METABOLISM -Introduction- Serkan SAYINER, DVM PhD. Assist. Prof.

Transcription

1 METABOLISM -Introduction- Serkan SAYINER, DVM PhD. Assist. Prof. Near East University, Faculty of Veterinary Medicine, Department of Biochemistry

2 Overview Living organisms need the chemicals to renew themselves and to develop and reproduce. This is because, all organisms are formed from the chemical substances. These chemical substances can be organic such as carbohydrates, lipids protein, or can be water and inorganic elements such as Ca, P, Fe, S. For example, skin is formed from water, proteins, lipids and inorganic materials, beside this cell membranes are formed from lipids and proteins. The molecules that make up the organism either participate in the structure of the organism or participate in the functions that provide the formation and continuity of the structure. Once ingested and absorbed molecules enter the cell, they participate in various biochemical reactions.

3 Definitions METABOLISM: It is the chemical reactions that occur within the tissues and cells of a living organism and enables the production and continuity of living matter. ANABOLISM: To synthesize the compounds of structural or functional molecules from matters taken from food or inside the organism. It is also called the orientation of the constructions of metabolic reactions. CATABOLISM: Fragmentation of molecules synthesized by the organism or cells imported into the cell, therefore the it can also called degradation of the metabolic processess. Anabolism + Catabolism = METABOLISM

4 Definitions Exergonic Reactions: Some of the reactions occurring in the body are energizing. This reactions are called exergonic reactions. Endergonic Reactions: Some of the reactions occurring in the body are energy receiving. This reactions are called endorgonic reactions. Intermediate metabolism: The metabolic processes within cells and tissues in the organism referred to by the term intermediary metabolism. In other words, the set of reactions within the cells is called intermediate metabolism.

5 Definitions Foodstuffs entering the body express changes only after they are absorbed in the digestive tract. The anabolic and catabolic reactions in the intermediate metabolism develop in steps, that is, the formation of a number of intermediates. In other words, the reaction takes place in the form of the initial substance reaching the final product through intermediates. Intermediate metabolic substances in this type of reactions are called metabolites.

6 Precursor End- Product Intermediate Metabolite Intermediate Metabolite Intermediate Metabolite Metabolites (Intermediate metabolik substances)

7 Reactions of Metabolism There is a wide variety of metabolic reactions in the organism that occurs. It is possible to collect them under 3 groups. Hydrolysis and Condensation Phosphate transport Biological oxidations

8 Reactions of Metabolism CONDENSATION A reaction in which two or more molecules combine to form a larger molecule, with the simultaneous loss of a small molecule such as water Glycoside bond (between two monosaccharide molecules in combination with an ether linkage), Peptide bond (between two amino acids), ester bond (between glycerol and fatty acids) are some examples. Condensation is an endergonic reaction that energy is used.

9 Reactions of Metabolism HYDROLYSIS It is a reaction involving the breaking of a bond in a molecule using water. The reaction mainly occurs between an ion and water molecules and often changes the ph of a solution. Polysaccharides with amylase, degradation of proteins with pepsin in the gastrointestinal tract, the cleavage of triglycerides to glycerol and fatty acids by lipase are some examples of hydrolysis events occurring in the body. They are exergonic reactions that release energy. 1-4 kcal of energy per molecule released. Hydrolysis events that take place under digestive enzymes in the organism and the body's temperature, can be formed by boiling with concentrated acid and alkaline in vitro.

10 Sucrase

11 Reactions of Metabolism PHOSPHATE TRANSPORT In organism, many molecules, especially carbohydrates, need to be phosphorylated, i.e. phosphate esters, to be able to enter into the reactions. In this task, phosphate carriers are loaded and phosphate residues are given to the required molecules. Phosphate carriers are classified in 2 groups according to the number of phosphate residues they contain. 1. One phosphate residue carriers 2. Multiple phosphate residues carriers

12 Reactions of Metabolism 1. One phosphate residue carriers Molecules that carry enol, carboxyl, hydroxyl or an amino group change its H atom with a phosphate residue (H 2 PO 3- ). 2. Multiple phosphate residues carriers Examples of this group may be adenosine diphosphate (ADP) and adenosine triphosphate (ATP). These materials can be formed by replacing 1 hydrogen from an alcohol group of a pentose nucleotide and receiving 2 or 3 phosphate residue.

13 Reactions of Metabolism PHOSPHATE BONDS AND ENERGY Some molecules carrying a phosphate residue have weak phosphate bonds and some have resistant bonds. Resistant phosphate bonds have weaker energy. Most of them are phosphate esters and it is possible to break down with phosphatase enzymes in the organism and with aqueous acids and alkalis in vitro. Degradation of Glucose-6-phosphate (G-6-P) to phosphate and glucose releases low energy (3.3 kcal.

