GENETIC AND ENZYMATIC REGULATION OF CELL ACTIVITIES

1. GENETIC AND ENZYMATIC REGULATION OF CELL ACTIVITIES Presented by Raigwal khan to Dr Irfan sheikh

2. GENETIC REGULATION OF CELL ACTIVITIES INTRODUCTION The genetic regulation of cell activities is a fundamental concept in biology that revolves around the intricate mechanisms by which an organism's genetic information controls the various activities and functions of its cells. This genetic regulation is crucial for maintaining the overall health, development, and functionality of an organism. At the heart of genetic regulation are the processes that govern the expression of genes. Genes are segments of DNA that contain instructions for the synthesis of specific proteins or functional RNA molecules. Proteins are the workhorses of the cell, performing a wide range of functions such as catalyzing biochemical reactions, serving as structural components, and regulating various cellular processes. The process of genetic regulation can be broken down into several key components:

3. Nuclear Envelop Plasma Membrane • Transcription: The first step in gene expression is transcription, where a segment of DNA is used as a template to synthesize a complementary RNA molecule. This RNA molecule, known as messenger RNA (mRNA), carries the genetic information from the gene to the ribosomes, where protein synthesis occurs. • Translation:Once the mRNA has been transcribed, it leaves the cell's nucleus and enters the cytoplasm, where it binds to ribosomes. During translation, the ribosomes "read" the mRNA sequence and use it as a blueprint to assemble a specific protein by linking amino acids together in the correct order. • Regulatory Elements: In addition to the coding regions of genes (exons), genes also contain non-coding regions (introns) and regulatory elements such as promoters, enhancers, and silencers. These regulatory elements play a crucial role in controlling when and to what extent a gene is transcribed. Promoters initiate transcription, while enhancers can increase the transcription rate, and silencers can reduce it. R DNA DNA Transcription Nucleus RNA RNA Splicing RNA Transport Translation of messenger RNA Ribosomes Cytosol Protein

4. Transcription Factors: These are proteins that bind to specific DNA sequences and interact with the regulatory elements. Transcription factors can either promote or inhibit the transcription of a gene by facilitating or preventing the binding of RNA polymerase (the enzyme responsible for transcription) to the gene's promoter. • Epigenetic Modifications:Epigenetic modifications, such as DNA methylation and histone modification, can also influence gene expression. These modifications can change the accessibility of DNA to transcription machinery, effectively turning genes "on" or "off" without altering the underlying DNA sequence. • Post-transcriptional and Post-translational Modifications: After translation, proteins can undergo various modifications that further regulate their function. These modifications include phosphorylation, glycosylation, and cleavage, among others. • Cell Signaling: Cells can receive signals from their environment or neighboring cells, which can trigger changes in gene expression. These signaling pathways often involve protein receptors and intracellular signaling cascades. Gene on DNA Transcription m RNA Translation Protein formation Cell Structure Cell Enzyme Cell Function

5. Glycolysis:is a fundamental metabolic pathway responsible for breaking down glucose into pyruvate and generating ATP (adenosine triphosphate) and NADH (nicotinamide adenine dinucleotide) in the process. It is tightly regulated at multiple levels, including genetic regulation, to ensure that glucose is efficiently utilized and energy production is balanced. I'll explain the genetic regulation of glycolysis step by step: Step 1: Glucose Uptake Genes involved: GLUT proteins (e.g., GLUT1, GLUT4) Regulation:Expression of GLUT proteins on the cell membrane is regulated by insulin and other factors. Insulin stimulates the translocation of GLUT4 to the cell membrane, increasing glucose uptake.

6. Step 2: Glycolytic Enzymes • Genes involved: Various genes encoding glycolytic enzymes such as hexokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase. • Regulation:The expression of these genes is regulated by transcription factors. For example: • Hexokinase:Regulated by transcription factor Myc. • PFK-1: Allosterically activated by fructose-2,6-bisphosphate, whose levels are controlled by the enzyme PFK-2, the expression of which is regulated by hormones like insulin and glucagon. • Pyruvate Kinase: Regulated by allosteric effectors and phosphorylation.

7. Step 3: Transcriptional Regulation: • Genes involved: Transcription factors like CREB, NF-κB, (Nuclear Factor-κB)HIF-1α, and SREBP-1c (Sterol Regulatory Element-Binding Protein 1c) • Regulation: These transcription factors bind to the promoters of glycolytic genes and modulate their expression. For example: • HIF-1α:Hypoxia-Inducible Factor 1-alpha) Activated in low-oxygen conditions (hypoxia) and upregulates glycolytic genes. • SREBP-1c:(cAMP Response Element-Binding Protein) Regulates the expression of lipogenic and glycolytic genes in response to insulin.

