Biochemistry Online: An Approach Based on Chemical LogicOne way of categorizing metabolic processes, whether at the cellularorgan or organism level, is as pathawy or as " catabolic ", which is the opposite and thus the separation of a macromolecule. Anabolism is powered by catabolism, where large molecules are anabolic pathway reductive down into smaller parts and then used ahabolic in cellular respiration. Many anabolic processes are powered by the hydrolysis of adenosine triphosphate ATP. Anabolic processes tend toward "building up" organs and tissues. These processes produce growth and differentiation of cells and increase in body size, a process that involves synthesis of complex ananolic Examples of anabolic processes include anabolic pathway reductive growth anabolic pathway reductive mineralization of bone and increases in muscle mass. Endocrinologists have traditionally classified hormones as anabolic or catabolic, depending on which testosterone propionate iran of metabolism they stimulate.
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At first glance, metabolism appears intimidating because of the sheer number of reactants and reactions. Nevertheless, there are unifying themes that make the comprehension of this complexity more manageable.
These unifying themes include common metabolites, reactions, and regulatory schemes that stem from a common evolutionary heritage. We have seen that phosphoryl transfer can be used to drive otherwise endergonic reactions, alter the energy of conformation of a protein, or serve as a signal to alter the activity of a protein.
The phosphoryl-group donor in all of these reactions is ATP. In other words, ATP is an activated carrier of phosphoryl groups because phosphoryl transfer from ATP is an exergonic process. The use of activated carriers is a recurring motif in biochemistry, and we will consider several such carriers here.
Activated carriers of electrons for fuel oxidation. In aerobic organisms, the ultimate electron acceptor in the oxidation of fuel molecules is O 2. However, electrons are not transferred directly to O 2.
Instead, fuel molecules transfer electrons to special carriers, which are either pyridine nucleotides or flavins. The reduced forms of these carriers then transfer their highpotential electrons to O 2.
Nicotinamide adenine dinucleotide is a major electron carrier in the oxidation of fuel molecules Figure The reduced form of this carrier is called NADH. Both electrons lost by the substrate are transferred to the nicotinamide ring. The other major electron carrier in the oxidation of fuel molecules is the coenzyme flavin adenine dinucleotide Figure FAD is the electron acceptor in reactions of the type.
The reactive part of FAD is its isoalloxazine ring, a derivative of the vitamin riboflavin Figure These carriers of high-potential electrons as well as flavin mononucleotide FMN , an electron carrier related to FAD, will be considered further in Chapter An activated carrier of electrons for reductive biosynthesis. High-potential electrons are required in most biosyntheses because the precursors are more oxidized than the products.
Hence, reducing power is needed in addition to ATP. For example, in the biosynthesis of fatty acids, the keto group of an added two-carbon unit is reduced to a methylene group in several steps. This sequence of reactions requires an input of four electrons. The extra phosphoryl group on NADPH is a tag that enables enzymes to distinguish between high-potential electrons to be used in anabolism and those to be used in catabolism.
An activated carrier of two-carbon fragments. Coenzyme A , another central molecule in metabolism, is a carrier of acyl groups Figure Acyl groups are important constituents both in catabolism, as in the oxidation of fatty acids, and in anabolism, as in the synthesis of membrane lipids. The terminal sulfhydryl group in CoA is the reactive site.
Acyl groups are linked to CoA by thioester bonds. The resulting derivative is called an acyl CoA. An acyl group often linked to CoA is the acetyl unit; this derivative is called acetyl CoA. Consequently, acetyl CoA has a high acetyl potential acetyl group-transfer potential because transfer of the acetyl group is exergonic. The use of activated carriers illustrates two key aspects of metabolism. Likewise, ATP and acetyl CoA are hydrolyzed slowly in times of many hours or even days in the absence of a catalyst.
These molecules are kinetically quite stable in the face of a large thermodynamic driving force for reaction with O 2 in regard to the electron carriers and H 2 O in regard to ATP and acetyl CoA. The 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 power. Second, most interchanges of activated groups in metabolism are accomplished by a rather small set of carriers Table The existence of a recurring set of activated carriers in all organisms is one of the unifying motifs of biochemistry.
Furthermore, it illustrates the modular design of metabolism. A small set of molecules carries out a very wide range of tasks. Metabolism is readily comprehended because of the economy and elegance of its underlying design.
Just as there is an economy of design in the use of activated carriers, so is there an economy of design in biochemical reactions. The thousands of metabolic reactions, bewildering at first in their variety, can be subdivided into just six types Table Specific reactions of each type appear repeatedly, further reducing the number of reactions necessary for the student to learn.
