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biochem recitation 2.22
Chapter 16: The Citric Acid Cycle
Overview of the Citric Acid Cycle
The citric acid cycle (CAC), also known as the Krebs cycle, plays a critical role in cellular respiration.
Understanding the CAC enhances comprehension of the metabolism of fats and amino acids, as they are interconnected.
Energy Production in the Citric Acid Cycle
Oxidative Decarboxylation: Pyruvate is converted to Acetyl-CoA using the
Enzyme: Pyruvate dehydrogenase complex
Cofactors: FAD, NAD, TPP, Lipoic acid
Products: NADH, Acetyl-CoA, CO2
Energy-producing steps in the CAC:
Isocitrate to Alpha-Ketoglutarate - Produces NADH
Alpha-Ketoglutarate to Succinyl-CoA - Produces NADH
Succinyl-CoA to Succinate - Produces ATP
Succinate to Fumarate - Produces FADH2
Malate to Oxaloacetate - Produces NADH
Summary of products from one turn of the cycle:
3 NADH, 1 FADH2, 1 ATP for each Acetyl-CoA.
Malate-Aspartate Shuttle
Each NADH produced requires NAD+ for regeneration, which is facilitated by the malate-aspartate shuttle.
It plays a crucial role in linking pathways like gluconeogenesis and the CAC.
Concepts of Glycolysis and Citric Acid Cycle
Glycolysis converts glucose to two pyruvates:
This step occurs in the cytosol and produces 2 ATP, 2 NADH.
Each pyruvate is then converted to Acetyl-CoA for entry into the CAC.
Energy and Products from Different Inputs
For one glucose molecule:
Produces 2 pyruvates -> 2 Acetyl-CoA -> Results in 6 NADH, 2 FADH2, 4 CO2, 2 ATP in CAC.
Amphibolic Nature of the Citric Acid Cycle
The CAC is both catabolic (energy-producing) and anabolic (precursor for biosynthesis).
Intermediates are involved in synthesizing glucose, amino acids, and fatty acids.
Regulation of the Citric Acid Cycle
High-energy molecules (NADH, ATP, citrate, succinyl-CoA) inhibit the CAC.
Low-energy molecules (ADP, calcium ions, NAD+) stimulate the cycle.
Key regulatory enzymes:
Pyruvate dehydrogenase complex (PDH)
Alpha-ketoglutarate dehydrogenase complex
Fatty Acid Oxidation Overview
Fatty acids undergo four reactions during beta-oxidation:
Oxidation to form a double bond (produces FADH2)
Hydration reaction
Oxidation again (produces NADH)
Cleaving off Acetyl-CoA
Each cycle of fatty acid oxidation yields energy carriers (NADH, FADH2) and reduces carbon atoms by two.
Distinctions in Unsaturated Fatty Acid Processing
Unsaturated fatty acids skip the first oxidation step, decreasing the yield of FADH2.
For each additional double bond beyond the first, one NADH is lost due to necessary reduction reactions.
Amino Acid Catabolism
Amino acids can be broken down for energy through transamination and deamination.
Two main pathways occur:
Glutamate is formed through transamination, which can then be deaminated to release nitrogen into the urea cycle.
Excess amino groups are converted into non-toxic compounds (e.g., glutamine in the brain), which are sent to the liver.
Urea Cycle Connection
The urea cycle incorporates nitrogen from amino acid breakdown into urea for excretion.
Key regulatory mechanisms respond to changes in amino acid levels, with high levels stimulating urea cycle activity.
Key Takeaways for Exam Preparation
Understand the stepwise processes of CAC and fatty acid oxidation, emphasizing connections to glycolysis and amino acid metabolism.
Focus on memorizing key products and regulatory points but aim to understand broader metabolic contexts rather than rote memorization.
Chapter 16: The Citric Acid Cycle
Overview of the Citric Acid Cycle
The citric acid cycle (CAC), also known as the Krebs cycle or the tricarboxylic acid (TCA) cycle, is a crucial metabolic pathway that plays a central role in cellular respiration by metabolizing carbohydrates, fats, and proteins. This cycle occurs in the mitochondrial matrix and is essential for producing energy in the form of ATP, as well as providing key precursors for various biosynthetic processes. Understanding the CAC enhances comprehension of the interconnected nature of metabolism, particularly how fats and amino acids contribute to energy production.
Energy Production in the Citric Acid Cycle
Oxidative Decarboxylation: The entry point into the CAC begins with the conversion of pyruvate, derived from glycolysis, to Acetyl-CoA. This reaction is catalyzed by the enzyme pyruvate dehydrogenase complex, which requires several cofactors:
FAD (flavin adenine dinucleotide)
NAD+ (nicotinamide adenine dinucleotide)
TPP (thiamine pyrophosphate)
Lipoic acidThe products of this reaction are NADH, Acetyl-CoA, and CO2.
