The nature of chemical reactions in cells

What do cells do? All cells need to: obtain nutrients grow maintain and repair themselves provide energy for movement and metabolism and eliminate wastes. These activities require the production of a variety of biological molecules (biomolecules), which are then assembled into new organelles or used for repair and maintenance of cells. Particular proteins called enzymes control the synthesis of these various biomolecules and many other cellular processes, such as cellular respiration, which keep the cells alive.

Metabolism Is the overall chemical activity of cells. Includes the synthesis of organic molecules, various energy transforming and recycling processes, and the breakdown of unwanted substances. These chemical reactions involve hundreds of enzymes working in ‘chains’, where the product of one reaction is the substrate for the next enzyme. A substrate is the molecule on which an enzyme acts. These chains of reactions are known as metabolic pathways (also biochemical pathways). There are more than 1000 enzymes inside each cell, and many different reactions may be taking place simultaneously.

Metabolic reactions A + B ↔ C + D A reaction occurs between reactants when chemical bonds are broken and the atoms recombine to produce a new substance or substances (referred to as products). A + B ↔ C + D For A and B to react they need to have sufficient energy before collisions between them will give rise to the products C and D. The amount of energy needed to initiate the reaction is referred to as the activation energy.

Energy in reactions Adenosine triphosphate (ATP) is the universal energy carrier for cells. Reactions that require energy input are said to be endergonic. Reactions that release energy are said to be exergonic. Anabolic reactions are those in which complex molecules are built up from simpler molecules. They are always endergonic. Catabolic reactions are those in which complex molecules are broken down into simpler molecules. They are always exergonic.

How does ATP carry energy? ATP is a coenzyme that consists of three phosphate groups attached to an adenosine molecule. The removal of the third or terminal phosphate group by hydrolysis results in the release of energy. This reaction is catalysed by the enzyme ATPase. Once ATP has released its energy, it becomes ADP (adenosine diphosphate). ADP is a low energy molecule that can be recharged by adding a phosphate in a process known as phosphorylation. The phosphorylation reaction requires energy, which is supplied by exergonic reactions occurring within the cell.

Interrelationship between exergonic and endergonic reactions Thousands of metabolic reactions occur continually within a cell. Some are endergonic, some are exergonic. ATP/ADP provides the cell with an efficient linking of energy-yielding processes to energy-requiring processes within the cell.

Metabolic pathways Most metabolic reactions in cells occur in a series of steps, called a metabolic pathway. This ensures that energy requirements can be controlled and that the reaction proceeds in the direction of product formation. All chemical reactions are reversible under certain conditions – if a product is not removed a reaction may be reversed. To prevent this biochemical reactions proceed through a series of steps in which the product of one step becomes the reactant for the next step. This ensures that products are continually removed. Each step in a biochemical pathway is regulated by a specific enzyme.

What are enzymes? Enzymes are protein catalysts. They reduce the activation energy required to begin the reactions they catalyse and as a result increase the reaction rate. Without enzymes, metabolism would be so slow at body temperature that insufficient energy would be available to maintain life!!!! Many enzymes are intracellular — they are used within the cells that produce them. These include the enzymes involved in cellular respiration and photosynthesis. Other enzymes, such as digestive enzymes, are extracellular — they act outside the cells that produce them. Handy hint: Names of enzymes normally end in ‘-ase’. Those that don’t tend to be enzymes that have been known for a long time.

Enzymes lower activation energy

Catalase: an example of enzyme power Catalase is found in several organs and tissues, including the liver. Its job is to speed up the decomposition of hydrogen peroxide (H2O2). H2O2  H2O + O2 Adding Fe3+ ions (an inorganic catalyst) makes the reaction 30,000 times faster. Adding catalase makes the reaction about 100,000,000 times faster.

Characteristics of enzymes Only a small amount of enzyme is needed to do a big job. They are not used up in the reaction. An enzyme doesn’t change the direction of the reaction, but does speed up the reaction. An enzyme won’t change the final amount of product formed. Enzymes are very specific to their substrate. This is an example of molecular specificity.

Enzymes and their substrates The specificity of enzymes for their substrates is related to the three-dimensional structure of the molecules. The active site on an enzyme is the part of the molecule that interacts with the substrate.

How enzymes bind their substrates The active site of an enzyme has a shape that complements the shape of the binding site of the substrate; that is, they ‘fit together’ like pieces of a jigsaw puzzle. Two models exist to describe the mechanism of an enzyme binding with it’s substrate. These are: Lock and key model Induced fit model has been refer red

Models of enzyme/substrate interactions Lock and Key Model Reactants fit tightly into the 3D shape of the enzyme’s active site. Induced Fit Model The actual interaction between substrate and enzyme changes the shape of the enzyme to produce the right fit.

