CHAPTER 23: Unit 3. ATP Energy from Glucose
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| Specifically, during cellular respiration, the energy stored in glucose is transferred to ATP. ATP, or adenosine triphosphate, is chemical energy the cell can use. During cellular respiration, glucose, in the presence of oxygen, is converted into carbon dioxide and water. |
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| The total ATP for the complete oxidation of glucose under aerobic conditions is calculated by combining the ATP produced from glucose, the oxidation of pyruvate, the citric acid cycle and electron transport. |
| i) ATP from Glycolysis |
| The energy‐yielding steps of glycolysis involve reactions of 3‐carbon compounds to yield ATP and reducing equivalents as NADH. The first substrate for energy production is glyceraldehyde‐3‐phosphate, which reacts with ADP, inorganic phosphate, and NAD in a reaction catalyzed by the enzyme glyceraldehyde‐3‐phosphate dehydrogenase: |
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| The reaction has several steps. In the first, a thiol carbon of the enzyme attacks the aldehyde carbon of glyceraldehyde‐3‐phosphate to make a thiohemiacetal intermediate. (Recall from organic chemistry that carbonyl carbons are electron‐poor and therefore can bond with nucleophiles, including thiols from which the proton is removed.) Next, NAD accepts two electrons from the enzyme‐bound glyceraldehyde‐3‐phosphate. The aldehyde of the substrate is oxidized to the level of a carboxylic acid in this step. Inorganic phosphate then displaces the thiol group at the oxidized carbon (carbon 1 of glyceraldehyde‐3‐phosphate) to form 1,3‐bisphosphoglycerate:The next step is the transfer of phosphate from 1,3‐bisphosphoglycerate to ADP, making ATP, catalyzed by phosphoglycerate kinase.This phase of glycolysis brings the energy balance from glucose back to zero. Two ATP phosphates were invested in making fructose‐1,6‐bisphosphate and two are now returned, one from each of the 3‐carbon units resulting from the aldolase reaction.The next reaction is the isomerization of 3‐phosphoglycerate to 2‐phosphoglycerate, catalyzed by phosphoglycerate mutase: |
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| The reaction is pulled to the right by further metabolism of 2‐phosphoglycerate. First, the compound is dehydrated by the removal of the hydroxyl group on carbon 3 and a proton from carbon 2, leaving a double bond between carbons 2 and 3. The enzyme responsible for this step is a lyase, enolase:
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ii) Malate-Aspartate Shuttle |
| The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes.The malate-aspartate shuttle (sometimes also the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction equivalents to generate ATP. The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain. To circumvent this, malate carries the reducing equivalents across the membrane.”Our heart and liver cells use a process called the malate-aspartate shuttle to transport NADH molecules produced in glycolysis into the matrix of the mitochondria. We can break down this shuttle into seven steps: (1) The NADH produced in glycolysis is used to reduce oxaloacetate into malate (2) The malate then moves into the intermembrane space and then enters the matrix via an antiporter transport system in exchange for an alpha-ketoglutarate (3) In the matrix, the malate is then oxidized back into oxaloacetate and the pair of electrons are collected by NAD+ to form an NADH molecule. This NADH can now be used by complex I of the electron transport chain (4) The oxaloacetate cannot move across the inner mitochondrial membrane and so a transamination reaction is needed to convert it into aspartate (5) The aspartate can now flow out of the inner membrane via an antiporter system in exchange for glutamate (6) The glutamate that moves into the matrix transfers an amino group onto oxaloacetate to form aspartate and alpha-ketoglutarate (7) The aspartate transported into the cytoplasm is deaminated to form oxaloacetate. The amino group is used to form glutamate.
