Dr. Riddhi Datta

Dr. Riddhi Datta

• Metabolism is the sum of all chemical transformations taking place in a cell or organism.

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• It occurs through a series of enzyme-catalyzed reactions that constitute metabolic pathway.

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• In this multistep sequence, the product of one step serves as the substrate for the next step. These metabolic intermediates are called metabolites.

Dr. Riddhi Datta

Multiple metabolic pathways remain interconnected to form a meaningful well-coordinated network that determines the overall functioning of the cell.

Complexity of metabolic pathways as depicted in KEGG: Kyoto Encyclopedia of Genes and Genomes

Dr. Riddhi Datta

Example:

Example:

Dr. Riddhi Datta

• The degradative phase of metabolism
• Organic nutrient molecules (carbohydrates, fats, and proteins) are converted into smaller, simpler end products (such as lactic acid, CO2, NH3)
• Release energy:
• A part is conserved in the form of ATP and reduced electron carriers (NADH, NADPH, and FADH2)
• The rest is lost as heat

• The biosynthetic phase of metabolism
• Small, simple precursors are built up into larger and more complex molecules (lipids, polysaccharides, proteins, and nucleic acids)
• Require input of energy (phosphoryl group transfer potential of ATP and reducing power of NADH, NADPH, and FADH2)

Catabolism

Anabolism

Dr. Riddhi Datta

Some pathways can be either anabolic or catabolic, depending on the energy conditions in the cell. They are referred to as amphibolic pathways.

Example: Citric acid cycle

Dr. Riddhi Datta

Metabolic pathways may linear, branched or cyclic.

Catabolic pathways are convergent and anabolic pathways divergent

(convert several starting materials into a single product)

(yielding multiple useful end products from a single precursor)

(one starting component is regenerated in a series of reactions that converts another starting component into a product)

Dr. Riddhi Datta

Metabolic processes are regulated in three principal ways:

• by controlling the accessibility of substrates
• by controlling the amounts of enzymes
• by controlling their catalytic activities

Dr. Riddhi Datta

Controlling the accessibility of substrates

• At low substrate concentration (near or below K_m), rate of reaction depends on substrate concentration.
• Controlling the flux of substrates also regulates metabolism.
• The transfer of substrates from one compartment of a cell to another (e.g., from the cytosol to mitochondria) can serve as a control point.
• Compartmentalization segregates opposed reactions. For example, fatty acid oxidation takes place in mitochondria, whereas fatty acid synthesis takes place in the cytosol.

Dr. Riddhi Datta

Controlling the amounts of enzymes

• The amount of a particular enzyme depends on:
• its rate of synthesis
• its rate of degradation
• The level of most enzymes is adjusted primarily by changing the rate of transcription of the genes encoding them.

Dr. Riddhi Datta

Controlling their catalytic activities

The catalytic activity of enzymes is controlled by:

• Reversible allosteric control: Key enzymes in many biosynthetic pathways is allosterically inhibited by a metabolic intermediate or coenzyme or the ultimate product of the pathway.
• Reversible covalent modification: Activation/deactivation of enzymes by phosphorylation/deposphorylation of particular residues.
• Hormones-mediated reversible modification of key enzymes: Hormones or growth factors coordinate metabolic relations between different tissues, often by regulating the reversible modification of key enzymes.