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Semester 2: Cellular Metabolism
Glycolysis, gluconeogenesis, pentose phosphate pathway, glycogen metabolism
Cellular Metabolism
Glycolysis
Glycolysis is the metabolic pathway that converts glucose into pyruvate, yielding ATP and NADH as energy carriers. This process occurs in the cytoplasm and consists of ten enzyme-catalyzed steps, divided into two phases: the energy investment phase and the energy payoff phase. Glycolysis is anaerobic and can occur without oxygen.
Gluconeogenesis
Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors, primarily occurring in the liver and to a lesser extent in the kidney. This metabolic pathway is essentially the reverse of glycolysis, utilizing different enzymes to bypass the irreversible steps of glycolysis. It plays a crucial role in maintaining blood glucose levels during fasting or intense exercise.
Pentose Phosphate Pathway
The pentose phosphate pathway is a metabolic pathway parallel to glycolysis that generates NADPH and ribose-5-phosphate. NADPH is essential for anabolic reactions and maintaining redox balance, while ribose-5-phosphate is a precursor for nucleotide synthesis. This pathway is divided into an oxidative phase, which generates NADPH, and a non-oxidative phase, which interconverts sugars.
Glycogen Metabolism
Glycogen metabolism involves the synthesis (glycogenesis) and breakdown (glycogenolysis) of glycogen, the stored form of glucose in animals. Glycogenesis occurs in response to insulin and allows for the storage of glucose in liver and muscle cells. Glycogenolysis, regulated by glucagon and epinephrine, mobilizes glucose during fasting or exercise. Enzymes such as glycogen phosphorylase and glycogen synthase play key roles in these processes.
Fatty acid oxidation and biosynthesis, ketogenesis, eicosanoids biosynthesis
Fatty Acid Oxidation and Biosynthesis, Ketogenesis, Eicosanoids Biosynthesis
Fatty Acid Oxidation
Fatty acid oxidation occurs primarily in the mitochondria and is the process by which fatty acids are broken down to produce acetyl-CoA, which can enter the citric acid cycle for energy production. The main mechanism involves the activation of fatty acids to form acyl-CoA, which then undergoes a series of beta-oxidation cycles, resulting in the release of acetyl-CoA, NADH, and FADH2.
Fatty Acid Biosynthesis
Fatty acid biosynthesis takes place in the cytoplasm and is essentially the reverse of fatty acid oxidation. The process is initiated by the enzyme acetyl-CoA carboxylase, which converts acetyl-CoA to malonyl-CoA. The fatty acid synthase complex then assembles fatty acids through a series of condensation reactions, reduction, dehydration, and another reduction, eventually producing long-chain fatty acids.
Ketogenesis
Ketogenesis is the metabolic pathway that converts fatty acids into ketone bodies, primarily occurring in the liver during periods of fasting or prolonged exercise. The process starts with the conversion of acetyl-CoA into acetoacetate, which can then be reduced to beta-hydroxybutyrate or decarboxylated to produce acetone. Ketone bodies serve as an alternative energy source, especially for the brain during low carbohydrate availability.
Eicosanoids Biosynthesis
Eicosanoids are signaling molecules derived from fatty acids, particularly arachidonic acid. The biosynthesis of eicosanoids involves the action of cyclooxygenases (COX) and lipoxygenases (LOX), leading to the formation of prostaglandins, thromboxanes, and leukotrienes. These compounds play critical roles in inflammation, immunity, and other physiological processes.
Nucleotide metabolism: synthesis, salvage, degradation
Nucleotide metabolism: synthesis, salvage, degradation
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Nucleotide synthesis involves the creation of nucleotides, the building blocks of nucleic acids.
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The process of synthesizing nucleotides from simpler molecules such as amino acids and carbon skeletons.
Involves two main pathways: purine and pyrimidine synthesis. Purine synthesis begins with ribose-5-phosphate and incorporates amino acids like glycine and aspartate. Pyrimidine synthesis starts with carbon dioxide and ammonia.
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Recycling of nucleotides from degraded nucleic acids.
Utilizes enzymes to convert nucleobases released during nucleic acid breakdown back into nucleotides. This pathway helps to conserve energy.
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Nucleotide salvage refers to the reassembly of nucleotides from free bases and nucleosides.
Allows cells to conserve energy by reusing nucleotide components instead of synthesizing them from scratch.
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Phosphorylate nucleosides to form nucleotides.
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Catalyzes the conversion of hypoxanthine and guanine to their respective nucleotides, IMP and GMP.