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| Reference: https://aklectures.com/lecture/oxidative-phosphorylation/malate-aspartate-shuttle |
| iii) ATP from the Oxidation of Two Pyruvate |
| The carbon dioxide accounts for two (conversion of two pyruvate molecules) of the six carbons of the original glucose molecule. The electrons are picked up by NAD+, and the NADH carries the electrons to a later pathway for ATP production. |
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| Figure Above: Upon entering the mitochondrial matrix, a multi-enzyme complex converts pyruvate into acetyl CoA. In the process, carbon dioxide is released and one molecule of NADH is formed.Reference: https://courses.lumenlearning.com/wm-biology1/chapter/reading-pyruvate-oxidation/ |
| iv) ATP from the Citric Acid Cycle |
| The citric acid cycle uses one molecule of acetyl CoA to generate 1 ATP, 3 NADH, 1 FADH2, 2 CO2, and 3 H+. The NADH and FADH2 molecules produced in the citric acid cycle are passed along to the final phase of cellular respiration called the electron transport chain.The two acetyl CoA initially from one glucose produce 15 ATP and two FADH2, and two ATP. In electron transport, six NADH produce 15 ATP and two FADH2 produce 3 ATP. In two turn s of the citric acid cycle, a total of 20 ATP are produced. The overall equation for the reaction of two CoA is:2 Acetyl CoA ———-> 4CO2 + 20 ATP (two turns of the citric acid cycle) |
| v) ATP from the Complete Oxidation of Glucose |
| A total of 36 ATPs are gained by complete oxidation of glucose.During glycolysis, a total 4 ATPs are formed out of which 2 are consumed.Conversion of pyruvate to Acetyl CoA does produce any ATP. However, the 2 molecules of NADH+H+ are produced per glucose, which will yield 06 ATP in the ETC. The Krebs cycle produces two molecules of ATP for every molecule of glucose. The Krebs cycle also produces eight molecules of NADH and two molecules of FADH2 per molecule of glucose. As each molecule of NADH is equivalent to three ATPs and each FADH2 is equal to two ATPs, we get 2+ 8×3 + 2×2 = 30 ATPs from Krebs cycle.2 ATP is required to transport NADH + H+ formed by glycolysis from the cytoplasm through the inner mitochondrial membrane. Since 2 ATP are used, therefore only 36 ATP are produced instead of 38 ATP. |
Reference:
https://www.youtube.com/watch?v=_zR5BaeJd3k
| IV) Co-enzymes in Metabolism |
| A coenzyme is a small, organic, non-protein molecule that carries chemical groups between enzymes. In metabolism, coenzymes play a role in group-transfer reactions, such as ATP and coenzyme A, and oxidation-reduction reactions, such as NAD+ and coenzyme Q10. |
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| Figure Above: NADH (nicotinamide adenine dinucleotide is a coenzyme derived from vitamin B3).So non-protein organic cofactors are called coenzymes. Coenzymes assist enzymes in turning substrates into products. They can be used by multiple types of enzymes and change forms. Specifically, coenzymes function by activating enzymes, or acting as carriers of electrons or molecular groups. Example, al of the water-soluble vitamins and two of the fat-soluble vitamins, A and K, function as cofactors or coenzymes. Coenzymes participate in numerous biochemical reactions involving energy release or catabolism, as well as the accompanying anabolic reactions. In addition, vitamin cofactors are critical for processes involved in proper vision, blood coagulation, hormone production, and the integrity of collagen, a protein found in bones.Coenzyme A (CoASH) has a clearly defined role as a cofactor for a number of oxidative and biosynthetic reactions in intermediary metabolism. Formation of acyl-CoA thioesters from organic carboxylic acids activates the acid for further biotransformation reactions and facilitates enzyme recognition. Xenobiotic carboxylic acids can also form CoA-thioesters, and the resulting acyl-CoA may contribute to the compound’s toxicity. Generation of an unusual or poorly-metabolized acyl-CoA from a xenobiotic may lead to cellular metabolic dysfunction through several types of mechanisms including: (1) inhibition of key metabolic enzymes by the acyl-CoA; (2) sequestration of the total cellular CoA pool as the unusual acyl-CoA; (3) physical-chemical effects of the acyl-CoA; and (4) sequestration and depletion of carnitine as the acyl group is transformed from the acyl-CoA to form the corresponding acylcarnitine. Many of these toxicities are similar to sequelae observed in the inherited organic acidurias in which endogenously-generated acyl-CoAs accumulate secondary to an enzymopathy. Insights into the cellular mechanisms of xenobiotic acyl-CoA accumulation have been derived from model systems developed to understand organic acidemias, such as the methylmalonyl-CoA accumulation of the methylmalonic acidurias. The relevance of acyl-CoA accretion to human pathophysiology has now been well established, and identification of the relevant mechanism of toxicity can allow implementation of strategies to minimize the metabolic injury. Additionally, recognition of the potential for acyl-CoA mediated xenobiotic injury should result in improved rational drug design and earlier recognition of such toxicity when develops. |