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Friday, February 18, 2011

Metabolism of Fats and Proteins and Control of Metabolism and Metabolic Pool

Friday, February 18, 2011 - 5 Comments

Catabolism of glucose is most common metabolic pathway in cells. Animals are consumed fats and protein which may be used to harvest energy.

Metabolism of Fats:
Fats are built from long chain fatty acids and glycerols are triglycerides. Initial catabolism of fat begins with the digestion of triglycerides by way of an enzyme called lipase to glycerol and three fatty acid molecules.

Glycerol is phosphorylated and can enter glycolytic pathway at the level of glycerol dehydes 3 – phosphate free fatty acids move into mitochondrion where their carbons are removed, two at a time to form acetyl coenzyme A plus additional NADH and FADH2. Acetyl coenzyme A is then oxidized by Krebs’ cycle and NADH and FADH2 that are produced are oxidized via electron transport chain. One gram of fat provides about 2.5 times more ATP energy than does either 1g of carbohydrate of protein because the number of hydrogen atoms per unit weight of fat is greater than in carbohydrates of protein. This is why many animals store energy in the form of fat in adipose tissue.

Metabolism of Proteins:
Animals initially digest proteins to yield individual amino acids. Some of these are distributed throughout the body and used to synthesize new proteins. Other amino acids are transported in the blood or extra cellular fluid and comprise the amino acid pool. If needed for fuel these amino acids can be further degraded by removal of amino group to yield ammonia. This process is called deamination reaction.

 –  OH – COOH + H2O -------> R – C – COOH + NH2 + H2

In deamination, an oxygen atom replaces an amino group to form keto acid. Keto acid can then enter into kreb’s cycle. Finally the carbon skeleton of amino acid is dismantled and oxidized to CO2. Ammonia produced from complete catabolism of amino acid is highly toxic and must be excreted. On the average one gram of protein yields about same amount of energy that is 4 K. Cal as does 1g of glucose.

Control of Metabolism:
Cells are efficient and do not waste energy by making surplus substances they do not need or require in lesser amount. If certain amino acid is over abundant in amino acid pool, the anaerobic pathway that synthesizes that amino acid from an intermediate in kreb’s cycle is turned off. Most common mechanism for this control uses and product (feed back) inhibition. In end product inhibition, the end product of anaerobic pathway inhibits the enzyme that catalyzes key step in the pathway.
Controlling the catabolic activities ca control the activities of cell and the organism. Supposing if a muscle cell is working very hard and its ATP concentration begins to decrease, aerobic respiration increases. When ATP is sufficient to meet demand, aerobic respiration slows, sparing valuable organic molecules for other necessary functions. As with anabolism, control is based on regulating enzyme activity at strategic points in the catabolic pathway. As a result cells are thrifty, expedient and responsive in their metabolism.

Control of Glycolysis through Phosphofructokinase:
During glycolysis, fructose – 6 – phosphate is converted to fructose diphosphate by enzyme phosphofructokinase. It is sensitive to energy needs of cell and the ratio of ATP to ADP or AMP. It has receptor sites for specific inhibitors and activators.

Metabolic Pool:
Catabolic chemical reaction of glycolysis and Krebs cycle not only provide ATP but also make available metabolic pool of material that can be consumed for the synthesis or anabolism reactions of many important cellular components. The balance between catabolism and anabolism maintains homeostasis in the cell as well as the whole animal. The chemical reaction that takes place in the body may be divided into two categories on the basis components can gain lateral entry or not in main system.

(1)        Open system: The system of metabolic reaction in which a number of reactants from different sources can enter and participate in the system can be further processed is known as open system. Open system has two way flow of material into and out of it. Various compounds enter the pathways at different points so that carbohydrates, fats and proteins can all be oxidized. At the same time some of the intermediates of these pathways can be withdrawn from the energy harvesting machinery and used in synthesis reactions. Glycolysis and Krebs cycle are examples of open system and the products of glycolysis and Krebs cycle are all part of metabolic pool whereby material is added withdrawn.
(2)        Closed system: In some of the systems the chemical reactions take place completely in the closed environment and no reactant or substance can enter into the system till the final metabolic product is obtained, such a system is known as closed system.

Kreb’s Cycle (OR) Citric Acid Cycle (OR) Tri-Carboxylic Acid Cycle (TCA)

During metabolism the synthesis and breakdown of different organic compounds takes place through various pathways like the breakdown and synthesis of proteins, carbohydrates, fats and nucleic acids. These different pathways and intermediates are also responsible for the production of energy.
Kreb’s cycle, named after Hans Krebs who began working out its details in 1930s, is a series of reactions in which the pyruvate from glycolysis is oxidized to Co2 under aerobic conditions. Kreb cycle is also known as citric acid cycle or Tri-carboxylic acid cycle (TCA).