Energy-Producing Steps in the CAC: The cycle consists of several key transformations that produce energy carriers:
Isocitrate to Alpha-Ketoglutarate: Produces NADH
Alpha-Ketoglutarate to Succinyl-CoA: Produces NADH
Succinyl-CoA to Succinate: Produces ATP through substrate-level phosphorylation
Succinate to Fumarate: Produces FADH2
Malate to Oxaloacetate: Produces NADH
Summary of Products
From one complete turn of the cycle for each Acetyl-CoA, the CAC produces a total of:
3 NADH
1 FADH2
1 ATPThese energy carriers are pivotal for oxidative phosphorylation, where they ultimately lead to the production of a substantial amount of ATP in the electron transport chain.
Malate-Aspartate Shuttle
Each NADH produced in the CAC must be accompanied by a corresponding NAD+ for the regeneration of the coenzyme. The malate-aspartate shuttle facilitates this regeneration, operating predominantly in liver and heart tissues. This shuttle not only plays an essential role in the efficient transfer of electrons produced during glycolysis to the mitochondrial matrix but also contributes to the linkage of gluconeogenesis and the citric acid cycle, thereby influencing overall metabolic flux.
Concepts of Glycolysis and Citric Acid Cycle
Glycolysis converts glucose to two pyruvate molecules in the cytosol, generating 2 ATP and 2 NADH in the process. Each pyruvate is subsequently converted to Acetyl-CoA; thus:
For every glucose molecule, glycolysis yields 2 pyruvates, leading to 2 Acetyl-CoA molecules, producing a total of:
6 NADH
2 FADH2
4 CO2
2 ATP in the CAC following the complete oxidation of glucose.
Amphibolic Nature of the Citric Acid Cycle
The CAC is uniquely amphibolic, signifying that it serves both catabolic (energy-producing) and anabolic (synthesis of important biomolecules) functions. Intermediates generated during the cycle contribute to the synthesis of glucose (gluconeogenesis), amino acids (protein synthesis), and fatty acids, underscoring the versatility of the CAC in cellular metabolism.
Regulation of the Citric Acid Cycle
The CAC is tightly regulated based on the energy state of the cell. High-energy metabolites such as NADH, ATP, citrate, and succinyl-CoA act as inhibitors, slowing down the cycle's activity, whereas low-energy signals like ADP, calcium ions, and NAD+ stimulate the cycle. The key regulatory enzymes include:
Pyruvate dehydrogenase complex (PDH)
Alpha-ketoglutarate dehydrogenase complex
Fatty Acid Oxidation Overview
Fatty acids undergo a systematic series of reactions during beta-oxidation which mainly occurs in the mitochondria:
First Oxidation Step: A double bond is formed resulting in the production of FADH2.
Hydration Reaction: The double bond is hydrated to form a hydroxyl group.
Second Oxidation Step: Another oxidation step occurs, producing NADH.
Cleavage of Acetyl-CoA: This last step releases Acetyl-CoA for entry into the CAC.Each cycle of fatty acid oxidation yields energy carriers (NADH, FADH2) and reduces the carbon chain length by two.
Distinctions in Unsaturated Fatty Acid Processing
Unsaturated fatty acids present intricacies in their metabolism, as they skip one oxidation step, resulting in a decreased yield of FADH2. Furthermore, for each additional double bond in the fatty acid chain beyond the first, one NADH is lost due to necessary reduction reactions that take place during the metabolism of these compounds.
Amino Acid Catabolism
Amino acids can be catabolized for energy through two main processes: transamination and deamination.
Transamination: Forms glutamate, which can then undergo deamination to release nitrogen, integrating into the urea cycle for detoxification.
Non-toxic Compounds: Excess amino groups are often converted into safer derivatives (e.g., glutamine in the brain) that are then transported to the liver for further processing.
Urea Cycle Connection
The urea cycle is responsible for incorporating nitrogen from amino acid breakdown into urea, which is excreted from the body. The activity of this cycle is subject to regulation and responds dynamically to changes in amino acid levels; elevated amino acids can stimulate urea cycle activity, thus ensuring the efficient removal of excess nitrogen.
Key Takeaways for Exam Preparation
When studying the CAC and its related processes, it is essential to understand the stepwise mechanisms involved in both the CAC and fatty acid oxidation. Emphasis should be placed on recognizing connections to glucose metabolism and amino acid utilization, while also focusing on memorizing key products and regulatory mechanisms to grasp broader metabolic contexts rather than relying solely on rote memorization.