8. Step 4: Post-Transcriptional Regulation • Genes involved: MicroRNAs (miRNAs) can target glycolytic enzyme mRNAs. • Regulation: miRNAs like miR-143 and miR-155 can bind to glycolytic enzyme mRNAs, affecting their stability and translation. • Step 5: Post-Translational Regulation • Genes involved: Genes that encode kinases and phosphatases. • Regulation: Glycolytic enzymes can be regulated through phosphorylation and DE phosphorylation. For example, pyruvate kinase is activated by DE phosphorylation.

9. Step 6: Feedback Inhibition • Genes involved: Genes encoding allosteric enzymes. • Regulation: Allosteric enzymes like PFK-1 and pyruvate kinase are regulated by feedback inhibition. High levels of ATP and citrate inhibit PFK-1, while ATP and acetyl-CoA inhibit pyruvate kinase. • Step 7: Epigenetic Regulation • Genes involved: Genes involved in DNA methylation and histone modification. • Regulation: Epigenetic modifications can influence the accessibility of glycolytic gene promoters, impacting their expression.

10. Step 8: Hormonal Regulation • Genes involved: Genes that encode hormone receptors and signaling • Regulation: Hormones like insulin and glucagon activate intracellular signaling pathways that influence glycolytic gene expression. • Step 9: Cell Signaling • Genes involved: Genes that encode components of signaling pathways. • Regulation: Cell signaling pathways can modulate the activity of glycolytic enzymes through phosphorylation and other post-translational modifications.

11. The genetic regulation of glycolysis is a highly coordinated and multifaceted process involving the expression, activity, and regulation of various genes and transcription factors. It allows cells to adjust their glycolytic activity to meet their energy demands, respond to changing conditions, and maintain metabolic homeostasis. The specific genes involved may vary depending on cell type and environmental factors.

12. Temperature Regulation • Beginning: Genes involved in thermoregulation, such as UCP1 (uncoupling protein 1) in brown adipose tissue. • Trigger: Exposure to cold temperatures activates thermogenesis to maintain body warmth. • Gene Activation and Heat Production: • Cold Exposure: The body detects a drop in temperature. • Gene Activation: UCP1 gene is activated. • Thermogenesis: UCP1 protein uncouples oxidative phosphorylation, producing heat instead of ATP. • Middle: • Heat Generation: Thermogenesis raises body temperature by burning stored energy. • End - Termination: • Warmth Achieved: Once body temperature returns to normal, the need for UCP1 activation decreases. • Gene Deactivation: UCP1 gene activation diminishes. • Termination Point: • Thermal Equilibrium: The body maintains a stable core temperature, ensuring optimal physiological function.

13. Digestive Enzyme Production . Beginning: - Genes: Genes like AMY1 (amylase 1) and pepsinogen genes regulate digestive enzyme production. - Trigger: Food ingestion initiates the digestive process. Gene Activation and Enzyme Production: Food Ingestion: Ingested food signals the need for digestion. Gene Activation: Genes like AMY1 and pepsinogen genes are activated. Enzyme Synthesis: These genes produce enzymes (amylase and pepsin) necessary for digestion. Middle: Enzymatic Digestion: Amylase breaks down carbohydrates, and pepsin aids in protein digestion in the stomach. End - Termination: Digestion Complete: As food is digested, the need for enzyme production decreases. Gene Deactivation: Genes involved in enzyme production return to an inactive state. Termination Point: Effective Digestion: Food is effectively broken down, facilitating nutrient absorption.

14. Insulin Regulation of Blood Sugar • Beginning: • Genes: The INS (insulin) gene is responsible for encoding insulin, a hormone essential for blood sugar regulation. • Trigger: After a meal, when blood glucose levels rise, glucose is detected by pancreatic beta cells. • Gene Activation and Insulin Production: • Glucose Detection: High blood glucose levels trigger the activation of the INS gene. • Insulin Production: The activated INS gene leads to the synthesis of insulin. • Insulin Release: Insulin is released into the bloodstream by pancreatic beta cells. • Middle: • Target Cells: Insulin affects various tissues, especially muscle, adipose (fat), and liver cells.

15. Glucose Uptake: When insulin binds to its receptors on target cells, it facilitates the uptake of glucose from the bloodstream into these cells. • Storage and Utilization: Inside the cells, glucose can be stored as glycogen in the liver and muscles or used for energy production. • End - Termination: • Blood Sugar Lowering: As insulin promotes glucose uptake, blood sugar levels decrease. • Negative Feedback: As blood sugar levels return to normal, the need for insulin decreases. • Gene Deactivation: When blood sugar levels stabilize, the INS gene's activation decreases, leading to a reduction in insulin production. • Termination Point: • Stable Blood Sugar: The blood sugar level is maintained within a healthy range, ensuring energy supply to cells and preventing hyperglycemia (high blood sugar).