Steps involved in the process of Kreb cycle are:
(1)        Fate of pyruvic acid:
Pyruvic acid can form different compounds by different pathways i.e. it can be converted into lactic acid. It can be converted into acetyl coenzyme A us a result of oxidation.
(2)        Fate of Acetyl CoA:
It can either undergo condensation with itself or its derivatives to form fatty acids having 14 – 20 carbons. Acetyl CoA can also go through a series of reactions in Krebs cycle.
(3)        Formation of citrate:
Acetyl CoA enzyme condenses with oxaloacetate by an enzyme citrate synthatase to form citrate with the release of acetyl CoA. If the amount of oxaloacetate is very small then small number of acetyl CoA would be reacting with oxaloacetate leaving surplus acetyl CoA to go through another pathway for the formation of long chain fatty acids.
(4)        Formation of C is – acotinate and iso-citrate:
Citrate is changed first into C is – acotinate and then to iso-citrate under the enzyme acotinase. Equilibrium is established between citrate, C is aconitate and iso-citrate. It has been observed that most of the time this equilibrium is shifted towards the iso-citrate. If the concentration of iso-citrate in increased the formation of citrate will result which also indicates that the equilibrium also shift in the reserve direction.
(5)        Formation of oxalosucinate:
Iso-citrate is acted upon by an enzyme iso-citrate dehydrogenase using nicotinamide adenine dinucleotide (NAD) as coenzyme. As a result iso-citrate is converted into oxalosucciate and NAD is reduced to NADH2. Similar reaction is carried out by same enzyme using nicotindmide adenine dinucleotide phosphate (NADP) as coenzyme which is reduced to NDAPH2.
(6)        Formation of α-Ketoglutarate:
Oxalosucciante is changed into α-ketoglutrate by iso-citrate dehydrogenase with the help of coenzyme NAD or NADP. In this reaction carbon dioxide and NADH2 or NADPH2 are also released.
(7)        Formation of succinyl CoA:
α-ketoglutarate combines with acetyl CoA in the presence of coenzyme NAD and enzyme α-keoglutarate dehyrogenase to form succinyl coenzyme a carbon dioxide and NADH2.
(8)        Formation of Succinate:
Later on coenzyme a is removed from succinyl coenzyme A in the presence of guanosine diphosphate (GDP) and inorganic phosphate to form succinate and guanosine triphosphate (GTP). This reaction is carried out by an enzyme called succinyl CoA synthatase.
(9)        Formation of Funarate:
An enzyme succinic dehydrogenase removes hydrogen from succinate to form funarate.
(10)      Formation of Malate:
Fumarate reacts with water in the presence of enzyme fumarase to form malate.
(11)      Regenration of oxaloacetate:
Malate is oxidized by malic dehydrogenase and NAD forming oxaloacetate and NADH2. Thus oxalo acetate is again available to start another cycle.

Importance of CTA Cycle:
(1) Source of energy: In addition to routine organic compounds described above, by products like nicotinanide adenine dinucleotide (NADH2) and guanosine triphosphate (GTP) are the source of biological energy. NADH2 after oxidation produce energy whereas GTP is itself high energy phosphate compound.
(2) Oxidation of organic compounds taken as food: Oxidation of fats, carbohydrates and proteins take place through it or in other words it can be said that oxidation of all compounds having carbon atoms can take place through TCA cycle. Some of amino acids like alanine, glutamic acid and aspartic acid at one stage or the other enters into TCA cycle e.g. glutamic acid enters cycle after its transformation into α-ketoglutarate. Similarly alanine enters the cycle after its conversion into pyruvate.
(3) Intermediate compounds: TCA cycle is also involved in synthesis of intermediate compounds leading to the formation of larger molecules.

Verification of Krebs Cycle:
It was done by radioactive traces like C14 as radioactive carbon dioxide of different levels and reactions. After addition of radioactive carbon dioxide different chemical compounds produced like glucose, fats, amino acids were isolated and looked for radioactive carbon. In this way whole of metabolic reaction were verified including individual reactions, alternative metabolic pathways, intermediates of fats, carbohydrates and amino acids etc in the body cells as well as in test tubes.

Sunday, February 6, 2011

Fermentation and Aerobic Respiration

Sunday, February 6, 2011 - 0 Comments

Fermentation is either an evolutionary bypass that some organisms use to keep glycolysis functioning under anaerobic conditions or is a biological remnant that involved very easily in the history of life, when the earth’s atmosphere contained little or no oxygen. As with glycolysis, the presence of fermentation is strong evidence for common descent of organisms from primitive cells in which glycolysis and fermentation first appeared and still persists.

