MPharm Programme Enzymes Lecture Week 13

Enzymes are catalysts that help speed up biochemical reactions in the body.

They are named based on their substrate or catalytic action, with the suffix "-ase" added.

Classification of enzymes is based on the type of reaction they catalyze, including oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.

Enzymes are proteins with a globular shape and a complex 3-D structure.

They have an active site, a unique shape and chemical environment that determines which substrate(s) will bind.

Some enzymes require cofactors, non-protein chemical components that act as helpers, to function properly.

Cofactors can be metal ions or organic/metallo-organic molecules called cofactors, which are either tightly or loosely bound to the enzyme.

Enzymes are essential for life as they catalyze cellular metabolic reactions, which include anabolism (biosynthesis) and catabolism (degradation).

Anabolism involves the formation of bonds between molecules, while catabolism involves the breaking of bonds between molecules.

Enzymes lower the activation energy required for metabolic reactions to proceed and enable them to occur at a faster rate.

Catabolic reactions release energy, while anabolic reactions consume energy.

Enzymes are crucial for the conversion of food into energy and the synthesis of complex molecules like proteins and carbohydrates.

Enzymes work by lowering the energy barrier to reaction, allowing substrates to reach the transition state, where existing bonds can be broken and new ones formed.

Pharmacology is the study of the interaction between drugs and the living body.

It consists of three main branches: Pharmacodynamics (study of drug effects), Pharmacokinetics (study of how the body deals with drugs), and Pharmacotherapeutics (study of drug use in disease treatment).

Drugs can interact with biological systems in two ways: non-specifically, through physical or chemical means, or specifically, by binding to specific macromolecular targets called 'receptors'.

Most drugs act specifically and bind to receptors, which are protein or glycoprotein entities, located on the cell membrane or inside the cell.

Drug receptors are responsible for initiating the chain of biochemical events leading to the drug's observed biological effects.

Drug-receptor interactions are based on the 'lock and key' relationship, where the drug's molecular structure and shape are similar to those of the natural chemical messengers, and there is a complementary fit between the drug molecule and the binding site on the receptor.

The drug-receptor interaction is reversible and governed by the Law of Mass Action.

The fraction of receptors occupied by the drug is a function of drug concentration and the equilibrium dissociation constant (KD) for the drug-receptor complex.

The 'Receptor Occupancy Theory' assumes that drug effect is proportional to the fraction of receptors occupied, and maximum drug effect occurs when all receptors in the system are occupied by the drug.

Drug concentration and drug effect can be related to the fraction of receptors occupied using various drug concentration-effect curves, such as the Emax drug concentration curve and the log drug concentration-effect curve.

Drug-Drug Interactions is a type of interaction between two drugs that affects each other's actions.

There are different types of drug-drug interactions, including drug antagonism, synergism/potentiation, and chemical, pharmacokinetic, and physiological or functional antagonism.

Drug antagonism is an interaction where one drug diminishes or abolishes the effect of another drug.

Competitive antagonism occurs when both drugs compete for the same receptor binding site, with the antagonist drug reducing the chances of agonist binding.

Reversible competitive antagonism allows both drugs to bind to the receptor, with the fraction of receptors occupied depending on their relative receptor affinities and concentrations. This type of antagonism can be overcome by increasing the concentration of the agonist drug.

Irreversible competitive antagonism involves the antagonist drug binding irreversibly to the receptor, with a fraction of receptors rendered permanently unavailable for agonist drug binding. This type of antagonism cannot be overcome by increasing the concentration of the agonist drug.

Non-competitive antagonism occurs when the antagonist drug does not compete with the agonist drug for the same receptor binding site, but may bind to a different site on the receptor or interfere with response coupling, and cannot be overcome by increasing the concentration of the agonist drug.

Chemical antagonism results from a direct interaction between the antagonist and agonist drugs, with the antagonist drug binding to or combining with the active drug in solution, rendering it inactive or unavailable to interact with its target receptors.

Pharmacokinetic antagonism occurs when the antagonist drug acts to reduce the effective concentration of the active drug at its site of action, through mechanisms such as reduced absorption, increased metabolic degradation, or increased renal excretion.

Physiological or functional antagonism involves the interaction of two opposing agonist effects in a single biological system, cancelling out each other's effects and typically occurring in the context of opposing drugs eliciting opposing responses by acting on different receptors.

