Metabolism is the set of chemical transformations that take place in living organisms
The highly coordinated cellular activity allows you to:
- obtain chemical energy from the environment (sunlight or degradation of nutrients)
- converting nutrient molecules into monomeric molecules, characteristic of the cell itself
- synthesize polymers (proteins, nucleic acids, lipids, polysaccharides) from monomeric precursors
- Synthesize and degrade the cell's typical biomolecules (lipid membranes, cell messengers, etc.)
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It is an ordered sequence of reactions catalyzed by enzymes.
In a metabolic pathway, a precursor molecule is converted into a product through a series of intermediates (metabolites).
CATABOLISM → degrading phase of metabolism: molecules derived from nutrients are converted into simpler final products, energy is released.
ANABOLISM → phase of biosynthesis of the metabolism: the simplest precursors are converted into biological molecules; it requires energy.
The metabolic pathways can be linear or nonlinear (convergent, divergent, or cyclic).
- In the metabolic pathways converging from different precursors, a single final product is generated
- In the ways diverging from a single precursor, there are different end products
- In the cyclic pathways, one of the starting molecules is regenerated, another is converted into the final product
The catabolic pathways oxidize nutrient molecules and produce free energy in the form of:
1. Adenosine triphosphate ( ATP )
2. Electron conveyors in reduced form ( NADH, NADPH, FADH 2 )
4. The anabolic pathways use energy for the synthesis of biological molecules: This occurs due to the transfer potential of the phosphoric group of ATP and the reducing power of NADH, NADPH, and FADH 2.
The control of the metabolic pathways takes place through the coordinated modulation of catabolism and anabolism. The main mechanism consists of the separate regulation of the sequences of catabolic and anabolic reactions (if one way works, the other is blocked and vice versa). In the catabolic and anabolic pathways which share the same starting compounds or end products, at least one stage is catalyzed by different enzymes, which are therefore subject to separate regulation. The anabolic and catabolic pathways that connect the same compounds have different intracellular locations.
The substrate concentration influences the initial velocity (V 0) of an enzymatic reaction, according to the Michaelis-Menten equation.
Often the physiological concentration of the substrate is close to the Km values, so small variations of [S] involve considerable variations in the speed of reaction (first-order reaction).
The enzymes of a certain metabolic pathway work in sequence and most follow the Michaelis-Menten model described.
One or more enzymes (regulatory enzymes) can increase or decrease their catalytic activity in response to certain stimuli. In many metabolic pathways, the first enzyme in the sequence is a regulatory enzyme.
There are two classes of regulatory enzymes:
1. Enzymes regulated by reversible covalent modifications
2. Allosteric enzymes: they bind to molecules, called allosteric modulators or effectors, with the non-covalent and reversible bond.
Allosteric modulators can be inhibitors or activators.
The regulatory enzymes typically are positive, whose substrates also behave as modulators (homotropic).
Regulatory enzymes whose substrates do not act as modulators are called heterotopic (they can be positive or negative).
Allosteric regulatory enzymes contain two or more subunits.
Besides the catalytic sites (C), one or more regulatory or allosteric sites are present, generally on different subunits (R) for the binding of the modulators (inhibitors or activators).
Allosteric enzymes undergo conformational changes induced by the binding of the modulator VARIATION of the enzymatic activity.
Allosteric regulatory enzymes have kinetic properties that differ from the Michaelis-Menten model described.
In the case of a homotropic enzyme, in which the substrate also acts as a positive modulator, the curve is of the sigmoid type (Km is replaced by K 0.5).
The kinetics of heterotropic regulatory enzymes (modulator other than the substrate) is modified by the presence of activator or inhibitor
(a) The sigmoid curve in the presence of an activator becomes more similar to a hyperbolic curve, while in the presence of an inhibitor it becomes more sigmoid in this kinetics it does not change V max but K 0.5.
(b) For other regulatory enzymes, there is kinetics in which only the V max varies.
The sigmoid curve is caused by the cooperative bonding of the substrate.
Remember that the binding of O 2 to the heme of Hb subunit (which is not an enzyme) facilitates the binding of other O 2 molecules to the heme groups of the other subunits → POSITIVE COOPERATIVE EFFECT.
Sigmoid kinetics can be explained on the basis of two models:
(a) Concerted model - Monod model, Wyman, and Changeux.
The enzyme exists in two conformational states:
- Thelow affinity and high affinity are in balance with each other. The ligand binds the O state more easily, removes the shape from equilibrium, and this increases the affinity for the substrate
(b) Sequential model - Koshland model:
The various subunits can take on different conformations:
- low affinity or high-affinity O
The bond with the substrate induces conformational modifications that facilitate the passage of the other subunits from to O.
This model explains both positive and negative cooperativity.
In some metabolic pathways, an intermediate, often the end product, functions as an allosteric inhibitor of the first enzyme that regulates the pathway.
In this way, the downstream enzymes work at a reduced speed due to a lack of substrate, the quantity of the final product adapts to the needs of the cell.
The bacterial multi-enzyme system that converts L-threonine to L-leucine is an example.
The regulation of branched metabolic pathways is based on:
1. presence of isoenzymatic forms (enzymatic multiplicity) if the products of the same route are required for other routes
2. sequential feedback
3. cumulative feedback
4. multivalent feedback
5. synergic feedback
The activity of many enzymes is regulated through reversible covalent modifications on one or more amino acid residues.
The modification reactions are decisive for the enzymatic function; they regulate its affinity for the substrate (increase or decrease).
These changes are inserted or removed by other enzymes.
Among the numerous modification reactions (> of 500), the most common are: phosphorylation, acetylation, adenylation, myristoylation, ubiquitination, ADP-ribosylation, methylation. The most important type of covalent regulation is phosphorylation/dephosphorylation.