Metabolic Pathways

Metabolic pathways are series of consecutive enzymatic reactions that produce specific products. Their reactants, intermediates and products are referred to as metabolites. Since an organism utilizes many metabolites, it has many metabolic pathways.

Each reaction in metabolic pathways are catalyzed by a distinct enzyme, of which there are more than 2000 known. At first glance, this network seems hopelessly complex.

The reaction pathways that comprise metabolism are often divided into two categories. Those involved in degradation- Catabolism and those involved in biosynthesis- Anabolism.

In Catabolism pathways, complex metabolites are exergonically broken down to simpler products.The free energy released during these processes is conserved by the synthesis of ATP from ADP and phosphate or by the reduction of the coenzyme NADP+ to NADPH.

ATP and NADPH are the major free energy sources for anabolic pathways.

A striking characteristic of degradative metabolism is that it converts a large number of diverse substances (carbohydrates,lipids and proteins) to common intermediates. These intermediates are then further metabolized in a central oxidative pathway that terminates in a few end products. 

Proteins into amino acids; carbohydrates into glucose and lipids into fatty acids & glycerol, then to common intermediate acetyl coenzyme A. This is followed by the oxidation of the acetyl group to CO2 and H2O by the sequential actions of  citric acid cycle, the electron transport chain and oxidative phosphorylation.

Biosynthesis carries out the opposite process. Relatively few metabolities, mainly pyruvate, acetyl Co A and the Citric acid cycle intermediates, serve as starting materials for a host of varied biosynthetic products.

Four principal characteristics of metabolic pathways stem from their function of generating products for use by the cell:

1- Metabolic pathways are irreversible:

They are highly exergonic(have large negative free energy changes), so their reactions go to completion. This characteristic provides the pathway with direction. Consequently, if two metabolites are metabolically interconvertible , the pathway from the first to the second must differ from the pathways from the second back to the first.

The reason for this difference is that if the route from the first metabolite to the second is exergonic, free energy must be supplied in order to bring it “back up the hill”. This required a different pathway for at least some of the reaction steps. The existence of independent interconversion routes is an important property of metabolic pathways because it allows independent control of the rate of the two processes.

If metabolite 2 is required by the cell, it is necessary to “turn off” the pathway from 2 to 1 while “turning on “ the pathway from 1 to 2. Such independent control would be impossible without different pathways.

2- Every metabolic pathway has a first committed step:

Although metabolic pathways are irreversible, most of their component reactions function close to equilibrium. Early in each pathway, however, there is generally an irreversible (exergonic) reaction that “commits” the intermediate it produces to continue down the pathway.

3-All metabolic pathways are regulated:

In order to exert control on the flux of metabolites through a metabolic pathways, it is necessary to regulate its rate limiting step. The first committed step, being irreversible, functions too slowly to permit its substrates and products to equilibrate. Since most of the other reactions in a pathway function close to equilibrium , the first committed step is often its rate limiting step. Most metabolic pathways are therefore controlled by regulating the enzyme that catalyze their first committed steps. This is the most efficient way to exert control because it prevents the unnecessary synthesis of metabolites further along the pathway when they are not required.

4-Metabolic pathways in eukaryotic cells occur in specific cellular locations

The synthesis of metabolites in specific membrane bounded subcellular compartments makes their transport between these compartments a vital component of eukaryotic metabolism. Biological membranes are selectively permeable to metabolites because of the presence of in membranes of specific transport proteins.

For example, ATP is generated in the mitochondria but much of it is utilized in the cytosol.

The synthesis and utilization of acetyl-CoA is also compartmentalized . This metabolic intermediate is utilized in the cytosolic synthesis of fatty acids, but is synthesized in mitochondria.

Yet there is  no transport protein for acetyl CoA in the mitochondrial membrane.