Additivity is a concept that refers to the combined effect of two drugs equaling the algebraic sum of their individual effects.

Synergism or potentiation is a concept where the combined effect of two drugs is greater than the algebraic sum of their individual effects. The synergist may act to increase the concentration of the other drug at its receptor sites.

The GABAA receptor is involved in synergism/potentiation by benzodiazepines.

Potentiation by benzodiazepines refers to the increased responsiveness of the other drug's receptor-effector protein.

Concentration gradient: difference in concentration of a chemical substances between two regions, which creates an electrical gradient across the plasma membrane.

Electrical gradient/membrane potential: the charge difference across the plasma membrane that helps move substances across it.

Passive transport: a method of moving substances across the plasma membrane without the use of energy.

Types of passive transport: simple diffusion, facilitated diffusion.

Simple diffusion: movement of substances across the membrane due to concentration gradients or pressure differences, no energy required.

Facilitated diffusion: movement of polar or charged substances across the membrane through specific carrier proteins.

Ion channels: integral membrane proteins that allow the passage of specific inorganic ions and function as gates to control their movement.

Osmosis: a type of diffusion of water through a semi-permeable membrane, regulated by aquaporins and other water channels.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: the ability of a solution to change the shape or tone of cells through altering their internal water volume.

Membrane potential: the difference in electrical charge across the plasma membrane, which influences the movement of ions and other substances.

Concentration gradient: the difference in concentration of a substance between two regions, which drives the movement of substances across the membrane.

Simple diffusion: a method of passive transport for non-polar substances that move from an area of higher concentration to an area of lower concentration.

Facilitated diffusion: a method of passive transport for polar and charged substances that move through carrier proteins in response to their concentration gradient.

Ion channels: transmembrane proteins that mediate the movement of specific ions through the membrane in a gated manner.

Osmosis: a process of water movement across a semi-permeable membrane in response to a concentration gradient or pressure difference.

Osmolarity: a measure of the total concentration of solute particles in a solution, expressed in units of osmoles per liter.

Tonicity: a property of a solution that determines its ability to alter the shape or volume of cells through the movement of water.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other substances.

Concentration gradient: the difference in concentration of a substance between two regions.

Simple diffusion: a passive process that allows non-polar substances to move across the plasma membrane in response to their concentration gradient.

Facilitated diffusion: a passive process that allows polar and charged substances to move across the plasma membrane through specific carrier proteins.

Ion channels: integral membrane proteins that mediate the passive transport of specific ions through the membrane.

Osmosis: movement of water across a semi-permeable membrane in response to a concentration gradient or pressure difference.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: the ability of a solution to regulate the water balance and shape of cells by altering their internal water volume.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other substances.

Concentration gradient: the difference in concentration of a substance between two regions.

Simple diffusion: a passive process that allows non-polar substances to move across the plasma membrane in response to their concentration gradient.

Facilitated diffusion: a passive process that allows polar and charged substances to move across the plasma membrane with the help of carrier proteins.

Membrane potential: the electric potential difference across the plasma membrane, which influences the movement of ions and other charged particles.

Osmosis: a type of diffusion that allows water to move across a semi-permeable membrane in response to a concentration gradient.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: the ability of a solution to change the shape of cells by altering their internal water balance.

Membrane potential: the electric potential difference across the plasma membrane that drives the active transport of substances against their concentration gradient.

Passive transport: a process that moves substances across the plasma membrane without the use of energy.

Simple diffusion: a passive process that allows non-polar substances to move across the plasma membrane in response to their concentration gradient.

Facilitated diffusion: a passive process that allows polar and charged substances to move across the plasma membrane with the help of carrier proteins.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Osmosis: a process that allows water to move across a semi-permeable membrane in response to a concentration gradient or pressure difference.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: the ability of a solution to change the shape of cells by altering their internal water balance.

Ion channels: integral membrane proteins that allow the passive movement of specific ions across the plasma membrane.

Carrier proteins: transmembrane proteins that facilitate the movement of specific solutes across the plasma membrane against their concentration gradient.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Osmosis: a process of diffusion of water through a semi-permeable membrane in response to a concentration gradient.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: a property of a solution that determines its ability to change the shape of cells through the movement of water.