In fermentation hydrogen atoms that glycolysis generates are donated to organic molecules and then reduced compound can be an organic acid like lactic acid, acetic acid, propionic acid or an alcohol in the form of ethanol, butanol. Fermentation regenerates NAD, which is needed to drive glycolysis to ultimately obtain ATP. During fermentation glucose is not completely degraded, so considerable unusable energy still remains in the products. Beyond two ATP molecules formed during glycolysis, no more ATP is produced. Fermentation serves only to regenerate NAD (oxidized from of NADH).

Types of Fermentation:

There are two types of fermentation depending upon the end product obtained. The fermentation in which the end product is an alcohol is known as alcoholic fermentation where as the fermentation in which some acid specially lactic acid is formed is known as Lactic acid fermentation.
Alcoholic fermentation: The pathway from private to ethanol is called alcoholic fermentation and is catalysed by specific microbial enzymes.
Lactic acid fermentation: The pathway in which lactate or lactic acid is produced as end product from private is known as lactic acid fermentation.
There are certain animals cells that are deprived of oxygen, temporarily carry out lactic acid fermentation.

Types of Fermenting Organisms:
Two types of organisms can carry out fermentation, obligative or obligate anaerobic and Facultative anaerobic.
Obligative anaerobic organism:
The organisms that survive only in complete absence of molecular oxygen are termed as obligative or obligate anaerobic organisms. These include certain types of bacteria.
Facultative anaerobic organisms: The organisms that survive only in the absence of molecular oxygen are termed as facultative anaerobic organisms. They are certain bacteria, yeasts, animal muscle cells which can ferment nutrients when oxygen is absent to generate some ATP by providing NAD for glycolysis. Such organisms and tissues carry out more efficient energy harvesting when oxygen is present.
Aerobic respiration: The major source of ATP:
Anaerobic generation of ATP through glycolysis and fermentation is inefficient. The end product of glycolysis (pyruvate) still contains great deal of potential bond energy that can be harvested by further oxidation. Evolution of aerobic respiration in micro-organisms and in the mitochondria of eukaryotic cells became possible only after free oxygen had accumulated in the earth’s atmosphere as a result of photosynthesis. Addition of oxygen requiring stage to energy harvesting mechanisms provided cells with more powerful and efficient way f extracting energy from nutrient molecules. Indeed without mitochondria’s large scale ATP production life would have to be at a “snail’s space” and most animals present on earth today would never have evolved.
In aerobic respiration pyruvate that glycolysis produces is shunted into a metabolic pathway called Kreb’s cycle or citric acid cycle; NADH goes to electron transport chain. During this aerobic metabolism free oxygen accepts electrons and reduces to water together with production of 34 molecules of ATP from each molecule of pyruvate consumed.
Aerobic respiration is organized into Kreb’s cycle and electron transport chain. Two electron carriers’ mitotinamide adenine di-nucleotide (NAD) and falvin adenine di-nucleotide (FAD) act as hydrogen acceptors and reduce to NADH and FADH2.
Most of the remaining energy is in the form of NADH and FADH2. These two molecules are shuttled into electron transport chain. In this chain reduced NADH and FADH2 are oxidized and their electrons are passed along a series of oxidation reduction reaction to the final acceptor oxygen. During this phase of the cycle, three molecules of Co2 are generated from each pyruvate molecule and some energy is harvested in the form of ATP.

Process of Glycolysis, the Process of Metabolism and its Evolutionary Perspectives

