Metabolism

Source: Wikipedia, the free encyclopedia.

Set of chemical reactions in organisms

"Cellular metabolism" redirects here. For the journal, see Cell Metabolism.

For the journal 'Metabolism', see Metabolism: Clinical and Experimental. For the architectural movement, see Metabolism (architecture).

Simplified view of the cellular metabolism

Structure of adenosine triphosphate

(ATP), a central intermediate in energy metabolism

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Metabolism (

structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion

and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary (or intermediate) metabolism.

Metabolic reactions may be categorized as

anabolic – the building up (synthesis

) of compounds (such as proteins, carbohydrates, lipids, and nucleic acids). Usually, catabolism releases energy, and anabolism consumes energy.

The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme. Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy and will not occur by themselves, by coupling them to spontaneous reactions that release energy. Enzymes act as catalysts – they allow a reaction to proceed more rapidly – and they also allow the regulation of the rate of a metabolic reaction, for example in response to changes in the cell's environment or to signals from other cells.

The metabolic system of a particular organism determines which substances it will find nutritious and which poisonous. For example, some prokaryotes use hydrogen sulfide as a nutrient, yet this gas is poisonous to animals.^[1] The basal metabolic rate of an organism is the measure of the amount of energy consumed by all of these chemical reactions.

A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species.

type II diabetes, metabolic syndrome, and cancer, normal metabolism is disrupted.^[6] The metabolism of cancer cells is also different from the metabolism of normal cells, and these differences can be used to find targets for therapeutic intervention in cancer.^[7]

Key biochemicals

Further information: Biomolecule, Cell (biology), and Biochemistry

triacylglycerol

lipid

This is a diagram depicting a large set of human metabolic pathways.^{[image reference needed}

]

Most of the structures that make up animals, plants and microbes are made from four basic classes of

macromolecules of life.^[8]

Type of molecule	Name of monomer forms	Name of polymer forms	Examples of polymer forms
Amino acids	Amino acids	Proteins (made of polypeptides)	Fibrous proteins and globular proteins
Carbohydrates	Monosaccharides	Polysaccharides	Starch, glycogen and cellulose
Nucleic acids	Nucleotides	Polynucleotides	DNA and RNA

Amino acids and proteins

Main article: Protein

Proteins are made of

tricarboxylic acid cycle),^[11] especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress.^[12]

Lipids

Main article:

Biolipid

Lipids are the most diverse group of biochemicals. Their main structural uses are as part of

organic solvents such as ethanol, benzene or chloroform.^[13] The fats are a large group of compounds that contain fatty acids and glycerol; a glycerol molecule attached to three fatty acids by ester linkages is called a triacylglyceride.^[14] Several variations on this basic structure exist, including backbones such as sphingosine in sphingomyelin, and hydrophilic groups such as phosphate as in phospholipids. Steroids such as sterol are another major class of lipids.^[15]

Carbohydrates

Glucose can exist in both a straight-chain and ring form.

Main article: Carbohydrate

Carbohydrates are

hydroxyl groups attached, that can exist as straight chains or rings. Carbohydrates are the most abundant biological molecules, and fill numerous roles, such as the storage and transport of energy (starch, glycogen) and structural components (cellulose in plants, chitin in animals).^[10] The basic carbohydrate units are called monosaccharides and include galactose, fructose, and most importantly glucose. Monosaccharides can be linked together to form polysaccharides in almost limitless ways.^[16]

Nucleotides

Main article: Nucleotide

The two nucleic acids, DNA and

heterocyclic rings containing nitrogen, classified as purines or pyrimidines. Nucleotides also act as coenzymes in metabolic-group-transfer reactions.^[18]

Coenzymes

acetyl group

is bonded to the sulfur atom at the extreme left.

One central coenzyme is adenosine triphosphate (ATP), the energy currency of cells. This nucleotide is used to transfer chemical energy between different chemical reactions. There is only a small amount of ATP in cells, but as it is continuously regenerated, the human body can use about its own weight in ATP per day.^[20] ATP acts as a bridge between catabolism and anabolism. Catabolism breaks down molecules, and anabolism puts them together. Catabolic reactions generate ATP, and anabolic reactions consume it. It also serves as a carrier of phosphate groups in phosphorylation reactions.^[21]

A

The structure of iron-containing hemoglobin. The protein subunits are in red and blue, and the iron-containing heme groups in green. From PDB: 1GZX

​.

Inorganic elements play critical roles in metabolism; some are abundant (e.g. sodium and potassium) while others function at minute concentrations. About 99% of a human's body weight is made up of the elements carbon, nitrogen, calcium, sodium, chlorine, potassium, hydrogen, phosphorus, oxygen and sulfur. Organic compounds (proteins, lipids and carbohydrates) contain the majority of the carbon and nitrogen; most of the oxygen and hydrogen is present as water.^[25]

The abundant inorganic elements act as

Transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant of those.^[29] Metal cofactors are bound tightly to specific sites in proteins; although enzyme cofactors can be modified during catalysis, they always return to their original state by the end of the reaction catalyzed. Metal micronutrients are taken up into organisms by specific transporters and bind to storage proteins such as ferritin or metallothionein when not in use.^[30][31]

Catabolism

Catabolism is the set of metabolic processes that break down large molecules. These include breaking down and oxidizing food molecules. The purpose of the catabolic reactions is to provide the energy and components needed by anabolic reactions which build molecules.

