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1 Cellular Energy In order to sustain life (steady state), cells constantly expend energy in the form of ATP hydrolysis the hydrolysis of ATP yields a molecule of ADP (adenosine diphosphate) and a Phosphate group ATP ADP + P Following ATP hydrolysis, the cell synthesizes new molecules of ATP using ADP and P ADP + P ATP recycling energy cells use the energy stored in the covalent bonds of monosaccharides, fatty acids and amino acids as an energy source (fuel) to resynthesize ATP

2 Fuels for ATP Synthesis

3 Cellular Respiration Most cells of the body use glucose (in the presence of O 2 that we inhale) as fuel source to synthesize molecules of ATP in a process called cellular respiration The products include molecules of carbon dioxide that we exhale, and water C 6 H 12 O 6 + 6O ADP +38 P 6H 2 O + 6CO ATP note that the number of atoms in the reactants equal the number of atoms in the products

4 Cellular Respiration

5 Cellular Respiration The process of cellular respiration is divided into 3 sequential phases Glycolysis occurs in the cytoplasm of a cell Krebs cycle (Citric acid cycle) occurs in the mitochondrial matrix The electron transport chain occurs across the inner mitochondrial membrane between the mitochondrial matrix and the intermembrane space

6 Cellular Respiration Overview

7 Cellular Respiration During the phases of glycolysis and the Krebs cycle, a single molecule of glucose is gradually broken apart in 20 sequential biochemical reactions into different carbohydrate intermediates only 4 molecules of ATP are synthesized during these phases by the energy released from the breaking of covalent bonds of the carbohydrate intermediates As the glucose molecule is broken apart, the 12 hydrogen atoms are gradually removed and used to create a large H + gradient between the intermembrane space and the matrix of the mitochondria the H + gradient is used as an energy source by the electron transport chain to synthesize the remaining 34 molecules of ATP

8 Glycolysis Overview Glycolysis = sugar breaking The first 7 biochemical reactions of cellular respiration are catalyzed by 7 different enzymes in the cytoplasm Starts with 1 molecule of glucose (6 carbons) and ends with 2 molecules of pyruvic acid (3 carbons x 2 = 6 carbons)

9 Glycolysis During glycolysis: Energy is invested as 2 ATPs are hydrolyzed during steps 1 and 3 One 6 carbon carbohydrate intermediate is split (lysis) into two 3 carbon carbohydrate intermediates during step 4 each of the 3 carbon carbohydrate intermediates molecules lose a H (becoming oxidized) which is accepted by a coenzyme called NAD + (becoming reduced to NADH) during step 5 NADH carries H to the mitochondrial matrix to build the H + gradient 4 molecules of ATP are synthesized 2 during step 6 2 during step 7

10 Glycolysis

11 Products of Glycolysis The products of glycolysis are: 2 molecules of ATP 4 are synthesized, but 2 are hydrolyzed at the beginning of glycolysis 2 molecules of pyruvic acid (3 carbon molecule) 2 molecules of NADH Only 2 of 38 molecules of ATP are synthesized during glycolysis

12 Pyruvic Acid The presence or absence of O 2 in the cell determines how the cell will use the 2 molecules of pyruvic acid at the end of glycolysis If O 2 is present pyruvic acid will be used in the process of aerobic respiration 36 more molecules of ATP are synthesized as cellular respiration continues through the Krebs cycle and the electron transport chain If O 2 is absent the pyruvic acid will be used in the process of anaerobic respiration (fermentation) produces no more ATP

13 Anaerobic Fermentation In the absence of O 2 (oxygen debt), the 2 molecules of pyruvic acid from the end of glycolysis are converted into 2 molecules of lactic acid Anaerobic fermentation most commonly occurs in active skeletal muscle cells when they use O 2 faster than it can be delivered by the respiratory and circulatory systems The accumulation of lactic acid causes: muscle proteins to partially denature leading to muscle weakening (fatigue) muscle soreness

14

15 Aerobic Respiration In the presence of O 2, the 2 molecules of pyruvic acid from the end of glycolysis are transported into the mitochondrial matrix Each molecule of pyruvic acid is then converted into a molecule of Acetyl Coenzyme A (Acetyl CoA) required step between glycolysis and the Krebs cycle

16 2 Pyruvic Acid 2 Acetyl CoA During the conversion of each of the 2 molecules of pyruvic acid to Acetyl CoA the following occurs: Decarboxylation (CO 2 is removed) of pyruvic acid making acetic acid (2 carbons) One H is removed from acetic acid (oxidized) by NAD + (reduced to NADH) and further contributes to the H + gradient Coenzyme A in the mitochondrial matrix is added to the acetic acid to make acetyl CoA During this step the products are: 2 molecules of CO 2 2 molecules of NADH 2 molecules of Acetyl CoA used in the Krebs Cycle

17 Krebs Cycle (Citric Acid Cycle) A series of 10 biochemical reactions which begins and ends (cyclic) with a molecule of citric acid Each acetic acid (2 carbons) is combined with a molecule of oxaloacetic acid in the mitochondrial matrix (4 carbons) to make citric acid (6 carbons) during step 1 Each citric acid is then decarboxylated twice (steps 4 and 6) and oxidized (H is removed during steps 3, 5, 8 and 10) as it is converted into different carbohydrate intermediates energy released from the hydrolysis of bonds is used to synthesize ATP during step 7 NAD + (steps 3, 5 and 10) and FAD (step 8) are reduced to NADH and FADH 2 and further contributes to the H + gradient in the mitochondria

