, a metabolic pathway is a linked series of chemical reaction
s occurring within a cell
. The reactant
s, products, and intermediates of an enzymatic reaction are known as metabolites
, which are modified by a sequence of chemical reactions catalyze
d by enzyme
In most cases of a metabolic pathway, the product
of one enzyme acts as the substrate
for the next. However, side products are considered waste and removed from the cell. These enzymes often require dietary minerals, vitamins, and other cofactors
Different metabolic pathways function based on the position within a eukaryotic cell and the significance of the pathway in the given compartment of the cell. For instance, the, electron transport chain
, and oxidative phosphorylation
all take place in the mitochondrial membrane.
In contrast, glycolysis
, pentose phosphate pathway
, and fatty acid biosynthesis
all occur in the cytosol
of a cell.
There are two types of metabolic pathways that are characterized by their ability to either synthesize molecules with the utilization of energy (anabolic pathway
), or break down complex molecules and release energy in the process (catabolic pathway
The two pathways complement each other in that the energy released from one is used up by the other. The degradative process of a catabolic pathway provides the energy required to conduct the biosynthesis of an anabolic pathway.
In addition to the two distinct metabolic pathways is the amphibolic pathway, which can be either catabolic or anabolic based on the need for or the availability of energy.
Pathways are required for the maintenance of homeostasis
within an organism
and the flux
of metabolites through a pathway is regulated depending on the needs of the cell and the availability of the substrate. The end product of a pathway may be used immediately, initiate another metabolic pathway or be stored for later use. The metabolism
of a cell consists of an elaborate network
of interconnected pathways that enable the synthesis and breakdown of molecules (anabolism and catabolism).
Each metabolic pathway consists of a series of biochemical reactions that are connected by their intermediates: the products of one reaction are the substrates
for subsequent reactions, and so on. Metabolic pathways are often considered to flow in one direction. Although all chemical reactions are technically reversible, conditions in the cell are often such that it is thermodynamically
more favorable for flux
to proceed in one direction of a reaction. For example, one pathway may be responsible for the synthesis of a particular amino acid, but the breakdown of that amino acid may occur via a separate and distinct pathway. One example of an exception to this "rule" is the metabolism of glucose
results in the breakdown of glucose, but several reactions in the glycolysis pathway are reversible and participate in the re-synthesis of glucose (gluconeogenesis
was the first metabolic pathway discovered:
enters a cell, it is immediately phosphorylated
to glucose 6-phosphate
in the irreversible first step.
#In times of excess lipid
energy sources, certain reactions in the glycolysis
pathway may run in reverse to produce glucose 6-phosphate
, which is then used for storage as glycogen
* Metabolic pathways are often regulated
by feedback inhibition
* Some metabolic pathways flow in a 'cycle' wherein each component of the cycle is a substrate for the subsequent reaction in the cycle, such as in the Krebs Cycle
pathways in eukaryotes
often occur independently of each other, separated either physically by compartmentalization within organelles
or separated biochemically by the requirement of different enzymes and co-factors.
Major metabolic pathways
Catabolic pathway (catabolism)
A catabolic pathway
is a series of reactions that bring about a net release of energy in the form of a high energy phosphate bond formed with the energy carriers adenosine diphosphate (ADP) and guanosine diphosphate (GDP) to produce adenosine triphosphate (ATP) and guanosine triphosphate (GTP), respectively.
The net reaction is, therefore, thermodynamically favorable, for it results in a lower free energy for the final products.
A catabolic pathway is an exergonic system that produces chemical energy in the form of ATP, GTP, NADH, NADPH, FADH2, etc. from energy containing sources such as carbohydrates, fats, and proteins. The end products are often carbon dioxide, water, and ammonia. Coupled with an endergonic reaction of anabolism, the cell can synthesize new macromolecules using the original precursors of the anabolic pathway. An example of a coupled reaction is the phosphorylation of fructose-6-phosphate
to form the intermediate fructose-1,6-bisphosphate
by the enzyme phosphofructokinase
accompanied by the hydrolysis of ATP in the pathway of glycolysis
. The resulting chemical reaction within the metabolic pathway is highly thermodynamically favorable and, as a result, irreversible in the cell.
