyme carnitine acyl transferase I replaces the coA with carnitine and then fatty acyl-carnitine passes through the acyl-carnitine I carnitine transporter into the mitochondrial matrix. In the matrix, fatty acyl-coA is regenerated by carnitine acyltransferase II. This allows beta oxidation to occur where fatty acid chains split into several molecules of acetyl-coA, yielding one NADH and one FADH2. This process involves the removal of two carbons from the carboxyl chain leading to a fatty acyl-coA chain two carbons shorter through four reactions. In reaction 1, oxidation dehydrogenation occurs converting fatty acyl-coA to trans-Δ2-enoyl-coA. This is catalyzed by the enzyme acyl-coA-dehydrogenase and electrons are transferred to FAD , reducing it to FADH2. Reaction 2 is catalyzed by enoyl-coA-hydratase, where trans-Δ2-enoyl-coA is hydrated to L-β-hydroxyl-acyl-coA. Reaction 3 is catalysed by β-hydroxyl-coA dehydrogenase, where two electrons are transferred fo NAD+ to form NADH, and β ketoacyl-coA is formed. In reaction 4, thiolytic cleavage causes the two carbons at the

Influx and efflux of calcium regulate the membrane potential of the cell, which in turn regulates the contractility of smooth muscle cells. However, we neglected to link calcium’s role in membrane potential to its effects on potassium channels, one of the focuses of the first paper and the main influence on vasodilation and constriction. Furthermore, although external sources backed up the influence of insulin in activating Ca2+-ATPase as we wrote in our second hypothesis, the new supporting information does not mention insulin while suggesting that glucose might have a role in be inhibiting these Ca+-dependent K+

The different types of metabolic reactions that were used to identify the Gram-negative unknown were citrate (CIT), gelatin (GEL), hydrogen sulfide (H2S), tryptophan deaminase (TDA), urease (URE) and Voges Proskauer (VP). In the CIT reaction the capability of using citrate as a carbon source for energy is dependent upon the presence of a citrate permease that facilitates the transport of citrate into the cell. Citrate is then acted upon by citrate, producing oxaloacetic acid and acetate that are converted to pyruvic acid and carbon dioxide. This produced carbon dioxide combines with sodium and water to form sodium carbonate, changing the bromothymol blue indicator that is incorporated into the medium. The citrate-positive cultures are identified by the presence of growth on the surface of the slant and blue coloration while citrate-negative cultures will show no growth and remain green in coloration.

In diabetes type 1, there is a absence of insulin that is needed for glucose to enter a cell to undergo glycolysis. With insulin no longer present, the process of beta oxidation of fatty acids from the adipose tissue starts and converts the fatty acids into the ketones acetoacetate and b-hydroxybutyrate (Tidy, 2016). However, ketones are

Although we might not always acknowledge this small proteins, enzymes have come to be revolutionary when it comes to our survival. This is because enzymes are an example of catalysts, which affect the rate at which a chemical reaction occurs by speeding up. Moreover, this is imperative for our survival because chemical reactions provide the energy required by our bodies to perform several life processes that allow us to carry out many of the activities we perform as part of our everyday life. Thus, an enzyme's ability to function properly has become a major factor in our body's ability to function properly and maintain homeostasis. Unfavorably, however, there are some factors that can negatively affect an enzyme's ability to

“Ischaemic Heart Disease is the generic designation for a group of closely related syndromes resulting from myocardial ischemia- an imbalance of between the supply (perfusion) and demand of the heart for oxygenated blood” [I] However Ischemia is not only characterised by the insufficiency of oxygen, a lack of available nutrient substrates, and inadequate removal of metabolites also plays a combined role. Ischaemic Heart Disease is caused by a lack of blood flow through the blood vessels, these vessels are also known as Coronary Arteries. The blood vessels transports oxygen directly to the heart, however over time these blood vessels can starting accumulating plague, reducing the flow of oxygenated blood to the heart, isolated hypoxemia. The

highly expression PPAR훼 is associated with impair cardiac muscle and reduce left ventricular ejection fraction (27–29) . Stimulant as retinoic acid (30), glucocorticoids (31), retinoid X receptors (32), exercise training (33) , related receptors alpha (34), AMP-activated protein kinase (34,35), heart shock factor-1 (27) enhance number of PPAR훼 receptors on cardiac cells that lead to increase glucose utilization, storage glucose as glucogen , production free radicals, damage mitochondrial and accumulation lipids in cardiac cell that accompany cardiomyocyte apoptosis and hypertrophy

This complex converts pyruvate to acetyl CoA, which is necessary for the initiation of the Krebs cycle that ultimately leads to adenosine triphosphate (ATP) production. When thiamin is depleted, the conversion of pyruvate to acetyl CoA is blocked, promoting pyruvate accumulation in the cytosol and eventual lactate production (Gunnerson & Harvey, 2016). The anaerobic pathway of converting pyruvate to lactate is inefficient, producing only 2 moles of ATP compared to the 30 moles of ATP produced during aerobic respiration. Additionally, a lack of ATP following thiamin deficiency shifts energy metabolism to fat stores, which produces ketones for the production of acetyl CoA. However, fat stores are eventually depleted in chronic thiamin deficiency (Dinicolantonio et al.,

FAO produces a molecule of acetyl CoA in each oxidation cycle and two after full completed cycles. The resulted acetyl CoA is the major requirement for producing the reduced NADP+ in which the generated acetyl CoA enters the TCA cycle and with the availability of oxaloacetate provides citrate that can be export to the cytoplasm. The citrate then enters two reactions to produce cytosolic NADPH (1,3,12). These reactions include the conversion of malate to pyruvate that is catalyzed by malic enzyme (ME1) and the oxidation of isocitrate to α-ketoglutarate by isocitrate dehydrogenase (IDH1) (1,3,12). The produced cytosolic NADPH from FAO acts to sustain the antioxidant system against oxidative stress and to promote cancer cell survival. For instance, during severe oxidative stress the accumulation of oxygen reactive species (ROS) leads to cell death, cytosolic NADPH counteracts ROS by maintaining the reduced form of glutathione (GSH) thereby promoting cancer cell survival (12). In addition, the produced cytosolic NADPH from FAO targets ROS-induced oxidative damage to prevent disrupting mitochondrial and glycolytic ATP production. For example, in a study using SF188 glioblastoma cells the inhibition of FAO by CPTI inhibitor etomoxir hindered NADPH production and resulted in significantly increased of superoxide level in etomoxir treated cells, ATP depletion, and eventually cell death (12). A

The article cited above was written by authors with affiliations to The Cardiovascular Research Group, and talks about the importance of oxygenating the mitochondria that are affected due to ischemic changes during an Acute MI. The article goes on to discuss the importance of oxygen during acute myocardial infarction, and how reducing ischemia will inadvertently help with reperfusion. This article discusses the benefit of oxygen therapy in acute MI on a more cellular basis, but does not go into length about the affects that oxygen has on a patient’s mortality rate.