14 Reactions of Metabolism Weak phosphate bonds are bonds that break down and give high energy. Acyl sulfates, enol phosphates, adenosine triphosphate molecule are carrying this kind of phosphate bonds. They are destroyed with special phosphatase enzymes in biological reactions, 7-13 kcal of energy is released. Thats why these phosphate compounds are also called high-energy phosphate compounds. For example, a phosphate and the ADP revealed with the degradation of the ATP and the 7 kcal energy occurs.

15 Phosphate Bonds And Energy Phosphate inculing molecules Bond type Reaction Kcal Glucose-6-phosphate Ester G-6-P Gli + P - 3,3 ATP Phosphoanhydride ATP ADP + P - 7,0 ATP Phosphoanhydride ATP AMP + P + P - 8,6 Phosphoenolpyruvate Enolphosphate PEP Pyruvate + P - 13,0 Creatin phospahte Phosphamide Creatin-P Creatin +P - 10,2

16 Reactions of Metabolism All high-energy phosphate compounds serve as the phosphate donor. The hydrolysis of such phosphate compounds leads to energy output. Among these, however, ATP, in particular, provides both the necessary phosphate and energy for the destruction of another molecule. Phosphate and energy transport in the organism is under the control of phosphokinase enzymes.

17 Reactions of Metabolism BIOLOGICAL OXIDATIONS (Oxidation and reduction events) Transition of electrons from one atom or molecule to another referred to as redox reaction (Redox: e - transfer). OXIDATION: It is the loss of electrons or an increase in oxidation state by a molecule, atom, or ion. REDUCTION: It is the gain of electrons or a decrease in oxidation state by a molecule, atom, or ion. Hydrogen ions are also seperated from the organic molecule with the electrons. Thats why the simplest type of an oxidation is called dehydrogenation. In organism, enzymes are also oxidized or reduced.

18 Reactions of Metabolism e - A (reducing) e - A (oxidized) B (oxidizing) e - e - B (Reduced)

19 Mechanism of Biological Oxidations The most important electron donors in the organism are hydrogen atoms of organic molecules (e.g. glucose, fatty acids). The hydrogen atom consists of an H + and an e -. The most important electron receivers are the oxygen molecule of air (O 2 ).

20 Mechanism of Biological Oxidations Biological oxidizations are the transport of H ions and electrons in these organic materials to oxygen. The reactions are formed in steps rather than in a single reaction. In these steps, H ions and electrons in organic materials are transported by oxidationreduction enzymes (redox enzymes). Reducing equivalent refers to any of a number of chemical species which transfer the equivalent of one electron in redox reactions. Redox enzymes are essential for this transfer. They are transported either directly or indirectly to the oxygen.

21 Mechanism of Biological Oxidations Direct biologic oxidations in body occur in very small amounts. The enzymes involved in this case are Oxidase. Indirect biologic oxidations in body occurs in great amounts. dehydrogenases.

22 Mechanism of Biological Oxidations Indirect Biologic Oxidations In this type of biological oxidation, H ions and electrons are taken from the organic molecules through enzymes and transported as a series of enzymes as oxygen. In this case, dehydrogenases are called respiratory enzymes. The active moieties (i.e. the moieties carrying hydrogen and electrons from organic molecules) carrying the reduction residues of these enzymes are the coenzymes and the coenzymes are grouped into four groups according to their active groups.

23 Mechanism of Biological Oxidations 1. PYRIDINE NUCLEOTIDE ENZYMES The effective group is nicotinic acid amide. The full name of the coenzyme is nicotinamide adenine dinucleotide (NAD). There are 2 phosphoric acids in the structure. In the third entry, NADP + (nicotinamide adenine dinucleotide phosphate) occurs. NAD and NADP + are reduced by receiving electrons and H ions, becoming NADH+H + and NADPH. Enzymes with coenzyme NAD are particularly involved in carbohydrate metabolism, metabolic pathways such as glycolysis and TCA cycle, and in the mitochondrial respiratory chain.

24 Mechanism of Biological Oxidations 2. FLAVIN CONTAINING ENZYMES The effective group is riboflavin (Vitamin B 2 ), its dimethylisoalloxazine group. The full name is flavin adenine dinucleotide (FAD). Reduced state is FADH 2. FAD is tightly bound to a specific apoenzymes. In the respiratory chain, the electrons and hydrogen taken from pyridine enzymes and organic substances are transferred to the quinone enzymes (Q) by FAD.

25 Mechanism of Biological Oxidations 3. ENZYMES WITH QUINONE (COENZYME Q 10 ) Effective group is quinone. It carries 10 isoprene as a side chain. It is reduced to hydroquinone after gaining 2H + and 2e -. There is a close relationship with cytochromes involved in the biological oxidation chain. 2H + and 2e - from Flavin containing enzymes causes reduction of its and these are given to cytochromes (iron containing enzymes).

26 Mechanism of Biological Oxidations 4.ENZYMES CONTAINING IRON Active group is iron (Fe). It is located in porphine skeleton. Thereby forming a coenzyme. These coenzymes, which are found in porphyrin structures, bind very tightly to various specific proteins, bringing up various ferric enzymes. These enzymes are mainly cytochromes and cytochrome oxidases.

