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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.

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