Cofactors and coenzymes Although many enzymes are pure proteins, folded so that they have a specific active site, many enzymes require the presence of other factors as well as the protein part before they act. These non-protein parts are called cofactors or coenzymes depending on their chemical composition. Cofactors are inorganic molecules, and include metallic ions such as iron, calcium, copper, zinc, potassium and magnesium. Coenzymes are organic molecules that are often derived from vitamins. They assist catalysis by binding to enzymes or by functioning as carriers of electrons and protons.

Important Coenzymes COENZYME ABBREVIATION FUNCTION Loaded form Unloaded Adenosine triphosphate ATP ADP Energy transfer Nicotine adenine dinucleotide (based on the vitamin niacin) NADH NAD+ Transfer of electrons and protons Nicotine adenine dinucleotide phosphate NADPH NADP+ Flavine adenine dinucleotide (based on the vitamin B12) FADH2 FAD

Factors that influence enzyme activity Factors that influence enzyme activity include: pH Temperature Inhibitors Enzyme concentration Substrate concentration Cofactors and coenzymes

pH affects enzyme activity The pH scale is 1–14, where 1 is very acidic, 14 is very basic, 7 is neutral. The optimum pH for an enzyme is that at which the enzyme shows maximal activity. Each enzyme has an optimum pH (enzymes are very sensitive to pH). Changing pH affects enzyme function because hydrogen bonds break, and therefore the 3D shape of the enzyme changes.

pH affects enzyme activity Different enzymes have different optimum pH values. For example, in the stomach the enzyme pepsin has a low optimum pH, so the stomach produces acid to maintain this low pH. The enzymes of the pancreas need a higher pH to work.

Temperature affects enzyme activity Warming increases the rate of most chemical reactions, including enzyme catalysed reactions. Extra heat energy is taken up by molecules so they move faster. This increases the rate of interaction between substrate and enzyme. Lower temperatures meant that molecules move more slowly. This decreases the rate of interaction between substrate and enzyme. Although temperatures either side of the optimum temperature will decrease enzyme activity, extremes of heat and cold have different effects.

Temperature affects enzyme activity Most enzymes have an optimum temperature range, which is the temperature at which the enzyme’s catalytic activity is greatest. Temperatures outside the optimum temperature range will decrease enzyme activity.

Temperature affects enzyme activity The rate of enzyme activity increases with increasing temperature until the enzyme begins to denature or break down. The temperature at which denaturation begins is referred to as the critical temperature of an enzyme. Denaturation means that the tertiary structure of the protein is permanently changed and cooling it back down again won’t restore the enzyme’s function. In contrast, enzymes are not denatured when it is too cold. Enzymes that are inactivated because of low temperatures become active again when the temperature is returned to normal.

Inhibitors An inhibitor is any chemical that changes the shape of the active site of the enzyme so that it has a lower affinity for substrate. Inhibitors may be reversible or irreversible. Reversible inhibitors are used to control enzyme activity as they only temporarily deactivate enzymes. Heavy metals such as lead, mercury and arsenic are toxic because they are irreversible inhibitors of enzymes. Inhibition may be competitive, non-competitive or allosteric.

Different types of inhibitors Competitive inhibitors Inhibitory molecule competes with the substrate for the active site. Slow down enzyme activity by blocking substrate binding to active site. Non-competitive inhibitors Allow the substrate to bind to the active site. Slow down enzyme activity by binding elsewhere to enzyme. Allosteric inhibitors Do not compete for the active site. Bind elsewhere to enzyme in a manner that causes a change in the conformation (shape) of the active site such that the substrate will no longer fit.

Enzyme concentration The rate of enzyme activity increases with increasing enzyme concentration. Increased enzyme concentration will increase the rate of reaction. Increased enzyme concentration will not increase the amount of product formed.

Substrate concentration Increased substrate concentration will increase the amount of product formed. Increased substrate concentration will increase the rate of reaction up to the point when the enzyme is saturated with substrate.

Enzymes and disease Several inherited diseases (often referred to as ‘inborn errors of metabolism’) involve an inability to manufacture a particular enzyme required to break down substances that are normally part of the diet. Examples include: galactosaemia, lactose intolerance and phenylketonuria. Galactosaemia due to an error (mutation) in the gene responsible for producing one of the enzymes needed to convert galactose to glucose-1-phosphate. Galactose accumulates in the blood and present in their urine. The liver becomes enlarged, cataracts form, growth is slow and mental development is retarded. Sufferers who are left untreated do not often live beyond infancy. The treatment for galactosaemia is simple and largely successful if it is commenced soon enough. All foods containing galactose, chiefly milk and milk pro ducts, must be excluded from the diet.

Two very important chemical reactions The importance of enzymes, and the linkage between endergonic and exergonic reactions is highlighted when we study photosynthesis and cellular respiration. Photosynthesis is an endergonic reaction. Cellular respiration is an exergonic reaction.