BIO Week 4 Glycolysis & Krebs Cycle BNU 2024 PDF

Biochemistry Lecture Glycolysis & Krebs cycle  Faculty of Dentistry, Benha National University. Glycolysis & Krebs cycle  Objectives By the end of this lecture, the students will be able to: ❑ Define glycolysis, site, key enzymes and medical importance....

Biochemistry Lecture Glycolysis & Krebs cycle  Faculty of Dentistry, Benha National University. Glycolysis & Krebs cycle  Objectives By the end of this lecture, the students will be able to: ❑ Define glycolysis, site, key enzymes and medical importance. ❑ Explain hormonal regulation of glycolysis. ❑ Clarify Oxidative decarboxylation of pyruvate. ❑ Define citric acid cycle(Krebs cycle), site and biomedical importance. ❑ Calculate energy produced from complete oxidation of one glucose molecule.  Glucose oxidation Pathways for glucose oxidation are classified into: I. Major pathways: These pathways are grouped into three linked biochemical pathways (responsible for ATP production). A. Glycolysis: It is the first pathway which occur in the cytoplasm of every cell in presence or absence of oxygen. B. Pyruvate oxidation in the mitochondria. C. Citric acid cycle in the mitochondria. lI. Minor pathways: these pathways produce important compounds with no energy production. They include: A. Hexose monophosphate shunt (HMS) for production of pentoses and NADPH+H. B. Uronic acid pathway for production of uronic acid.  I. Glycolysis Definition: Oxidation of glucose to pyruvate (under aerobic conditions) or lactate (under anaerobic conditions). It can occur in presence (aerobic) or absence of oxygen (anaerobic). For aerobic glycolysis mitochondria must be present. Intracellular location: Cytoplasm. Organ location: Glycolysis occur in the cytoplasm of all tissue cells. The most important organs that requires glycolysis as a source of energy are: 1. Mature red blood cells because they have no mitochondria (no TCA cycle). 2. Skeletal muscles during exercise due to lack of oxygen. 3. Testes and leukocytes due to presence of few mitochondria. Steps: Steps are divided into two phases: I. First phase (ATP consuming phase or preparatory phase): Glucose undergoes activation and cleavage into two molecules of glyceraldhyde-3-posphate with utilization of 2 ATP. II. Second phase (energy producing phase): Glyceraldhyde-3- phosphate is converted to two molecules of pyruvate under aerobic conditions or two molecules of lactate under anaerobic conditions.  Key enzymes of glycolysis These are the enzymes that regulate the three irreversible reactions of glycolysis: 1. Glucokinase enzyme in the liver and hexokinase enzyme in other tissues, both acts on glucose: 2. Phosphofructokinase: is the most important regulator of glycolysis and the step is the rate limiting step: 3. Pyruvate kinase: It converts phosphoenol pyruvate to pyruvate: Glycolysis in red blood cells: Glycolysis in red blood cells occurs anaerobically (aerobic glycolysis requires presence of mitochondria while RBCs lack of mitochondria). The end of glycolysis in RBCs is 2 molecules of lactate. It produces 2ATP only. Products of glycolysis:  II- Oxidative decarboxylation of pyruvate The 2 pyruvate molecules produced from glycolysis (under aerobic conditions) are oxidized by pyruvate dehydrogenase enzyme complex (PDH) to form acetyl CoA. Pyruvate is transported at first to the inside of the mitochondria by special transporter. In the mitochondria, it is irreversibly converted to acetyl CoA by pyruvate dehydrogenase complex (PDH). Oxidative decarboxylation of two pyruvate molecules produced from glycolysis→2NADH Oxidation of one NADH → 2.5 ATP So, oxidation of 2NADH produces → 5 ATP III- Citric acid cycle(Krebs cycle) Definition: It is sequences of reactions by which acetyl CoA is oxidized to CO2, water and energy. The citric acid cycle is the final common pathway for the oxidation of carbohydrate, lipid, and protein. Site: All the steps of citric acid cycle occur in mitochondria. State: Under aerobic conditions (in the presence of oxygen). Steps: Citric acid cycle begins by condensation of acetyl CoA (2 carbons) with oxaloacetate (4 carbons) to form citrate (6 carbons) which is reconverted to oxaloacetate again by the end of the cycle. Energy produced from oxidation of 2 molecules of acetyl CoA in citric acid cycle: – Oxidation of one molecule acetyl CoA in citric acid cycle produces (10 ATP). – So, two molecules of acetyl CoA which enter citric acid cycle produce (20 ATP). Biomedical importance of citric acid cycle TCA cycle is said to be amphibolic in nature i.e., has dual functions: (I) Anabolic functions: The intermediates of the citric acid cycle are used as precursors in the biosynthesis of many compounds: – Synthesis of fatty acids from citrate. – Synthesis of ketone bodies and cholesterol from acetyl CoA. – Synthesis of glucose (gluconeogenesis). – Synthesis of some non- essential amino acids: Pyruvate→ alanine Oxaloacetate→Aspartate α- ketoglutarate→Glutamate. – Synthesis of heme from succinyl CoA and glycine amino acids. Succinyl CoA +Glycine→→→ Heme. (II) Catabolic functions: Common pathway for oxidation of carbohydrates, fatty acids and proteins. It is amphibol, which means that it is both catabolic and anabolic Energy produced from complete oxidation of one glucose molecule: 1. Glycolysis: 5-7 ATP. 2. Oxidative decarboxylation of pyruvate (2 molecules of pyruvate): 5 ATP 3. Oxidation of 2 acetyl CoA in the citric acid cycle: 20 ATP So net energy produced from complete oxidation of glucose = 30 to 32 ATP