Structural Biochemistry/Metabolism Coupled Reactions

= Metabolic Pathways = The living systems are highly ordered and utilize energy. This energy is not created by the living system. It is instead, obtain from the environment, and then processed into usable forms. Metabolism is a series of chemical reactions beginning with a particular molecule and converting it into another molecule or molecules. It has many defined pathways in the cells which are interdependent and their activity is coordinated very sensitively by means of communication in which allosteric enzymes are predominant.

The overview of the process is that through photosynthesis, carbon dioxide and water, with the help of light, is converted into organic molecules, or food in our sense. Through cellular respiration, the organic molecules are converted back into carbon dioxide and water. Metabolism is the total chemical reaction occuring in the body, and it involves molecular interaction. It is highly regulated and yields a change in energy content of the reactants. The metabolic pathways is a series of reaction controlled by multiple enzymes.

= Energy Transformation = Organisms transform energy, and energy is the capacity to do work. There are kinetic energies and potential energy. Kinetic energy is the energy of motion, it can be used to perform work. Examples of kinetic energy are light, heat, and electricity. Potential energy is stored energy. An example is electrochemical gradients. Light can be transformed into chemical bonds. Chemical bonds can be transformed to be used for mechanical work. Energy transformation must follow the two thermodynamic laws. The first law -conservation of energy - is that energy can neither be created or destroyed; it can only change forms. The Universe has a constant form of energy. The second law of that energy transformation yields an increase in the entropy of the universe. Entropy is a measure of disorder. But this is referring to the a closed system, one in which matter is isolated from the surrounding. So as long as the entropy of the system and surrounding increases, entropy of the system itself may decrease.

Catabolic Reactions
Catabolic Reactions are metabolic pathways in which reactions convert energy from fuels into biologically useful forms.

Anabolic Reactions
Anabolic Reactions are metabolic pathways in which reactions require energy to proceed.

Amphibolic Reactions
Amphibolic reactions are metabolic pathways that involves both catabolic and anabolic reactions.

Activated Carriers
ATP is an activated carrier of phosphoryl groups because phosphoryl transfer from ATP is an exergonic process. The use of activated carriers is a motif in biochemistry and most function as coenzymes:

1. Activated Carriers of Electrons for Fuel Oxidation. In aerobic organisms electrons are not transferred directly to O2 despite being the ultimate electron acceptor. Rather, fuel molecules transfer electrons to special carriers which are either pyridine nucleotides or flavens. The reduced form of these carriers then transfer their high-potential electrons to O2.

2. Activated Carrier of Electrons for Reductive Biosynthesis. High potential electrons are required in most biosyntheses because the precursors are more oxidized then the products. Hence, reducing power is needed in addition to ATP.

3. An Activated Carrier of Two-Carbon Fragments. Coenzyme A, another central molecule in metabolism is a carrier of acyl groups. Acyl groups are important constituents in both catabolism, and anabolism. The terminal sulfhydryl group of CoA is the reactive sites. Acyl groups are linked to CoA by thioester bonds resulting derivative called acyl CoA. The hydrolysis of thioester is thermodynamically favorable that that of an oxygen ester because the electrons of C=O cannot form resonance structures with C - bonds, making acetyl CoA have a high acetyl-group transfer potential because transfer of acyl group is exergonic. Acetyl CoA carries an activated acetyl group, just as ATP carries an activated phosphoryl group. Aceyl-CoA

Use of activated carriers illustrates that Kinetic stability of these molecules in the absence of specific catalysts is essential for their biological function because it enables enzymes to control the flow of free energy and reducing powers. Secondly most intercharges of activated groups in metabolisms are accomplished by rather small set of carriers such as ATP, NADH and NADPH.

Vitamins
Almost all activated carriers that act as coenzymes are derived from vitamins. Vitamins are organic molecules that are needed in small amounts in the diets of some animals. They play the same roles in nearly all forms of life, but higher animals have lost the capacity to synthesize the in the course of evolutions.

Vitamin B6,coenzyme pyridoxal phosphate. Typical reaction type is group transfer to or from amino acids. Deficiency can lead to depression, confusion and convulsion.

Reiteration in Metabolism
Six fundamental reaction types that are the basis of metabolism:

1. Oxidation-reduction reactions are essential components of pathways. Useful energy is derived from the oxidation of carbon compounds.

2. Ligation reactions form bonds by using free energy from ATP cleavage

3. Isomerization reactions rearrange particular atoms within a molecule.

4. Group-transfer reactions play a variety of roles.

5. Hydrolytic reactions cleave bonds by the addition of water.

6. Functional groups may be added to double bonds to form single bonds or removed from single bonds to form double bonds.

Regulation in Metabolism
Metabolic reactions must be to rigorously related but at the same time must be flexible to adjust metabolic activity to constantly changing external environment cells. Metabolism are regulated through:

1. Controlling the Amounts of Enzyme. Amount of particular enzyme depends on both its rate of synthesis and its rate of degradation.

2. Controlling Catalytic Activity. Catalytic activity of enzymes are controlled in several ways: (a.) reversible allosteric control (b.) feedback inhbition (c.) reversible covalent modification (d.) hormones coordinate metabolic relations between different tissues (e.) energy status of cell --> energy charge

3. Controlling the Accessibility of Substrate. Compartmentalization segregates opposed reactions and Controlling the flux of substrates.

Metabolism from RNA World
The current thinking is that RNA was an early biomolecule that in an early RNA world would have served as a catalyst and information-storage. Activated carries such as ATP, NADH, FADH2 and coenzyme A contain adenosine diphosphate units evolved from early RNA catalyst. Non-RNA units such as isoalloxazine ring may have been recruited to serve as efficient carriers of activated electrons and chemical units, which were functions not performed by RNA itself. Then when a more versatile proteins replaced RNA as the major catalysts, the ribonucleotide coenzymes stayed essentially unchanged because they were already well suited to their metabolic roles. With the advent of protein enzymes, these important cofactors evolved as free molecules without losing adenosine diphosphate vestiage of their RNA-world ancestry explaining why molecules and motifs of metabolism are common to all forms of life.

=Thermodynamics of Pathways= Thermodynamically unfavorable reactions can be driven by a thermodynamically unfavorable reaction when it is coupled. This is because a pathway must satisfy two criteria: (1.) the individual reactions must be specific and (2.) the entire set of reactions that constitute the pathway must be thermodynamically favored. A reaction that is specific will yield only one particular product or set of products from its reactants due to enzyme specificity. Thermodynamics of metabolism is most readily approached in relation to free energy, which states that a reaction can occur spontaneously only if $$\Delta G$$ is negative. This is due to the formation of products C and D from subtrates A and B given by the formula
 * $$\Delta G = \Delta G^\circ + R T \ln Q [C][D]/[A][B] \,$$

Thus $$\Delta G$$ depends on the nature of the reactants and their concentrations, which leads to thermodynamically fact that overall free-energy change for a chemically coupled series of reactions is equal to the free-energy changes of the individual steps.

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