Good biochemistry summary, Summaries of Bioethics

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ENERGY PRODUCTION I:

GLYCOLYSIS

Dr. Öğr. Üyesi Derya CANSIZ

• As a result of the complete oxidation of glucose, CO 2 and H 2 O are obtained.
• The hydrogens separated from the food are formed with the oxygen of air.
• This reaction sequence takes place in a very special structure and special enzyme system (ETS) in the mitochondria.
• The high temperature that occurs during the formation of this water, called endogenous water, allows the combination of ADP and Pi in the mitochondrial environment.
• Thus, the heat energy generated is stored in the form of ATP.
• This event (oxidation of glucose) takes place in all tissues.

• However, depending on the O2 concentration in the cell environment, the reaction steps and related enzymes change depending on whether it occurs in either anaerobic (without oxygen) or aerobic (with oxygen) environment.
• Oxidation that occurs in the absence of oxygen is called glycolysis or anaerobic oxidation , that is, oxidation without oxygen.
• The citric acid cycle works in the oxidation that occurs in the oxygen environment.
• In this oxidation stage, the reaction in glycolysis continues until the formation of pyruvic acid.

• Later, pyruvic acid is converted to acetyl CoA and enters the citric acid cycle. So it goes a long way to enter the citric acid cycle.
• Therefore, the oxidation in which the citric acid cycle is involved is called indirect oxidation or aerobic oxidation with oxygen.
• Another oxidation of glucose is the direct oxidation or Pentose phosphate pathway.
• This pathway is also known as the phosphogluconate pathway. The reason why this pathway is called direct oxidation is that the oxidation steps take place in the first stages of the reaction.

• Phosphorylation
• Conversion of hexoses to trioses
• Oxidation stages
• Formation of lactic acid

• The phosphorylation step is necessary for glycolysis and other sugars.
• Because glucose and other sugars are phosphorylated
• Then it turns into active form and takes part in metabolic reactions.
• While the entry of sugars into the cell is accelerated by insulin , it is slowed down by growth hormone (GH) and adrenocorticoids. Glukozun aktif formu GH Adrenocorticoids Hexokinase Anaerobic oxidation
• In the anaerobic system, 2 molecules lactic acid are formed from glucose. No oxygen is used in this reaction.
• Lactic acid is used for re-synthesis of glucose by another metabolic pathway. Isomerase

• NADH is used because there will be a reduction reaction when lactic acid is formed.
• In this case, the ATP gain from NADH is zero.
• Because the NADH formed during the oxidation in the upper stage of glycolysis will be used in the following reduction reaction.

• 1,3 diphosphoglyceric acid, a product of oxidation reaction, is a high-energy phosphate compound.
• ATP is produced from this high-energy phosphate compound by the enzyme phosphoglycerokinase.
• This ATP is ATP obtained at the substrate level.
• ATP is obtained in large quantities by reduced nucleotides (NADH, FADH) that go to the mitochondria at the end of aerobic respiration.
• Here, the high-energy ATP molecule is obtained in a different way.

Lactate formation in muscle Gluconeogenesis in the liver

• The direction of the LDH reaction seen in the figures above depends on the intracellular concentration of pyruvate and lactate and the NADH/NAD ratio in the cell.
• For example, the liver and heart have a lower NADH/NAD ratio than muscle in exercise. These tissues oxidize lactate to pyruvate (NADH is gained).
• LAKTAT formation (Anaerobic Glycolysis) gives a chance to life for erythrocytes without mitochondria.
• It has to survive to carry oxygen to the erythrocytes to other cells and also to form 2,3 diphosphoglycerate in the side pathway of glycolysis.
• 2,3 diphosphoglycerate is required for hemoglobin to bind and release oxygen (BOHR curve)

• İki ATP glikolizin yukarı kademelerinde fosforilasyon için kullanılmıştır. Glikolizde Net 2 ATP elde edilir.
• Glikolizde tam oksidasyon olmadığı için ATP kazancı da düşüktür. Glukozun tam oksidasyonu CO2 ve H2O’ ya dönüştüğü zaman gerçekleşir ve 38 ATP molekülü elde edilir.

Deficiency of Pyruvate Kinase Enzyme

• Enzyme deficiencies or defects of the glycolytic pathway cause structural and functional disorders of erythrocytes.
• Pyruvate kinase deficiency is a genetic disease in erythrocytes.
• It is an autosomal recessive disease and causes severe anemia. This condition is a familial inherited disease.
• Deficiencies of other enzymes in the glycolytic pathway, such as pyruvate kinase, may also occur.
• Triosephosphate isomerase, 2,3 diphosphoglyceromutase, phosphofructokinase, Hexokinase are among these enzymes.
• Deficiencies of these enzymes affect the lifespan of erythrocytes.
• The erythrocyte lifespan, which is normally 120 days, is reduced in the absence of such enzymes.
• The reason for this is that erythrocytes, which cannot meet the need for adequate ATP, cannot protect their structural integrity. Another important reason here is the difficulty of releasing oxygen to the tissues.

• The progression of glycolysis in erythrocytes is as follows.
• While 1,3 diphosphoglycerate (1,3 DPG) continues on its way as 3-phosphoglycerate (3-PG) in normal cells, a different situation occurs in erythrocytes.
• 1,3 DPG is converted to 2,3 Diphosphoglycerate (2,3 DPG) by the enzyme Diphosphoglucomutase.
• Then, 2,3 DPG is converted to 3 phosphoglycerate (3-PG) by losing a Pi again with Diphosphoglycerate phosphatase enzyme.
• And then the other steps continue and lactic acid is formed.

Bohr Effect

• The Bohr effect is the oxygen binding curve of hemoglobin under a certain pressure.
• The amount of CO2 in the cell environment, pH, some glycolytic enzymes, 2,3DPG are important in the formation of this curve.
• The figure shows the normal position of the curve. A formation above or below this creates difficulty in transporting oxygen and leaving it to the tissues.
• Therefore, the curve showing the Bohr effect has physiological significance.
• When arterial blood enters the tissues, CO enters the erythrocytes by diffusion.
• Meanwhile, the pH drops and the affinity of hemoglobin for oxygen decreases. As a result, oxygen is released into the cell environment. H + HbO 2 O 2 + HHB

• Reactions in the lungs take place in contrast to those in the tissues. Here, the pH rises with the loss of CO2. In this case, the affinity of Hb for oxygen increases and the binding of oxygen to hemoglobin increases at low pressure.
• CO2 binds to hemoglobin, forming carbaminohemoglobin as seen below.

• Hb-Nh 2 + CO 2 Hb-NH-C-O

   + H + 

• O
• 2,3DPG binds to hemoglobin, which has a tetrameric structure, in a 1:1 ratio at neutral pH. This coupling results in the normal Bohr curve shown in the figure.
• As seen below, it becomes easier for hemoglobin to release oxygen.
• HO 2 + DPG HbDPG + O 2