It is the initial sequence of catabolic chemical reactions in which six carbon glucose molecules is broken down into two molecules of three carbon compound called pyruvate of pyruvic acid with net production of two molecules of ATP when glucose is completely burned in a test tube it will give about 690,000 calories of energy per mole in the form of heat. In the cell some of this energy is not lost as heat but is retained in the form of ATP.
Steps involved in the process of glycolysis:
(1)        Glucose is converted to glucose – 6 – phosphate with the help of an enzyme hexokinase in the presence of ATP.
(2)        Glucose – 6 – phosphate is rearranged to form its isomes fructose – 6 – phosphate with the help of an enzyme phosphogluco isomerase.
(3)        Fructose – 6 – phosphate reacts with another molecule of ATP to form fructose – 1, 6 – diphosphate or hexose diphosphate with the help of an enzyme phosphor fructokinase.
(4)        Fructose – 1, 6 diphosphate is then either converted into 3 – phosphoglyceral dehyde by dihydroxy acetone phosphate under the enzyme aldolase. There is established equilibrium between these compound by inter converting into one another through an enzyme isomerase – 3 – phosphoglyceral dehyde is utilized at a faster rate and when there is deficiency of this compound, then dihydroxy acetone phosphate is converted into 3 – phosphoglyceral dehyde which is processed further by glycolysis.
(5)        3 – phosphoglyceral dehyde is initially oxidized by NAD and then the inorganic phosphate present in the cytoplasm combines to form 1, 3 – phosphoglyceric acid in the presence of enzyme triose phosphate dehydrogenase.
(6)        1, 3 – phosphoglyceric acid is then converted to 3 – phosphoglyceric acid or 3 – phosphoglycerate along with the release two ATP molecules by the enzyme phosphoglycerokinase.
(7)        3 – phosphoglyceric acid or 3 – phosphoglycerate is then converted into 2 – phosphoglyceric acid or 2 – phosphoglycerate in the presence of phosphoglyceromutase.
(8)        2 – phosphoglyceric acid or 2 – phosphoglyceratase is converted into phosphoenol pyruvic acid or phosphoenopyruvate in the presence of enolase.
(9)        Finally phosphoenol pyruvic acid or phosphoenylpyruvate is converted into pyruvic acid or pyruvate along with the production of two more ATP molecules by the enzyme pyruvate kinase.
Energy yielding steps are:
(1)        During process of glycosis two ATP molecules were used as starter energy to convert Glycosets fructose 1 – 6 biphosphate.
(2)        Two ATP molecules are formed during the conversion of 1, 3 – diphosphoglycerate to 3 – phosphoglycerate.
(3)        Two additional ATP molecules are released when phosphenolpurate is converted into pyrute the end – product of glycolysis.
(4)        In addition to four ATP molecules produced during glycolysis, energy rich compounds NADH2 is also produced which is used to make the ATP by oxidative phosphorylation.
End result of Glycolysis: All the reactions of glycolysis are performed by soluble enzymes that are present in the cytosol and are not found in mitochondrion. Two moles of ATP are needed to start of glycolysis of glucose and during the oxidative reaction of glycolysis these two moles of ATP are regained. The NADH2 formed in above reactions is oxidized via the electron transport chain to form three more ATP molecules. The end result of glycolysis is the formation of two moles of pyruvic acid from each mole of glucose together with two moles of ATP. Although glycolysis does not efficiently harvest all the available energy from glucose, it was the only way most organisms could harvest energy and generate ATP molecules for hundreds of millions of years during the anaerobic stages of early life on earth.
Evolutionary Perspectives on Glycolysis:
All forms of animal life including man carry on glycolysis within their cells, a metabolic memory of animals’ evolutionary past – if glycolysis is such an inefficient method of harvesting energy, why has it persisted?
One reason might be that evolution is slow, incremental process involving change based on past events when glycolysis first evolved the cells possessing it had competitive advantage over these that did not.
Importance of Glycolysis as observed through biochemistry:
Biochemistry of contemporary organisms indicates that only those organisms capable of glycolysis survived the early competition of life on earth. Later on the evolutionary changes in catabolism build on this success. During this building process, glycolysis was not discarded but used as a stepping stone for the evolution of another process for complete breakdown of glucose.

How cells convert Energy? (OR) How ATP is obtained? (OR) Describe Phosphorylation and Chemiosmossis

Within their cells, animals make ATP to carry out normal activities of the body. The process of formation of ATP is known as phosphorylation. There are number of processes through which ATP can be obtained. Two of these processes are common namely substrate level phosphorylation and chemiosmossis.

(1)        Substrate level phosphorylation:
The generation of ATP by coupling strongly exergonic reaction with ATP synthesis from ADP and phosphate is called substrate level phosphorylation. It appeared very early in the history of organisms because organisms initial use of carbohydrates as an energy source is accomplished by substrate level phosphorylation. The mechanism for substrate level phosphorylation is present in most living animal cells. Substrate level phosphorylation is one of the most fundamental of all ATP generating reactions. ATP formation from ADP and phosphate requires the input of energy of 7.3 K. Cal:

(2)        Chemiosmosis:
There is still other method of generating ATP that is more efficient and effective and is called chemiosmosis and it takes place in the mitochondrion. In the mitochondrion trans membrane channels are present in the mitochondrial membranes that can pump protons. These proton pumps use flow of electrons to induce a shape change in the protein, which in turn, causes protons to move out of the inner compartment of a mitochondrion. As the proton (H+) concentration in the outer compartment of mitochondrion becomes greater than that of the inside compartment, other protons are driven across the membrane by electrical – chemical proton gradient. As protons move down this gradient between outer and inner mitochondrial compartments, they induce the formation of ATP from ADP, phosphate, and the enzyme ATP synthetase.
The electrons that derive the electron transport system involved in chemiosmosis are obtained form chemical bonds of food molecules in all organisms and from photosynthesis in plants. This electron stripping process is called cellular respiration or aerobic respiration because free oxygen is needed. Basically aerobic respiration is the oxidation of food molecules to obtain energy.

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