Hello everyone. Welcome back to my Coursera class, Biochemical Principles of Energy Metabolism. In the previous session three for week two is about carbohydrate digestion. So, so far, we've reached the step of carbohydrate, let's say, glucose degradation throughout those polymer, glucose polymer degraded like strout amylase actions and now finally, glucose monomers produced. And you've faced many different types of enzymes. So obviously, next step is how glucose can be absorbed into our body. So instead of explaining the glucose or carbohydrate absorption process, I'm going to have a review session for enzyme. So what is enzyme? I think you're going to see many, many, many different types of enzymes throughout this class. So it's going to be very, very important for you to have clear and solid foundation for enzyme function. So, what is enzyme? Enzyme is a substance that can act as a catalyst. In particular, a catalyst in the living organisms, that is called enzyme. So what's the main point or main action of enzyme in biochemical reaction? Just to look at this graph, and let's say that this is a simple biochemical reaction, carbon dioxide and water, product is bicarbonate. So, free energy reactants like these high end products, like this low, and throughout those reactions depending on the presence of an enzyme, the rate of this reaction can be hugely changed. The point is, without enzyme, this reactant should go through this high energy status and then relieved into product. So without enzyme, this amount of energy change throughout this chemical transformation, is called activation energy, activation energy is that high. The thing is, under the condition of the support of enzyme, this activation energy can be lowered. So that means, by reducing the activation energy, that means the enzymes can increase, dramatically increase, the rate of biochemical reaction. So, there're over 5,000 different types of biochemical reactions available in the living system and enzymes are the major player in terms of trigger and facilitate the biochemical reactions. So as you can see this diagram, enzyme binds to substrate, an enzyme substrate complex. So this enzyme assist and facilitate the biochemical transformation of substrate into product. And this catalytic step, I'm not going to go into very detail, the Kcat catalytic power, Kcat, can be hugely increased. And most enzymes are proteins, but some few enzymes are going to be RNA-based. And this is quite important because when the biochemist and biologist for the first time identified RNA-based enzyme and we are really are surprised, and then this is another price topic of the cuticle. An enzyme, their catalytic activity, how can be regulated? There are many important factors, I'm going to list up one by one. First one is temperature. And you know that, right? That temperature overall can increase the rate of reaction. Why is that? When temperature rises, the substrate molecules can have more kinetic energy, and that increases the chances of a successful molecular interactions, and finally, the rate of biochemical reactions. The thing is, enzymes catalytic activity requires optimal temperature, and our body temperature is 37.5 degrees in celsius, and that's the optimal temperature for the enzymes in our cells. And this is diagram, around 37 degrees is the highest activity of enzymes. The second factor is pH, another word, acidity. So each enzyme, protein based enzyme or even RNA whatever, they can operate in a small range of pH, and there is optimal pH conditions for the best performance of enzyme. Why is that? Because the pH acidity, that means protein concentration can affect the molecular interactions around enzyme and substrate, therefore, enzyme functions can be changed. So some enzymes, this is pH 7, pH 0 and pH 14, some enzymes are really active around pH 7, some enzymes are really active on the acidic condition or in basic condition. Some examples over here, like amylase, we studied in the previous session. Amylase can degrade carbohydrate into small pieces but the optimal pH is around 7. And what about maltase? Intestinal maltase also they can do their own job around near neutral pH. But in the case of pepsin, pepsin is the enzyme for protein degradation. Protein degradation into small amino acid or smaller chain, okay? And this pepsin degradation occurs inside your stomach. And in the stomach there is hydrochloric acid, and that very aesthetic condition pepsin can be fully activated, and can function integrating protein nutrient into amino acid or a smaller polypeptide. Number three is cofactor. Some enzymes require coenzymes. That means a small organic compound or mineral cofactors. Zinc, sodium, or potassium, those kind of mineral-based cofactors. When those cofactors or coenzymes they directly bind to the active side of the target enzyme, then that enzyme can be fully activated. And these small organic molecules for coenzymes are indeed many cases derived from vitamins. Ultimately, that means from the diet. And other coenzymes or cofactors like metals, many metals, also supposed to be supplied from the environment, I mean from the food. So, again, the concept of cofactor is some enzymes absolutely require cofactor. Maybe some organic molecules or some minerals, and then form a holoenzyme and this is functional. And one, this protein structure diagram, this is Carbon and Hydroid. You don't need to remember the structure of this enzyme. The thing is, in the middle, you are looking at symbol or ball, this is zinc. Without zinc, this enzyme cannot be active. That cofactor is an absolute factor for full activity of and target enzyme. Number four is modification. So, protein is modified. The nature of modification is Covalent modification. When protein based enzymes are chemically modified, their activity can be changed. Then modification can occur on top of specific amino acids side chain in the middle or maybe extreme C-terminus or extreme N- terminus. But the point is, when the protein enzyme is chemically modified through a covalent bond, that is called Post-translation modification. Throughout this modification, this enzyme activity can be increased or decreased. This is another layer of enzyme activity regulation. So, best well known example is phosphorylation. When enzyme is phosphorylated, then enzyme function can be regulated. So, this isn't Nobel Prize topic diagram. So, there is an enzyme glycol and phosphorylase. When this enzyme is phosphate attached throughout those phosphate covalent attachment, covalent modification, then this enzyme activity can be fully manifested in the active state. So, this enzyme activity can be regulated by simple phosphate attachment or detachment, phosphatase or kinase. And this event, biochemical event is one of the key features in terms of the glycogen reutilization for energy sources. And there are different types of proteins from modification are identified. And among those four different factors: temperature, pH, cofactors, and post-translational modification can regulate enzyme activity. So, in that sense, I'm going to introduce one medical symptom called the Lactose Intolerance. We are looking at the World Map showing that many human beings are affected by this symptom called Lactose Intolerance. So, basically, Lactose Intolerance is caused by the reduced capacity to digest lactose. In particular, lactose is highly enriched in our dairy products like milk. So, this lactase is very, very important intestinal digestive enzyme. When this lactase is not optimally expressed in function, lactose cannot be degraded into glucose and lactose. In that case, abdominal pain, and bloating, and in severe cases diarrhea, and nausea can be developed. So, that's why some people consume lactose free or low lactose dairy product. And in some severe cases, the medical doctors prescribe lactase tablets that enzyme can be directly used to digest, to fully digest the lactose ingredient from the dairy product. So, enzymes sometimes nicely inhibited and those inhibitors are basically the biochemical basis of drug development. There are two types of enzyme inhibitors available. Number one is competitive inhibitor. The point is, okay, enzyme bind, can bind to a substrate and this area is called active site. When some inhibitory molecules directly compete with the substrate in terms of taking this active side position that is compared to a competitive inhibitor. But on the other case, noncompetitive inhibitor does not compare this active site with substrate, rather there is another distinct area of inhibitor binding site. The thing is, when this noncompetitive inhibitor can bind to target enzyme and this enzyme to structure and function or the substrate binding can be severely negatively affected. Thus the noncompetitive inhibitor treatment can reduce the maximal catalytic activity of target enzyme. So, today's session is about enzyme. Conceptually is very clear. So biocatalyst and absolutely essential for metabolic reactions in terms of reducing activation energy by elevating catalytic steps by forming a complex substrate.
