Biochemistry lecture notes metabolism_tca cycle; glyoxalate cycle
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The citric acid cycle is a central metabolic pathway that occurs in the mitochondrion of aerobic organisms. It involves 8 reactions that completely oxidize a two-carbon acetyl group to carbon dioxide, producing reduced coenzymes like NADH and FADH2 that are used in ATP synthesis. The cycle is regulated by enzymes that respond to levels of ATP, NADH, and other products to adjust the rate of the cycle to meet cellular energy needs. A related glyoxylate cycle allows plants and bacteria to convert fatty acids into glucose for biosynthesis.
Biochemistry lecture notes metabolism_tca cycle; glyoxalate cycle
- 1. REGULATION OF METABOLIC PATHWAYS Dr.B.RENGESH | M.Tech., Ph.D. Associate Professor, Department of Pharmaceutical Technology, Mahendra Engineering College (Autonomous), Namakkal District, Tamil Nadu, India
- 2. THE CITRIC ACID CYCLE • The Kreb’s Cycle or Citric acid Cycle is the central metabolic pathway in all aerobic organisms. The cycle is a series of eight reactions that occur in the mitochondrion. These reactions take a two carbon molecule (acetate) and completely oxidize it to carbon dioxide. – The citric acid cycle is also known as the tricarboxylic acid cycle (TCA cycle) because of the three carboxylic acid groups in citric acid, and the Krebs cycle after Hans A. Krebs, who deduced the reaction sequence in 1937.
- 3. TCA cycle Animation Video: https://www.sigmaaldrich.com/technical- documents/articles/biofiles/citric-acid-cycle.html ⓵ ⓶ ⓶ ⓷ ⓸⓹ ⓺ ⓻ ⓼ • The reactions of the citric acid cycle can be added to give the net equation:
- 4. TCA cycle • The citric acid cycle is the principal process for generating the reduced coenzymes NADH and FADH2, which are necessary for the reduction of oxygen and ATP synthesis in the electron transport chain. – The citric acid cycle also functions as a source of intermediates for biosynthesis of other important molecules (e.g., some amino acids). • The reactions of the citric acid cycle occur within the matrix of the mitochondria. • There are eight reactions in the cycle. Of particular importance are the reactions where NADH (Steps 3, 4, and 8) and FADH2 (Step 6) are produced. • A two-carbon acetyl group enters the cycle (Step 1) and two carbon atoms are liberated as CO2 molecules (Steps 3 and 4) • This series of reactions begins and ends with a C4 compound, oxaloacetate (hence the term cycle).
- 5. TCA cycle Some important features of the citric acid cycle: 1. Acetyl CoA is the fuel of the citric acid cycle. 2. The operation of the cycle requires a supply of the oxidizing agents NAD+ and FAD from the electron transport chain. – Because oxygen is the final acceptor of electrons in the electron transport chain, the continued operation of the cycle depends ultimately on an adequate supply of oxygen. 3. Two carbon atoms enter the cycle as an acetyl unit, and two carbon atoms leave the cycle as two molecules of CO2. However, the carbon atoms leaving the cycle correspond to carbon atoms that entered in the previous cycle; there is a one-cycle delay between the entry of two carbon atoms as an acetyl unit and their release as CO2. 4. In each complete cycle, four oxidation-reduction reactions produce three molecules of NADH (Steps 3, 4, and 8) and one molecule of FADH2 (Step 6). 5. One molecule of the high-energy phosphate compound guanosine triphosphate (GTP) is generated (Step 5).
- 6. TCA cycle – Regulation of the Citric Acid Cycle • The rate at which the citric acid cycle operates is precisely adjusted to meet cellular needs for ATP. – Citrate synthetase (Step 1) is an allosteric enzyme that is inhibited by ATP and NADH and activated by ADP. – Isocitrate dehydrogenase (Step 3) is an allosteric enzyme that is inhibited by NADH and activated by ADP. – The a-ketoglutarate dehydrogenase complex (Step 4) is a group of allosteric enzymes that is inhibited by succinyl CoA, NADH, the products of the reaction that it catalyzes, and ATP. • The rate at which the citric acid cycle operates is reduced when cellular ATP levels are high, and stimulated when ATP supplies are low (and ADP levels are high).
- 7. GLYOXALATE CYCLE • A pathway related to the Citric Acid Cycle (CAC) is the glyoxylate pathway (Figure). This pathway, which overlaps all of the non-decarboxylation reactions of the CAC does not operate in animals, because they lack two enzymes necessary for the pathway – isocitrate lyase and malate synthase. Isocitrate lyase catalyzes the conversion of isocitrate into succinate and glyoxylate. Because of this, all six carbons of the CAC survive and do not end up as carbon dioxide.
- 8. Glyoxalate Cycle • Succinate continues through the remaining reactions of the CAC to produce oxaloacetate. Glyoxylate combines with another acetyl-CoA (one acetyl-CoA was used to start the cycle) to create malate (catalyzed by malate synthase). Malate can, in turn, be oxidized to oxaloacetate. • It is at this point that the pathway’s contrast with the CAC is apparent. After one turn of the CAC, a single oxaloacetate is produced and it balances the single one used in the first reaction of the cycle. Thus, in the CAC, no net production of oxaloacetate is realized. By contrast, at the end of a turn of the glyoxylate cycle, two oxaloacetates are produced, starting with one. The extra oxaloacetate can then be used to make other molecules, including glucose in gluconeogenesis. • Because animals do not run the glyoxylate cycle, they cannot produce glucose from acetyl- CoA in net amounts, but plants and bacteria can. As a result, these organisms can turn acetyl-CoA from fat into glucose, while animals can’t. Bypassing the decarboxylations (and substrate level phosphorylation) has its costs, however. Each turn of the glyoxylate cycle produces one FADH and one NADH instead of the three NADHs, one FADH2 and one GTP made in each turn of the CAC.