27 Mechanism of Biological Oxidations This coenzyme function is based on the fact that only the electrons exchange and give rise to changes in the iron valence. Trivalent iron is reduced to divalent iron. There are three types of cytochromes; b1, c1 and c cytochromes. They transfer the electrons they receive from Koenzim Q to one another.

28 Mechanism of Biological Oxidations The electron donor is oxidized and acceptor is reduced. Reduced cytochrome c gives its electrons to cytochrome oxidases and is self-oxidized again. There are two types of cytochrome oxidases; Cytochrome a and cytochrome a 3. Cytochrome c

29 Mechanism of Biological Oxidations Cytochrome oxidase a 3 takes electrons from the cytochrome c and reduced. Reduced cytochrome oxidase a 3 gives electrons to O 2 and turns it to oxygen ions. The oxygen ion also reacts with the two hydrogen atoms in the environment, so that water is synthesized. The synthesis of endogenous water in the organism occurs in this way.

30 The function of the Respiratory Chain Much of the biological oxidation occurs when multiple oxidationreduction events complement each other and are arranged as rings of a chain. At the end of this chain, there is an oxidized substance formed by the direct effect of a special dehydrogenase enzyme by activating the hydrogen from the organic substances and a molecular oxygen at the other end. Between the two ends a special alignment of hydrogen and electron acceptor and carrier enzymes is observed. This is called the electron transport chain or the respiratory chain. This chain can start from the NAD as well as from the FAD.

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32 The amount of energy and production place in the respiratory chain Overall energy is revealed at the end of oxidation. The chemical entering the reaction goes down to a level lower than the high energy level in the system. The same phenomenon is seen in the respiratory chain. During the 2 H + and 2 e-transport, there is sufficient energy production to form a high-energy bond. The energy released is moved adenosine diphosphate 'e (ADP) with an inorganic phosphate. ADP uses the energy and phosphate linking constitute high energy adenosine triphosphate (ATP).

33 The amount of energy and formation place in the respiratory chain If chain starts from a dehydrogenase with NAD and is oxidased, 3 mol ATP is synthesized. If chain starts from a dehydrogenase with FAD and is oxidased, 2 mol ATP is synthesized.

34 Importance of Biological Oxidation One of the events that continue to occur in organism is biological oxidations. These events provide the necessary energy for endergonic chemical reactions occurring in the body, as well as the emergence of many new substances necessary for the body during oxidation and degradation of a substance.

35 Importance of Biological Oxidation 700 kcal for 1 mole of glucose in biological oxidation occurs. 1 mol ATP stores 7-8 kcal. The energy stored in the form of ATP, Is used in the formation and maintenance of body temperature. Provides to maintain peptide bonds, glycoside bond and many reaction events. Is used to maintain active contraction of the muscles and cell membrane permeability (active transport) and secretion events.

36 The reaction cycles of metabolism A metabolic pathway is a linked series of chemical reactions occurring within a cell. Some metabolic pathways flow in a 'cycle' wherein each component of the cycle is a substrate for the subsequent reaction in the cycle. The sequence of chain reactions starting from a basic substance and returning to that basic substance at the end of ongoing reactions is called the metabolic cycle or reaction cycle. For example: TCA cycle or Krebs Cycle

37 TCA Cycle or Krebs Cycle or Citric acid cycle

38 Locations of Metabolic Reactions in the Cell Nucleus Transfer and replication of hereditary molecules (DNA and RNA), hydrolysis and synthesis of nucleic acids, proteins (transcription). Mitocondria Biological oxidations, TCA cycle, ATP synthesis. Ribosomes Protein biosynthesis (translation).

39 Locations of Metabolic Reactions in the Cell Endoplasmic Reticulums Folding and transport proteins. Lysosomes Hydrolysis of nucleic acids and proteins proteinase. It contains many proteolytic enzymes such as RNase, phosphatases, glycosidases. Cytoplasm Glycolysis, destruction of proteins, destruction of fat, glycogen breakdown, biosynthesis of fatty acids.

40 Question 1... İs a reaction in which two or more molecules combine to form a larger molecule, with the simultaneous loss of a small molecule such as water. a. Condensation b. Hydrolysis c. Oxidation d. Dehydrogenation e. Reduction Answer: a

41 Question 2 Which of the following molecules carry multiple phosphate residue? a. PEP b. G-6-P c. Creatin Phosphate d. ATP e. AMP Answer: d

42 Question 3 Which of the following is not a coenzyme of respiratory chain? a. NAD b. FAD c. Phosphofructokinase d. Cytocrom a e. Q 10 Answer: c

43 Any Questions?

44 References Ası T Tablolarla Biyokimya II. Nobel Tıp Kitapları Dağıtımı Sözbilir Bayşu N, Bayşu N Biyokimya. Güneş Kitabevi

45 Next topic is Carbohydrate Metabolism

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