Fructose-6-Phosphate + ATP -> Fructose-1,6-Bisphosphate + ADP
A core set of energy-producing catabolic
pathways occur within all living organisms in some form. These pathways transfer the energy released by breakdown of nutrient
s into ATP
and other small molecules used for energy (e.g. GTP
). All cells can perform anaerobic respiration
. Additionally, most organisms can perform more efficient aerobic respiration
through the citric acid cycle
and oxidative phosphorylation
. Additionally plant
are able to use sunlight to anabolic
ally synthesize compounds from non-living matter by photosynthesis
Anabolic pathway (anabolism)
In contrast to catabolic pathways, anabolic pathways
require an energy input to construct macromolecules such as polypeptides, nucleic acids, proteins, polysaccharides, and lipids. The isolated reaction of anabolism is unfavorable in a cell due to a positive Gibbs Free Energy
(+Δ''G''). Thus, an input of chemical energy through a coupling with an exergonic reaction
The coupled reaction of the catabolic pathway affects the thermodynamics of the reaction by lowering the overall activation energy of an anabolic pathway and allowing the reaction to take place.
Otherwise, an endergonic reaction
An anabolic pathway is a biosynthetic pathway, meaning that it combines smaller molecules to form larger and more complex ones.
An example is the reversed pathway of glycolysis, otherwise known as gluconeogenesis
, which occurs in the liver and sometimes in the kidney to maintain proper glucose concentration in the blood and supply the brain and muscle tissues with adequate amount of glucose. Although gluconeogenesis is similar to the reverse pathway of glycolysis, it contains three distinct enzymes from glycolysis that allow the pathway to occur spontaneously. An example of the pathway for gluconeogenesis is illustrated in the image titledGluconeogenesis Mechanism
An amphibolic pathway
is one that can be either catabolic or anabolic based on the availability of or the need for energy.
The currency of energy in a biological cell is adenosine triphosphate (ATP)
, which stores its energy in the phosphoanhydride bonds
. The energy is utilized to conduct biosynthesis, facilitate movement, and regulate active transport inside of the cell.
Examples of amphibolic pathways are the citric acid cycle and the glyoxylate cycle. These sets of chemical reactions contain both energy producing and utilizing pathways.
To the right is an illustration of the amphibolic properties of the TCA cycle.
The glyoxylate shunt pathway
is an alternative to the tricarboxylic acid (TCA) cycle
, for it redirects the pathway of TCA to prevent full oxidation of carbon compounds, and to preserve high energy carbon sources as future energy sources. This pathway occurs only in plants and bacteria and transpires in the absence of glucose molecules.
The flux of the entire pathway is regulated by the rate-determining steps.
These are the slowest steps in a network of reactions. The rate-limiting step occurs near the beginning of the pathway and is regulated by feedback inhibition, which ultimately controls the overall rate of the pathway. The metabolic pathway in the cell is regulated by covalent or non-covalent modifications. A covalent modification involves an addition or removal of a chemical bond, whereas a non-covalent modification (also known as allosteric regulation) is the binding of the regulator to the enzyme via hydrogen bond
s, electrostatic interactions, and Van Der Waals forces
The rate of turnover in a metabolic pathway, also known as the metabolic flux
, is regulated based on the stoichiometric reaction model, the utilization rate of metabolites, and the translocation pace of molecules across the lipid bilayer
The regulation methods are based on experiments involving 13C-labeling
, which is then analyzed by Nuclear Magnetic Resonance (NMR)
or gas chromatography-mass spectrometry (GC-MS)
-derived mass compositions. The aforementioned techniques synthesize a statistical interpretation of mass distribution in proteinogenic amino acid
s to the catalytic activities of enzymes in a cell.
*Metabolic network modelling
Full map of metabolic pathwaysOverview Map from BRENDABioCyc: Metabolic network models for thousands of sequenced organismsKEGG: Kyoto Encyclopedia of Genes and GenomesReactome, a database of reactions, pathways and biological processesMetaCyc: A database of experimentally elucidated metabolic pathways (2,200+ pathways from more than 2,500 organisms).MetaboMAPS: A platform for pathway sharing and data visualization on metabolic pathwaysThe Pathway Localization database (PathLocdb)DAVID: Visualize genes on pathway mapsWikipathways: pathways for the peopleConsensusPathDB''metpath'': Integrated interactive metabolic chart