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Home Masters dr Krzysztof Michalak Wykłady z biochemii Trzeci Wykład Wprowadzający - Spalanie i synteza tłuszczów, Los glicerolu, Synteza kwasów tłuszczowych

Trzeci Wykład Wprowadzający - Spalanie i synteza tłuszczów, Los glicerolu, Synteza kwasów tłuszczowych


Lecture 3

Combustion and synthesis of fats.

Welcome to the next lecture in the series "Biochemistry in a nutshell." Today will discuss the fat burning metabolic pathways and their synthesis. Burning fat is primarily occurring in the mitochondria b-oxidation of fatty acids. As for the synthesis of this will be discussed trends in the cytoplasm of the synthesis of fatty acids. At first let's take the fire for combustion processes, since it is a natural continuation of the previous lecture on combustion of carbohydrates.

Triglyceride - a basic chemical compound which is a fatty fuel. It can circulate in the blood itself. May be incorporated into plasma lipid fractions such as VLDL, LDL, HDL, chylomicrons, in which it is transported between the different tissues of the body. It can finally be put aside as a reserve in fat cells. The first stage of combustion occurs in the triglyceride molecule most surprisingly in adipose tissue. This applies to both circulating triglycerides in the blood and those released from adipose tissue. It depends on the distribution of particles in the glycerol and 3 fatty acids. Fatty acids enter the blood, where they are collected by the tissue to burn.

The fate of glycerol depends on the presence in a given tissue glycerol kinase enzyme that attaches a phosphate group to it. If the tissue has the enzyme, glycerol is converted to gliceraldehydo-3P, an intermediate of glycolysis and pentose cycle. Occurs in a fire or use for synthesis. If the tissue does not have this enzyme, glycerol is thrown into the blood. It circulates there until reaches the tissue that the enzyme possesses. Enzyme is not in the adipose tissue. It is very important news for all those who are overweight. This means that the glycerol formed from triglyceride breakdown can not be used to rebuild a new triglyceride molecule. This will detail exactly arcyważny discussed in the near future, because the processes taking place in this cell are somewhat more complex.

Assuming that the glycerol molecule have been completely burned, a summary of all the intermediate reactions (conversion of pyruvate, acetyl-CoA and burned in the Krebs cycle) will look like this:

C3H8O3 (glycerol) + 3 ½ O 2 + 22 P + 22 ADP ® 3 CO2 + 4 H2O + 22 ATP

In terms of play and - with 100 g of glycerol can be achieved 23.9 mol ATP.This value is comparable with glucose (21.1mola/100g).

Let us now analyze the fate of released fatty acids. However, in talking about biochemistry Free Tłuszowych acids (PUFA), is in fact they do not move independently in the blood, but are transported by proteins. In the blood they are transported by the basic plasma protein - albumin. Inside the cells, while it is a fatty acid binding protein, or protein Z. Isolated move only short fatty acids, which are more soluble in water. After entering the cell fatty acids are first activated to be able to enter into further reactions of combustion.Activation consists of binding to the carboxy end of the molecule known to us already coenzyme A. This reaction occurs at the expense of degradation of ATP to AMP and pyrophosphate, which requires two high-energy bonds.Can occur in both the cytoplasm and in mitochondria. This is called an active molecule, regardless of the length of carbon chain fatty acid - acyl-CoA.

Neither free fatty acid or acyl-CoA can not penetrate to the interior of the mitochondrion itself. In the process of transport through the membrane attend a special relationship of L-carnitine. I am writing this because there are a lot of reports on the important role of this compound in the combustion process not only fat but also glucose. There is strong evidence suggesting the possibility of developing a relative deficiency of this compound on a vegetarian diet. Such deficiency can hinder the transport of fatty acids into the mitochondria, promote the development of diabetes and lactic acidosis.L-carnitine is synthesized in the body from two amino acids lysine and methionine, and its synthesis is necessary vitamins PP, B6, C and iron. Both of these amino acids are essential in the diet, ie the body is unable to synthesize the sugar. Characterized by a high content of carnitine, primarily meat. In the case of a diet low in meat is limited to provide both of these amino acids, as well as carnitine itself.

But back to the burning of fatty acids. Activated fatty acid, or acyl-CoA is already in the mitochondrion. Here is the definitive burning. Generally, the combustion process can distinguish two stages. First - it is cut into fragments of the fatty acid dwuwęglowe, or acetyl-CoA molecules. Second - it's been previously discussed combustion of acetyl-CoA in the Krebs cycle.So we will only detail the first stage.