18 Krebs Cycle

19 Products of Krebs Cycle The reactions of the Krebs cycle produce: 3 molecules of NADH 1 molecule of FADH 2 2 molecules of CO 2 1 molecule of ATP 1 molecule of oxaloacetic acid Since each molecule of glucose yields two molecules of acetyl CoA, 2 Krebs cycles yield: 6 NADH 2 FADH 2 4 CO 2 2 ATP 2 oxaloacetic acid reenter the Krebs cycle of reactions after combined with another acetic acid

20 Products of Glycolysis Krebs Cycle 4 ATP 2(net) from glycolysis 2 from Krebs 10 NADH (10 H from original glucose molecule) 2from glycolysis 2 from (2) Pyruvic Acid (2)Acetyl CoA 6 from Krebs 2 FADH 2 (2 H from original glucose molecule) 2 from Krebs 6 CO 2 (6 C from original glucose molecule) 2 from (2) Pyruvic Acid (2)Acetyl CoA 4 from Krebs

21 CO 2 ATP ADP NAD ADP NADH ADP ATP ATP 3C Pyruvic Acid NAD CO 2 NADH CoA 2C Acetyl CoA 2C Acetate + OAA 4C NAD 6C Citric Acid NADH CO 2 NAD NADH FADH NADH ATP 2 FAD NAD ADP 4C OAA 6C Glucose CO 2 ATP ADP NAD ADP NADH ATP ADP 3C Pyruvic Acid ATP NADH NAD CO 2 CoA 2C Acetyl CoA 2C Acetate + OAA 4C 6C Citric Acid NADH CO 2 NAD NADH FADH NADH ATP 2 FAD NAD ADP 4C OAA GLYCOLYSIS KREBS (CITRIC ACID) CYCLE CYTOPLASM MITOCHONDIAL MATRIX

22 Electron Transport Chain A group of 3 integral proteins and 2 membrane coenzymes associated with the inner mitochondrial membrane called the electron transport chain (ETC) creates a H + gradient between the intermembrane space and the matrix of the mitochondria using the H of from NADH and FADH 2 that accumulate in the mitochondrial matrix as products of glycolysis and the Krebs cycle 3 (integral) enzyme complexes of the ETC remove the H from NADH and FADH 2 (oxidized back to NAD + and FAD + ) in the matrix

23 ETC and Oxidative Phosphorylation FADH 2 FAD +

24 NADH and the Electron Transport Chain NADH is oxidized by Enzyme complex 1 of the ETC The H that is removed by Enzyme complex 1 is split into an electron (e - ) and a proton (H + ) The e - is passed from the beginning to the end of the ETC and energizes the 1 st, 2 nd and 3 rd Enzyme complexes along the way Once energized, each enzyme complex pumps a free proton from the mitochondrial matrix into the intermembrane space (3 total)

25 FADH 2 and the Electron Transport Chain FADH 2 is oxidized by Enzyme complex 2 of the ETC The H that is removed by Enzyme complex 2 is split into an electron (e - ) and a proton (H + ) The e - is passed to the end of the ETC and energizes the 2 nd and 3 rd Enzyme complexes along the way Once energized, each enzyme complex pumps a free proton from the mitochondrial matrix into the intermembrane space (2 total)

26 Proton (H + ) gradient The movement of protons from the matrix into the intermembrane space creates a high H + (ph = 7) concentration in the intermembrane space and a low H + (ph = 8) concentration in the matrix this proton gradient becomes the source of energy used by the mitochondria to synthesize ATP, which is released as H + diffuse from the intermembrane space back into the matrix The oxidation of NADH contributes more (pumps 3 H + ) to the proton gradient than FADH 2 (pumps 2 H + )

27 ATP Synthase ATP synthase is an integral membrane protein in the inner mitochondrial membrane that has 2 functions: it acts as a H + channel allows H + to diffuse down its gradient from the intermembrane space into the matrix it acts as an enzyme uses the energy that is released by the diffusion of H + to synthesize ATP from ADP and P This type of ATP synthesis is called oxidative phosphorylation because, this process requires the oxidation of NADH and FADH 2

28 ATP Synthesis During Oxidative Phosphorylation Because the oxidation of NADH contributes more to the proton gradient than the oxidation of FADH 2, more ATP is synthesized from NADH than FADH 2 On average, for each NADH that is oxidized 3 molecules of ATP are synthesized 10 NADH x 3 ATP = 30 ATP On average, for each FADH 2 that is oxidized 2 molecules of ATP are synthesized 2 FADH 2 x 2 ATP = 4 ATP 34 of the 38 molecules of ATP are synthesized by oxidative phosphorylation

29 Formation of Water After the electrons arrive to the last enzyme complex of the ETC they are transferred to atoms of oxygen in the mitochondrial matrix this makes oxygen especially negative In the matrix, these oxygen atom are combined with the H + that have diffused back into the matrix from the intermembrane space to form water (H 2 O) the protons become reunited with their electron

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