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The breakdown of nucleotides into their constituent parts.
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Involves the hydrolysis of nucleotides to nucleosides, followed by the breakdown of nucleosides to nucleobases and further to ammonia and urea.
Recycles components and allows for the disposal of excess nucleotides.
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Specifically breaks down purines into uric acid as a waste product.
Dysregulation can lead to disorders such as gout.
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Yields products such as beta-alanine and ammonia, which are less harmful than purine degradation products.
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Aberrations in nucleotide metabolism can lead to various diseases, including genetic disorders and cancers.
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Leads to the accumulation of toxic metabolites, resulting in immunodeficiency.
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Caused by a deficiency in HGPRT, leading to significant neurodevelopmental issues and gout.
Amino acid biosynthesis and degradation
Amino acid biosynthesis and degradation
Introduction to Amino Acids
Amino acids are organic compounds that serve as the building blocks of proteins. They play critical roles in various physiological processes and are classified as essential and non-essential amino acids.
Biosynthesis of Amino Acids
Amino acids are synthesized in cells through various pathways. The biosynthesis involves key intermediates of central metabolic pathways and is categorized into two main groups: biosynthesis from primary metabolites and biosynthesis using other amino acids.
Pathways of Amino Acid Biosynthesis
Different amino acids are synthesized through specific pathways. For example, serine is derived from 3-phosphoglycerate, and tryptophan is synthesized from chorismate. These pathways involve various enzymes and cofactors.
Regulation of Amino Acid Biosynthesis
Biosynthetic pathways are tightly regulated through feedback inhibition and allosteric regulation to maintain cellular homeostasis and respond to metabolic needs.
Degradation of Amino Acids
Amino acid degradation involves the removal of the amino group and the subsequent conversion of the carbon skeleton into various intermediates that enter the Krebs cycle or other metabolic pathways.
Importance of Amino Acid Catabolism
The degradation of amino acids provides energy, and carbon skeletons for gluconeogenesis and ketogenic metabolism, along with the detoxification of excess nitrogen through the urea cycle.
Clinical Significance
Disruptions in amino acid biosynthesis or degradation can lead to metabolic disorders, indicating the importance of these processes in health and disease.
Heme biosynthesis and sulfur metabolism
Heme biosynthesis and sulfur metabolism
Introduction to Heme Biosynthesis
Heme is an iron-containing prosthetic group found in hemoglobin, myoglobin, and various cytochromes. Its biosynthesis occurs primarily in the liver and bone marrow, involving eight enzymatic steps. The first step starts in the mitochondria with the condensation of succinyl-CoA and glycine to form 5-aminolevulinic acid (ALA). Subsequent steps involve the formation of porphobilinogen, hydroxymethylbilane, uroporphyrinogen, coproporphyrinogen, protoporphyrin, and finally heme.
Key Enzymes in Heme Biosynthesis
The key enzymes involved include ALA synthase, ALA dehydratase, uroporphyrinogen III synthase, and ferrochelatase. ALA synthase is the rate-limiting enzyme, and its activity is regulated by heme levels and various metabolic signals. Disorders in heme synthesis can lead to porphyrias, characterized by an accumulation of porphyrins.
Regulation of Heme Biosynthesis
Heme biosynthesis is tightly regulated at multiple levels, including transcriptional regulation of ALA synthase and feedback inhibition by heme itself. Additionally, cellular oxygen levels influence heme synthesis, linking it to cellular respiration.
Introduction to Sulfur Metabolism
Sulfur metabolism involves the conversion of sulfur-containing compounds in the body. Sulfur is an essential element for synthesizing amino acids cysteine and methionine. It plays a significant role in various biochemical processes, including detoxification and the formation of coenzymes.
Key Pathways in Sulfur Metabolism
The primary pathways include the assimilation of sulfate into cysteine through the sulfate activation pathway and the transsulfuration pathway, which converts homocysteine to cysteine. These pathways are crucial for maintaining sulfur homeostasis and ensuring an adequate supply of sulfur for cellular processes.
Regulation of Sulfur Metabolism
Sulfur metabolism is regulated through feedback mechanisms involving amino acid levels and cellular demand for sulfur. The availability of sulfate in the environment and the substrate concentration also influence the metabolic flux through these pathways.
Interconnection between Heme Biosynthesis and Sulfur Metabolism
Both heme biosynthesis and sulfur metabolism are interconnected as cysteine is involved in the synthesis of heme. Cysteine can serve as a precursor to various biologically active molecules, influencing the availability of iron and the overall redox status in cells.