16. ENZYMATIC REGULATION OF CELL ACTIVITIES INTRODUCTION • Enzymatic regulation in physiology refers to the precise control and modulation of biochemical reactions within living organisms by enzymes. Enzymes are biological catalysts that accelerate the rate of chemical reactions, allowing them to occur at biologically relevant speeds. This regulation is fundamental to maintaining the delicate balance of physiological processes required for life. • Enzyme: An enzyme is a specialized protein that acts as a catalyst, facilitating chemical reactions by lowering the activation energy required for the reaction to occur. Enzymes are highly specific, each one designed to catalyze a particular chemical reaction or a group of related reactions.

17. Enzymatic Regulation: Enzymatic Regulation: Enzymatic regulation involves the control of enzyme activity to ensure that metabolic pathways, signaling cascades, and cellular processes proceed with precision. This regulation occurs through various mechanisms, including feedback inhibition, allosteric regulation, post-translational modifications, and gene expression control. In physiological contexts, enzymatic regulation plays a central role in numerous processes, such as energy metabolism, cellular respiration, digestion, hormone regulation, and the maintenance of homeostasis. It enables organisms to respond to changing environmental conditions, adapt to internal fluctuations, and optimize energy utilization.

18. Role of Enzymes in Cellular Processes • Enzymes play a crucial role in cellular processes by serving as biological catalysts, which means they accelerate chemical reactions within cells. Without enzymes, many of these reactions would occur too slowly to sustain life. Enzymes are essential for various cellular processes, and their functions can be illustrated through several examples: • Metabolism Regulation: • DNA Replication: • Protein Synthesis: • Digestion: • Cell Signaling: • Detoxification:

19. MECHANISMS FOR ENZYMATIC REGULATION OF CELL ACTIVITIES The mechanisms of enzymatic regulation are: • Allosteric Regulation • Covalent Modification • Feedback Inhibition • Competitive Inhibition • Non-competitive Inhibition • Enzyme Induction and Repression • pH Regulation • Temperature Regulation • Cofactors and Coenzymes • Substrate Availability

20. Allosteric Regulation: In this mechanism, molecules bind to specific regulatory sites on enzymes, known as allosteric sites, to either activate or inhibit their activity. The binding of these molecules can change the enzyme's conformation and affect its catalytic activity.

21. Co-factor Binding • Definition: Co-factor binding is the interaction between enzymes and specific molecules (co-factors) that are required for the enzyme to perform its biological function effectively. Co-factors can be either inorganic ions or organic molecules, and they assist enzymes by participating in chemical reactions or stabilizing the enzyme's structure. • Examples of Co-factors: • Mg²⁺ (Magnesium Ion): • Co-factor for enzymes involved in DNA replication, like DNA polymerase. • Fe²⁺ (Iron Ion): • Found in the heme group of hemoglobin, facilitating oxygen binding and transport. • Zn²⁺ (Zinc Ion): • Essential for the catalytic activity of many metalloenzymes, such as carbonic anhydrase. • NAD⁺ (Nicotinamide Adenine Dinucleotide): • An organic co-factor involved in redox reactions, like those catalyzed by dehydrogenases. • FAD (Flavin Adenine Dinucleotide): • A co-factor for flavoproteins, participating in a variety of oxidation-reduction reactions. • ATP (Adenosine Triphosphate): • Serves as a co-factor for enzymes involved in energy transfer, such as kinases. • Coenzyme A (CoA): • Involved in numerous metabolic pathways, carrying and transferring acyl groups.

22. Example 1: Glycolysis Regulation • Step 1: Glycolysis is the process of breaking down glucose into pyruvate. • Step 2: The enzyme Phosphofructokinase-1 (PFK-1) catalyzes an important step in glycolysis. • Step 3: Regulation: PFK-1 is inhibited by high levels of ATP, indicating that the cell has sufficient energy. • Step 4: Activation: PFK-1 is activated by low ATP levels, signaling that the cell needs more energy.

23. BLOOD VESSELS INSULINE BLOOD GLUCOSE • Example 3: Glycogen Synthesis Regulation • Step 1: Glycogen is a storage form of glucose in the liver and muscles. • Step 2: Glycogen synthase is the enzyme responsible for adding glucose units to glycogen. • Step 3: Regulation: Glycogen synthase is activated by insulin when blood glucose levels are high. GLYCOGEN SYNTHASE ACTIVATES LIVER MUSCLES

24. Example 2: Citric Acid Cycle (Krebs Cycle) Regulation • Step 1: The citric acid cycle is a series of chemical reactions that occur in the mitochondria. • Step 2: Isocitrate dehydrogenase is an enzyme involved in this cycle. • Step 3: Regulation: Isocitrate dehydrogenase is inhibited by high levels of ATP and NADH, indicating ample energy.