Cellular Respiration PDF

# Unit VI: Cellular Respiration We need to breathe principally because our cells require $O_2$ to generate adequate amounts of ATP from the oxidation of fuels to $CO_2$ and water. Cellular respiration uses over 90% of the $O_2$ we inhale. ## Phases of cellular respiration ### Phase 1 of cellular r...

# Unit VI: Cellular Respiration We need to breathe principally because our cells require $O_2$ to generate adequate amounts of ATP from the oxidation of fuels to $CO_2$ and water. Cellular respiration uses over 90% of the $O_2$ we inhale. ## Phases of cellular respiration ### Phase 1 of cellular respiration (Fig. 6.1) - The pathways for the oxidation of most fuels (glucose, fatty acids, and many amino acids) converge on the generation of acetyl CoA. - The complete oxidation of the acetyl group to $CO_2$ occurs in the tricarboxylic acid (TCA) cycle, which collects the energy mostly as NADH and $FADH_2$. ### Phase 2 of cellular respiration (Fig. 6.1) - The energy derived from fuel oxidation is converted to the high-energy phosphate bonds of ATP by the process of oxidative phosphorylation. - Electrons are transferred from NADH and $FADH_2$ to $O_2$ by the electron transport chain (ETC). These series of reactions are coupled with the synthesis of ATP as will be discussed later. ### Phase 3 of cellular respiration (Fig. 6.2) - The high-energy phosphate bonds of ATP are used for processes such as muscle contraction (mechanical work), maintaining low intracellular $Na^+$ concentrations (transport work), synthesis of larger molecules such as DNA in anabolic pathways (biosynthetic work), or detoxification (biochemical work), and others. - As a consequence of these processes, ATP is either directly or indirectly hydrolysed to ADP and inorganic phosphate ($P_i$), or to AMP and pyrophosphate (PPI). ## Mitochondria is the site for cellular respiration (Fig. 6.3) - As noted above the components of the ETC are located in the inner mitochondrial membrane. - The mitochondrial matrix (the compartment enclosed by the inner mitochondrial membrane) contains, however, almost all of the enzymes for the TCA cycle and oxidation of fatty acids. ## Example of cellular respiration: Oxidative decarboxylation of pyruvate (the end-product of aerobic glycolysis) - Glucose is a universal fuel used to generate ATP in every cell type in the body (Fig. 6.4). ### In glycolysis, 1 mole of glucose is oxidized to 2 moles of pyruvate and - Small amounts of ATP are generated when high-energy metabolic intermediates transfer phosphate to ADP in a process termed substrate-level phosphorylation. - NADH produced from glycolysis is reoxidized via the electron transport chain, and the pyruvate is transported into the mitochondria where it is further oxidized to acetyl CoA which is the major fuel of the TCA cycle. ### In anaerobic glycolysis - NADH is reoxidized by conversion of pyruvate to lactate, which enters the blood. - Although anaerobic glycolysis has a low ATP yield, it is important for tissues that lack of mitochondria (e.g., R.B.Cs, kidney medulla), or tissues experiencing diminished blood flow (exercising muscle). ## Fate of the end products of aerobic glycolysis (pyruvate and NADH) ### i. Pyruvate - In presence of $O_2$ and mitochondria, pyruvate is transported to mitochondria and undergoes oxidative decarboxylation to acetyl CoA (discussed later). ### ii. Cytosolic NADH: - NADH produced in the cytosol cannot directly pass through the inner mitochondrial membrane to reach the electron transport chain. - NADH is indirectly transferred to the inside of the mitochondria by what is called the shuttle mechanisms (malate aspartate shuttle and glycerophosphate shuttle). - Many tissues contain both the glycerophosphate shuttle and the malate aspartate shuttle. ## Malate-aspartate shuttle (Malate shuttle); Fig. 6.5 - The cytosolic malate dehydrogenase enzyme (MDH) transfers electrons from NADH to cytosolic oxaloacetate to form malate. - Then, Malate is transported across the inner mitochondrial membrane by a specific translocase. - In the mitochondrial matrix, malate is oxidized back to oxaloacetate by mitochondrial malate dehydrogenase, and NADH is generated. This NADH can donate electrons to the electron transport chain with generation of approximately 3 moles of ATP per mole of NADH. - The newly formed oxaloacetate cannot pass back through the inner mitochondrial membrane under physiologic conditions. Therefore, oxaloacetate is converted by Aspartate aminotransferase enzyme (AST) into aspartate. Aspartate is, then, transported out to the cytosol using an aspartate/glutamate exchange translocase. ## Glycerolphosphate shuttle (Fig. 6.6) - The glycerolphosphate shuttle is the major shuttle in most tissues. - In this shuttle, cytoplasmic glycerol 3-phosphate dehydrogenase enzyme transfers electrons from NADH to Dihydroxyacetone phosphate (DHAP) to form glycerol 3-phosphate - Glycerol 3-phosphate then diffuses to the inner mitochondrial membrane, where the electrons are donated to FAD forming $FADH_2$. - $FADH_2$ by using the ETC results in the synthesis of approximately 2 ATP. - Dihydroxyacetone phosphate returns to the cytosol to continue the shuttle.