Introduction to Metabolism

• Metabolism is a network of interconnected metabolic/biochemical reactions that occur within living cells in an organized, integrated, and regulated manner.
• Metabolism is related to various biomolecules, including carbohydrates, lipids, proteins, and nucleoproteins.
• Metabolism involves the interconversion of chemical compounds within the body.
• Metabolite precursors are transformed into end products through specific intermediates.
• Metabolism is the sum of chemical changes that convert nutrients into energy, complex cell substances into simpler forms, and simple substances into functional complex biomolecules.
• Normal metabolism is vital for health, growth, reproduction, and survival.
• Enzymes, along with coenzymes, biocatalyze specific metabolic reactions, making enzymes functional units of metabolism.
• Hormones are chemical messengers of the human body that regulate enzyme activity by either stimulating or inhibiting.
• Enzyme reactions are organized into distinct pathways.
• A metabolite is a substrate or reactant undergoing a biochemical or metabolic reaction.
• A metabolic reaction is a biochemical reaction where a metabolite is specifically reacted by an enzyme and coenzyme to yield a product.

Types of Metabolic Reactions

• Reversible reactions require the same enzyme and are not regulatory steps.
• Irreversible reactions require a different set of enzymes, are non-equilibrium reactions, and are regulatory steps.

Types of Biochemical Reactions.

• Oxidation/Dehydrogenation/Hydroxylation
• Reduction
• Hydrolytic
• Carboxylation
• Decarboxylation
• Phosphorylation
• Dephosphorylation
• Amination
• Deamination
• Isomerization
• Hydration
• Dehydration
• A metabolic pathway is a series of well-defined and significant biochemical reactions that occur sequentially, yielding intermediate products and a final end product.
• Pathways consist of sequential steps
• Enzymes in pathways can be separate or form a multienzyme complex or a membrane-bound system.
• Multienzyme complexes are more common than previously thought.

Compartmentalization of Pathways

• Permits the integration and regulation of metabolism.
• Cytosol: Glycolysis, Pentose Phosphate Pathway, Fatty Acid Synthesis
• Mitochondrial Matrix: Citric Acid Cycle, Oxidative Phosphorylation, β-Oxidation of Fatty Acids, Ketone-Body Formation
• Interplay of Both Compartments: Gluconeogenesis, Urea Synthesis

Phosphoryl-group Transfer

• Involves compounds like Phosphoenolpyruvate, Phosphocreatine, and Glucose 6-phosphate, playing a role in energy transfer within cells.

Types of Metabolic Pathways

• Catabolic pathways are degradative, energy-generating, and ATP-producing, and are exothermic. They involve oxidative reactions that produce reducing equivalents like NADH+H+ and FADH2, converging to a few end products.
• Anabolic pathways are synthetic, energy-utilizing, and ATP-using, and are endothermic. They diverge to synthesize many biomolecules.
• Some pathways serve in both catabolism and anabolism, known as amphibolic pathways, which occur at the crossroads of metabolism and link anabolic and catabolic pathways.
• Regulation of metabolic pathways involves stimulation and inhibition as per cellular needs.
• Hormones regulate metabolic pathways, allowing the organism to respond to changing conditions.
• Every metabolic pathway has specific regulatory or key enzymes.
• Hormones regulate pathways by stimulating or inhibiting the regulatory/key enzymes.

Modes of Metabolic Regulation

• Allosteric regulation
• Covalent modification
• Control of enzyme levels
• Compartmentalization
• Metabolic specialization of organs

Feedback and Feedforward Mechanisms

• Feedback inhibition occurs when the product of a pathway downregulates the activity of an early step.
• Feedforward activation occurs when a metabolite produced early in the pathway activates a downstream enzyme.
• Anabolic and catabolic pathways involving the same compounds are not identical; some steps may be common to both, but others must differ to ensure spontaneity.
• This difference allows regulation mechanisms to selectively activate one pathway and deactivate the other.

Modes of Enzyme Regulation

• Alteration in membrane permeability.
• Conversion of Inactive to Active form.
• Stimulation of mRNA translation.
• Induction of new mRNA formation.
• Repression of mRNA formation.
• Knowledge of normal metabolism is essential for understanding adaptations to starvation, exercise, pregnancy, lactation, and metabolic disorders.
• Abnormal metabolism can result from nutritional deficiencies, enzyme defects, hormonal defects, and drug/toxin interactions.
• Normal enzyme and hormone activities promote normal metabolism and health; defects in enzymes and hormones disrupt normal metabolism.
• Any defect or derangement in the normal pattern of metabolism results in metabolic disorders.
• Mutation in genes of enzymes leads to the formation of defective enzymes.

Inborn Errors of Metabolism

• Congenital deficiency of a single enzyme in a metabolic pathway leads to inborn errors of metabolism.
• Enzyme deficiency in a metabolic pathway blocks the metabolic reaction and the entire pathway.
• The deficiency leads to the accumulation and excretion of intermediate products, prevents the formation of end products, and affects other interrelated metabolic pathways.

Methods Used to Study Metabolism

• Using whole organism/Cellular fractions
• Using Metabolic Probes.
• Using Radioisotopes.