Oxidation-reduction reactions are essential components of many pathways. Useful energy is often derived from the oxidation of carbon compounds. Consider the following two reactions: These two oxidation-reduction reactions are components of the citric acid cycle Chapter 17 , which completely oxidizes the activated two-carbon fragment of acetyl CoA to two molecules of CO 2. Ligation reactions form bonds by using free energy from ATP cleavage.
Reaction 3 illustrates the ATP-dependent formation of a carbon-carbon bond, necessary to combine smaller molecules to form larger ones. Oxaloacetate is formed from pyruvate and CO 2. The oxaloacetate can be used in the citric acid cycle or converted into amino acids such as aspartic acid. Isomerization reactions rearrange particular atoms within the molecule. Their role is often to prepare a molecule for subsequent reactions such as the oxidation-reduction reactions described in point 1.
Reaction 4 is, again, a component of the citric acid cycle. This isomerization prepares the molecule for subsequent oxidation and decarboxylation by moving the hydroxyl group of citrate from a tertiary to a secondary position. Group - transfer reactions play a variety of roles. Reaction 5 is representative of such a reaction. A phosphoryl group is transferred from the activated phosphoryl-group carrier, ATP , to glucose. This reaction traps glucose in the cell so that further catabolism can take place.
We saw earlier that group-transfer reactions are used to synthesize ATP We will also see examples of their use in signaling pathways Chapter Hydrolytic reactions cleave bonds by the addition of water.
Hydrolysis is a common means employed to break down large molecules, either to facilitate further metabolism or to reutilize some of the components for biosynthetic purposes. Proteins are digested by hydrolytic cleavage Chapters 9 and Reaction 6 illustrates the hydrolysis of a peptide to yield two smaller peptides.
The addition of functional groups to double bonds or the removal of groups to form double bonds constitutes the final class of reactions. The enzymes that catalyze these types of reaction are classified as lyases Section 8. An important example, illustrated in reaction 7, is the conversion of the six-carbon molecule fructose 1,6-bisphosphate F-1, 6-BP into 2 three-carbon fragments: This reaction is a key step in glycolysis, a key pathway for extracting energy from glucose Section Dehydrations to form double bonds, such as the formation of phosphoenolpyruvate Table The dehydration sets up the next step in the pathway, a group-transfer reaction that uses the that uses the high phosphoryl transfer potential of the product PEP to form ATP from ADP.
These six fundamental reaction types are the basis of metabolism. Remember that all six types can proceed in either direction, depending on the standard free energy for the specific reaction and the concentration of the reactants and products inside the cell.
As an example of how simple themes are reiterated, consider the reactions shown in Figure The same sequence of reactions is employed in the citric acid cycle, fatty acid degradation, the degradation of the amino acid lysine, and in reverse the biosynthesis of fatty acids.
An effective way to learn is to look for commonalties in the diverse metabolic pathways that we will be studying. There is a chemical logic that, when exposed, renders the complexity of the chemistry of living systems more manageable and reveals its elegance. Some metabolic pathways have similar sequences of reactions in common—in this case, an oxidation, the addition of a functional group from a water molecule to a double bond, and another oxidation. ACP designates acyl carrier more It is evident that the complex network of reactions constituting intermediary metabolism must be rigorously regulated.
At the same time, metabolic control must be flexible, because the external environments of cells are not constant. Metabolism is regulated by controlling 1 the amounts of enzymes , 2 their catalytic activities , and 3 the accessibility of substrates.
The amount of a particular enzyme depends on both its rate of synthesis and its rate of degradation. The level of most enzymes is adjusted primarily by changing the rate of transcription of the genes encoding them. The catalytic activity of enzymes is controlled in several ways. Reversible allosteric control is especially important. For example, the first reaction in many biosynthetic pathways is allosterically inhibited by the ultimate product of the pathway.
The inhibition of aspartate transcarbamoylase by cytidine triphosphate Section This type of control can be almost instantaneous. Another recurring mechanism is reversible covalent modification. For example, glycogen phosphorylase, the enzyme catalyzing the breakdown of glycogen, a storage form of sugar, is activated by phosphorylation of a particular serine residue when glucose is scarce Section Hormones coordinate metabolic relations between different tissues, often by regulating the reversible modification of key enzymes.
Hormones such as epinephrine trigger signal transduction cascades that lead to highly amplified changes in metabolic patterns in target tissues such as the muscle Section The hormone insulin promotes the entry of glucose into many kinds of cells.
As will be discussed again in Chapter 15, many hormones act through intracellular messengers, such as cyclic AMP and calcium ion, that coordinate the activities of many target proteins.
Controlling the flux of substrates also regulates metabolism. The transfer of substrates from one compartment of a cell to another e.