Simple diffusion: a passive process for the movement of non-polar substances across the plasma membrane in response to concentration gradients.

Facilitated diffusion: a passive process for the movement of polar and charged substances across the plasma membrane with the help of carrier proteins.

Ion channels: integral membrane proteins that mediate the passive movement of specific ions across the plasma membrane.

Osmosis: a type of diffusion that allows water to move across a semi-permeable membrane in response to a concentration gradient.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: a property of a solution that determines its ability to change the shape of cells through the movement of water.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Passive transport: a method of moving substances across the plasma membrane without the use of energy.

Simple diffusion: a passive process for the movement of non-polar substances across the plasma membrane in response to concentration gradients.

Facilitated diffusion: a passive process for the movement of polar and charged substances across the plasma membrane with the help of carrier proteins.

Osmosis: a process of passive water movement across a semi-permeable membrane in response to a concentration gradient.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: a property of a solution that determines its ability to change the shape of cells through the movement of water.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Passive transport: a method of moving substances across the plasma membrane without the consumption of energy.

Simple diffusion: a process for the passive movement of non-polar substances across the plasma membrane in response to concentration gradients.

Facilitated diffusion: a process for the passive movement of polar and charged substances across the plasma membrane with the help of carrier proteins.

Osmosis: a process for the passive movement of water across a semi-permeable membrane in response to a concentration gradient.

Osmolarity: a measure of the total concentration of solute particles in a solution.

Tonicity: a property of a solution that determines its ability to change the shape of cells through the movement of water.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Concentration gradient: the difference in concentration of a substance between two regions.

Simple diffusion: the passive process by which non-polar substances move across the plasma membrane in response to a concentration gradient.

Facilitated diffusion: the passive process by which polar and charged substances move across the plasma membrane with the help of carrier proteins.

Membrane potential: the electric potential difference across the plasma membrane that influences the movement of ions and other charged particles.

Osmosis: the process

The text is about the cellular structure of both Prokaryotic (bacteria) and Eukaryotic cells, including protozoa, plant, and animal cells.

Prokaryotic cells lack a membrane-bound nucleus and have a simpler structure than Eukaryotic cells.

Eukaryotic cells possess a membrane-bound nucleus and have a more complex structure, with organelles, endomembrane system, and a cytoskeleton for support and maintaining cellular structure.

Protozoan cells are part of the Eukaryotic cell group.

The three main parts of a cell are the plasma membrane, cytoplasm (cytosol and organelles), and the nucleus.

The plasma membrane is a phospholipid bilayer, consisting of phospholipids, cholesterol, proteins, and carbohydrates.

Functions of the plasma membrane include acting as a barrier, controlling the entry of materials, receiving signals, and transmitting signals.

Phospholipids are amphipathic, and cholesterol plays a role in maintaining membrane fluidity.

Cholesterol interacts with phospholipids and glycolipids, forming organized clusters that aid in vesicle formation.

Temperature affects the membrane fluidity, and cholesterol has distinct temperature-dependent effects.

Glycolipids are asymmetrically distributed in the membrane, with the carbohydrate groups facing the extracellular fluid and the fatty acid tails being nonpolar.

Integral membrane proteins are closely associated with the membrane lipids and cannot be extracted without disrupting the membrane.

Peripheral membrane proteins are not amphipathic and are located at the membrane surface.

Many membrane proteins are glycoproteins with carbohydrate groups that form the glycocalyx, which acts as a cellular signature.

Cells can be physically joined by various types of junctions, including desmosomes, tight junctions, and gap junctions.

Desmosomes are characterized by dense plaques along the cytoplasmic surface, which are protein anchoring points for cadherins.

Glycolysis is the first stage of cellular respiration, which converts glucose into pyruvate. This process consists of 10 steps, each controlled by specific enzymes.

The preparatory phase of glycolysis requires ATP to begin and produces two molecules of glyceraldehyde 3-phosphate (G3P) from the initial two molecules of Dihydroxyacetone phosphate (DHAP).

In the payoff phase, ATP and NADH are generated from the conversion of phosphoenolpyruvate (PEP) to pyruvate through substrate level phosphorylation.

The final products of glycolysis are two molecules of pyruvate. The entire process occurs in the cytoplasm.