The most common set of catabolic reactions in animals can be separated into three main stages. In the first stage, large organic molecules, such as proteins, polysaccharides or lipids, are digested into their smaller components outside cells. Next, these smaller molecules are taken up by cells and converted to smaller molecules, usually acetyl coenzyme A (acetyl-CoA), which releases some energy. Finally, the acetyl group on acetyl-CoA is oxidized to water and carbon dioxide in the citric acid cycle and electron transport chain, releasing more energy while reducing the coenzyme nicotinamide adenine dinucleotide (NAD⁺) into NADH.^[32]

Digestion

Macromolecules cannot be directly processed by cells. Macromolecules must be broken into smaller units before they can be used in cell metabolism. Different classes of enzymes are used to digest these polymers. These

Microbes simply secrete digestive enzymes into their surroundings,[37]^[38] while animals only secrete these enzymes from specialized cells in their guts, including the stomach and pancreas, and in salivary glands.^[39] The amino acids or sugars released by these extracellular enzymes are then pumped into cells by active transport proteins.^[40][41]

A simplified outline of the catabolism of proteins, carbohydrates and fats^{[image reference needed}

]

Fats are catabolized by hydrolysis to free fatty acids and glycerol. The glycerol enters glycolysis and the fatty acids are broken down by beta oxidation to release acetyl-CoA, which then is fed into the citric acid cycle. Fatty acids release more energy upon oxidation than carbohydrates. Steroids are also broken down by some bacteria in a process similar to beta oxidation, and this breakdown process involves the release of significant amounts of acetyl-CoA, propionyl-CoA, and pyruvate, which can all be used by the cell for energy. M. tuberculosis can also grow on the lipid cholesterol as a sole source of carbon, and genes involved in the cholesterol-use pathway(s) have been validated as important during various stages of the infection lifecycle of M. tuberculosis.^[45]

In oxidative phosphorylation, the electrons removed from organic molecules in areas such as the citric acid cycle are transferred to oxygen and the energy released is used to make ATP. This is done in eukaryotes by a series of proteins in the membranes of mitochondria called the electron transport chain. In prokaryotes, these proteins are found in the cell's inner membrane.^[49] These proteins use the energy from reduced molecules like NADH to pump protons across a membrane.^[50]

Mechanism of ATP synthase

. ATP is shown in red, ADP and phosphate in pink and the rotating stalk subunit in black.

Pumping protons out of the mitochondria creates a proton concentration difference across the membrane and generates an electrochemical gradient.^[51] This force drives protons back into the mitochondrion through the base of an enzyme called ATP synthase. The flow of protons makes the stalk subunit rotate, causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate – turning it into ATP.^[20]

Energy from inorganic compounds

The energy in sunlight is captured by plants, cyanobacteria, purple bacteria, green sulfur bacteria and some protists. This process is often coupled to the conversion of carbon dioxide into organic compounds, as part of photosynthesis, which is discussed below. The energy capture and carbon fixation systems can, however, operate separately in prokaryotes, as purple bacteria and green sulfur bacteria can use sunlight as a source of energy, while switching between carbon fixation and the fermentation of organic compounds.^[58][59]

In many organisms, the capture of solar energy is similar in principle to oxidative phosphorylation, as it involves the storage of energy as a proton concentration gradient. This proton motive force then drives ATP synthesis.^[60] The electrons needed to drive this electron transport chain come from light-gathering proteins called photosynthetic reaction centres. Reaction centers are classified into two types depending on the nature of photosynthetic pigment present, with most photosynthetic bacteria only having one type, while plants and cyanobacteria have two.^[61]

In plants, algae, and cyanobacteria, photosystem II uses light energy to remove electrons from water, releasing oxygen as a waste product. The electrons then flow to the cytochrome b6f complex, which uses their energy to pump protons across the thylakoid membrane in the chloroplast.^[34] These protons move back through the membrane as they drive the ATP synthase, as before. The electrons then flow through photosystem I and can then be used to reduce the coenzyme NADP⁺.^[62] This coenzyme can enter the Calvin cycle, which is discussed below, or be recycled for further ATP generation.^{[citation needed]}

Anabolism

Anabolism is the set of constructive metabolic processes where the energy released by catabolism is used to synthesize complex molecules. In general, the complex molecules that make up cellular structures are constructed step-by-step from smaller and simpler precursors. Anabolism involves three basic stages. First, the production of precursors such as amino acids, monosaccharides, isoprenoids and nucleotides, secondly, their activation into reactive forms using energy from ATP, and thirdly, the assembly of these precursors into complex molecules such as proteins, polysaccharides, lipids and nucleic acids.^[63]

Anabolism in organisms can be different according to the source of constructed molecules in their cells. Autotrophs such as plants can construct the complex organic molecules in their cells such as polysaccharides and proteins from simple molecules like carbon dioxide and water. Heterotrophs, on the other hand, require a source of more complex substances, such as monosaccharides and amino acids, to produce these complex molecules. Organisms can be further classified by ultimate source of their energy: photoautotrophs and photoheterotrophs obtain energy from light, whereas chemoautotrophs and chemoheterotrophs obtain energy from oxidation reactions.^[63]

Carbon fixation

Plant cells (bounded by purple walls) filled with chloroplasts (green), which are the site of photosynthesis

In photosynthetic prokaryotes the mechanisms of carbon fixation are more diverse. Here, carbon dioxide can be fixed by the Calvin – Benson cycle, a reversed citric acid cycle,^[66] or the carboxylation of acetyl-CoA.^[67][68] Prokaryotic chemoautotrophs also fix CO₂ through the Calvin–Benson cycle, but use energy from inorganic compounds to drive the reaction.^[69]

Carbohydrates and glycans

In carbohydrate anabolism, simple organic acids can be converted into