Cut into pieces dwuwęglowe involves disconnecting from the end of another carboxylate acetyl-CoA molecules. If the fatty acid has an odd number of carbon atoms, are special enzymes degrade the odd tip. However, given that the vast majority of fatty acids have an even number of carbon atoms, the process is quantitatively marginal. Let's examine the process of cleavage of one molecule of acetyl-CoA:

R-CH2-CH2-CO ~ CoA ® R-CH = CH-CO ~ CoA to move the two carbons on the FAD

R-CH = CH-CO ~ CoA ® R-CHOH-CH2-CO ~ CoA to connect the water molecules

R-CHOH-CH2-CO ~ CoA ® R-CO - CH 2-CO ~ CoA to move the two carbons on the NAD

R-CO - CH 2-CO ~ CoA ® R-CO ~ CoA + CH3-CO ~ CoA

disconnection of acetyl-CoA, free CoA to join the rest of the carbon chain R.

At one stage of removing acetyl-CoA thus obtain a FADH2 and 1 NADH2.Since the oxidation of FADH2 gives 2 molecules of ATP and NADH2 - 3 ATP, oxidation of hydrogen for a total of five ATP molecules.

Przeprowadźmy now calculate the energy balance of combustion 1 molecule of palmitic acid, the basic - 16-carbon fatty acid. Is made seven cuts, resulting in a 8 molecules of acetyl-CoA. Each cut delivers 5 ATP, and each acetyl-CoA in the Krebs cycle gives 12 ATP. Subtract the two molecules must be still used for the first reaction of fatty acid activation. The final balance sheet so it is 7 × 5 + 8 × 12 - 2 = 129 molecules of ATP. In terms of play, with 100 g of palmitic acid can be 50.4 mol ATP. This value is about 2.5x higher than for glucose.

In the case of unsaturated fatty acids, there are special mechanisms that allow you to bypass the double bond during the cutting of acetyl-CoA. To not go into excessive detail, suffice it to say that each double bond in the molecule of a fatty acid molecule of ATP is 3 less in the overall mix. Double bonds are not so significantly reduce the calories of fat, leads to the need for production of additional enzymes in the mitochondria by reducing the efficiency of his work as a whole. Additionally, and in fact is above all, the existing double bonds in the molecule very easily react with various free radicals arising in the cell, resulting in the formation of various toxic compounds. Removing these toxins binds to a cell with considerable effort, energy.

Synthesis of fatty acids

Synthesis of fatty acids is not a simple reversal of the combustion reaction, but a separate process for independent mechanisms of biochemical regulation.Combustion occurs in the mitochondrion, synthesis and takes place in the cytoplasm of the cell. As a result of combustion of fatty acids, hydrogen is transferred to the NAD and FAD. Synthesis, however, serves as a hydrogen donor NADPH2. In both cases, the carbon skeleton is used acetyl-CoA. Let us now slightly more detail how the synthesis of fatty acid.

Two basic compounds are used for the synthesis of acetyl-CoA and NADPH2.The source of acetyl-CoA can be either proteins, fats and carbohydrates. In order to use the synthesis must leave the mitochondria.However, it does not leave the mitochondria directly. There is first of its connection with oxaloacetate in the citrate and citrate only leaves the mitochondrion. The cytoplasm is the distribution of citrate back to acetyl-CoA and oxaloacetate. This reaction requires energy, however, here one molecule of ATP. Oxaloacetate is converted to malate and goes back to the mitochondrium.NADPH2 formed in the combustion cycle pentozowym glucose. Its source, in addition to sugar, can also be most amino acids.Extending the chain fragments followed dwuwęglowymi.Acetyl-CoA molecule is attachable to an existing chain, then the oxygen in the keto group is converted into hydrogen. Synthesis of fatty acid is so interesting that all the reactions indicated below with the exception of the number "2" - connecting the CO2 - are performed by one big molecule of enzyme, which consists of several subunits, each of which performs a single reaction. This "gluing" all the enzymes of one pathway results in very significant improvements in efficiency of the whole process, because particles do not have to look in the cytoplasm. The various intermediates are transferred from one subunit to the next just like a well organized assembly line. What's more, this tape is closed in a circle, ie the fatty acid elongation by two carbons reaches the same point in space, which took off [i].

Let's further elongation reactions of fatty acid molecules:

1st At the beginning of the first enzyme molecule attaches acetyl-CoA which is the seed of synthesized fatty acid.

CH3-CO ~ CoA + enzyme ® CH3-CO ~ enzyme + CoA

2nd All subsequent acetyl-CoA molecules are first activated by attaching molecules of CO2. The reaction does not require energy:

CH3-CO ~ CoA + CO2 ® COOH-CH2-CO ~ CoA (malonyl-CoA)

3rd Malonylowa Group is also attachable to the enzyme in the vicinity of the acetyl (acyl)

CH3-CO ~ enzyme + COOH-CH 2-CO ~ CoA ® CH3-CO ~ ~ CO enzyme-CH2-COOH + CoA

4th Acetyl group (acyl) is transferred to the malonylową, detaches from the back of CO2 molecule:

CH3-CO ~ ~ CO enzyme-CH2-COOH ® enzyme ~ CO-CH2-CO-CH3 + CO2

5th The first hydrogenation of the particle:

enzyme ~ CO-CH2-CO-CH3 + NADPH2 ® enzyme ~ CO-CH2-CHOH-CH3

6th Disconnection of water molecules:

enzyme ~ CO-CH2-CHOH-CH 3 ® enzyme ~ CO-CH = CH-CH3 + H2O

7th The second hydrogenation of the particle:

enzyme ~ CO-CH = CH-CH 3 + enzyme ~ NADPH2 ® CO-CH2-CH2-CH3 (acyl-enzyme)

8a. The transfer of acyl group "on the left." Continue from step 3 reaction

enzyme ~ CO-CH2-CH2-CH3 ® CH3-CH2-CH2-CO ~ enzyme

8b. If fatty acid is already long enough, followed his separation from the enzyme:

enzyme ~ CO-C n H 2n +1 + H 2 O ® C n H 2n +1- enzyme + COOH

Let us now compare briefly the synthesis and breakdown of fatty acids from an energy point of view. NADPH2 NADH2 and are themselves energetically almost equivalent. In mitochondria there is an enzyme that transfers hydrogen between these compounds without any energy input. Both therefore correspond to approximately the energy contained in the three molecules of ATP. Recall that the cycle of decay pentozowym glucose molecule produces 12 NADPH2, equivalent to 36-five molecules of ATP. The total burning of glucose gives the 38 ATP. As you can see these values are almost identical.During the cutting of a fatty acid to acetyl-CoA is formed and FADH2 NADH2 corresponding to 5 molecules of ATP. Embedded acetyl-CoA synthesis are needed during the two molecules NADPH2, which corresponds to 6 molecules of ATP. In addition to transport each molecule of acetyl-CoA outside the mitochondrion requires one molecule of ATP.Because of cuts or built-in case palnmitynianu 7, and acetyl-CoA molecules 8, the difference between synthesis and degradation of the fatty acid molecule is only 15 molecules of ATP. Given that obtained from burning up 129 ATP, this is only about 12% of its energy value [ii].

Now compare how much ATP still get a burning trail of glucose in glycolysis and the Krebs cycle, and how much, if we first synthesize palmitate from it, and then burn it.

For the synthesis of a palmitate molecule need 8 acetyl-CoA molecules and 14 molecules NADPH2. To obtain this amount, you need to spread the pathway of glycolysis and glucose and 4 molecules in the cycle pentozowym 7 / 6 molecule:

a) 4 C6H12O6 ® 8 CO 2 + 8 CH3-CO ~ CoA + 56 ATP (glycolysis)

b) C6H12O6 + 7 H20 ® 7 CO 2 + 14 NADPH2 (cycle pentozowy)

c) 8 CH 3-CO ~ CoA + 8 ® 8 citrate oxaloacetate (leaves the mitochondrion)

d) 8 + 8 ATP citrate ® 8 oxaloacetate (back to mitoch.) + 8 CH3-CO ~ CoA

e) 8 CH 3-CO ~ CoA + 14 NADPH2 ® C15H31COOH + 6 H2O + 8 CoA

To summarize the above reactions, and omitting water and CO2:

C6H12O6 ® C15H31COOH + 48 ATP

Burning palmitate, as we calculated earlier, it gives 129 molecules of ATP.So in total conversion of glucose to palmitate molecule, and then burning it, it gives 129 48 = 177 ATP molecules. If the burn glucose directly in the pathway of glycolysis and the Krebs cycle, we get x 38 = molecules of ATP.In addition, account must still be leveling two amendments: the first molecule of ATP is used for activation of glucose into the pentose cycle. The second is related to reaction No. 3 of glycolysis (lecture 2). For the direction of the setting in glycolysis consumes ATP (4x), while for the opposite direction occurs in a cycle pentozowym - no. Since in this reaction cycle occurs pentozowym here x will dominate the direction of glycolysis. In total, however, it becomes not 4x, but x-profit so it's a molecule of ATP.

To sum up: Route glucose palmitate ® combustion ® provides 177 - + = 177 ATP, whereas ATP can be burned directly. The difference of ATP molecules is so small that it can be treated as a masterpiece of evolution. Conversion of carbohydrates into fat, lets see how the store 90% of the energy contained in carbohydrates.
Case under consideration is of course a special case of metabolic, because acetyl-CoA can be derived not from sugar but from amino acids or fat. Then the sugar can be consumed in the burn cycle pentozowym. With the participation of the sugar molecule created when a molecule of palmitate.Converting to grams: 100g carbs 122g can give then palmitate.

To hear the next lecture on combustion of amino acids.

[And] Strictly speaking, we are dealing with a complex of two identical molecules of the enzyme in the shape of croissants, which comes into contact ends form a closed ring. After elongation by two carbons fatty acid is so on the other end of macromolecules, symmetrical relative to the starting point. Back to the same location in space while the extension takes about 4 carbons.

[Ii] The calculations are estimates. In fact NADPH2 NADH2 and do not match exactly.

Author: Krzysztof Piotr Michalak. All rights reserved.
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