Glycogen and starch serve as feeders for glycolysis. They are broken down and enter the preparatory stage of glycolysis, contributing to the overall ATP generation.

Lactose intolerant individuals cannot convert lactose into glucose due to a lack or lower level of the enzyme lactase. As a result, the undigested lactose is fermented by gut bacteria, which leads to symptoms like gas, bloating, pain, and diarrhea.

In the absence of oxygen, pyruvate is reduced to lactic acid, and the transferred electrons oxidize NADH back to NAD+. This reaction is catalyzed by the enzyme lactate dehydrogenase (LDH). High levels of lactate can lead to muscle cramps, pain, and potentially life-threatening conditions.

The Cori cycle (also known as the lactic acid cycle) describes the process by which lactate produced during anaerobic glycolysis is transported to the liver, where it is converted back to glucose. This process requires ATP, and the resulting glucose can be either used or stored as glycogen.

The heart and brain must be continuously supplied with fuel and cannot be starved. In the absence of glucose, pyruvate can be converted to glucose through the process of gluconeogenesis, which occurs in the liver. This process will be covered more in diabetes lectures.

In the presence of oxygen, pyruvate is converted to acetyl CoA and enters the next stage of metabolism, the citric acid cycle, which occurs in the mitochondria. Pyruvate moves through the mitochondrial membrane to encounter the enzyme pyruvate dehydrogenase (PDH).

The citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid cycle, is the next stage of metabolism where acetyl CoA derived from pyruvate is further broken down. This process generates ATP, NADH, and FADH2. The cycle is named after Hans Krebs, who discovered it in the 1930s.

One molecule of glucose entering the glycolysis process will eventually yield a net gain of 38 ATP molecules (2 molecules generated during glycolysis, 32 ATP generated during the citric acid cycle, and 4 ATP generated through oxidative phosphorylation) and 2 molecules of CO2.

Glycolysis is the first stage of cellular respiration, which converts glucose into pyruvate. This process consists of 10 steps, each controlled by specific enzymes.

The preparatory phase of glycolysis requires ATP to begin and produces two molecules of glyceraldehyde 3-phosphate (G3P) from the initial two molecules of Dihydroxyacetone phosphate (DHAP).

In the payoff phase, ATP and NADH are generated from the conversion of phosphoenolpyruvate (PEP) to pyruvate through substrate level phosphorylation.

The final products of glycolysis are two molecules of pyruvate. The entire process occurs in the cytoplasm.

Glycogen and starch serve as feeders for glycolysis. They are broken down and enter the preparatory stage of glycolysis, contributing to the overall ATP generation.

Lactose intolerant individuals cannot convert lactose into glucose due to a lack or lower level of the enzyme lactase. As a result, the undigested lactose is fermented by gut bacteria, which leads to symptoms like gas, bloating, pain, and diarrhea.

In the absence of oxygen, pyruvate is reduced to lactic acid, and the transferred electrons oxidize NADH back to NAD+. This reaction is catalyzed by the enzyme lactate dehydrogenase (LDH). High levels of lactate can lead to muscle cramps, pain, and potentially life-threatening conditions.

The Cori cycle (also known as the lactic acid cycle) describes the process by which lactate produced during anaerobic glycolysis is transported to the liver, where it is converted back to glucose. This process requires ATP, and the resulting glucose can be either used or stored as glycogen.

The heart and brain must be continuously supplied with fuel and cannot be starved. In the absence of glucose, pyruvate can be converted to glucose through the process of gluconeogenesis, which occurs in the liver. This process will be covered more in diabetes lectures.

In the presence of oxygen, pyruvate is converted to acetyl CoA and enters the next stage of metabolism, the citric acid cycle, which occurs in the mitochondria. Pyruvate moves through the mitochondrial membrane to encounter the enzyme pyruvate dehydrogenase (PDH).

The citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid cycle, is the next stage of metabolism where acetyl CoA derived from pyruvate is further broken down. This process generates ATP, NADH, and FADH2. The cycle is named after Hans Krebs, who discovered it in the 1930s.

One molecule of glucose entering the glycolysis process will eventually yield a net gain of 38 ATP molecules (2 molecules generated during glycolysis, 32 ATP generated during the citric acid cycle, and 4 ATP generated through oxidative phosphorylation) and 2 molecules of CO2.