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An Introduction to Metabolism

The cells in our bodies are constantly busy, whether we are awake, sleeping, running or watching TV. Thousands of chemical reactions that are essential for the proper functioning of cells as well as the body as a whole are constantly taking place. These chemical reactions lead to the provision of energy and are referred to as "metabolism". Metabolism also encompasses the reactions that use this energy for the vital processes of synthesizing new organic material.


In fact, metabolism includes almost all enzyme-catalyzed reactions, from the uptake of nutrients to excretions of waste products. The reactions involved are so diverse that it would not be possible to provide an exhaustive list. However, generally, they are divided into degradative reactions - catabolism, and synthetic reactions - anabolism.


Anabolism


Anabolism involves the synthesis of complex molecules from simpler ones. As energy is stored in chemical bonds, anabolic reactions are energy-consuming processes, known as endergonic reactions.


A classic example is building glucose from carbon dioxide via photosynthesis. Photosynthetic organisms, such as plants and algae, directly make use of solar energy by trapping it as organic carbon compounds. In contrast, non-photosynthetic organisms, like ourselves, cannot directly harness solar energy, therefore, they depend on carbon trapped by photosynthetic organisms. Hence, the sun is considered the ultimate energy for metabolism in all organisms. Photosynthesis takes place in many small steps, but its overall reaction is:

6CO2 + 6H2O + Energy → C6H12O6 + 6O2



Other examples include the synthesis of proteins from amino acids and DNA strands from nucleotides. It is worth noting that the production of amino acids and nucleotides themselves are also part of anabolism.


Catabolism


On the other hand, catabolism is the breakdown of complex molecules into simpler ones. This process releases energy, thus is referred to as exergonic reactions. Many cells in your body get energy from glucose in a process called cellular respiration. During this process, each glucose molecule is broken down gradually. However, the process has an overall reaction of:

C6H12O6 + 6O2 → 6H2O + 6CO2 + Energy


Breaking down glucose releases energy, which is captured by the cell in the form of adenosine triphosphate, or ATP. As a small molecule, ATP is a mobile energy source. Thus, it is used to drive many vital reactions inside cells.

Figure 1: The energy storage molecule, adenosine triphosphate (ATP). ATP consists of a ribose sugar, an adenine base and three phosphates linked by high energy phosphoanhydride bonds. The hydrolysis of these phosphoanhydride bonds releases the chemical energy stored.


Catabolism is generally divided into three stages:


a. Digestion

This stage involves the breakdown of biological polymers into their corresponding small monomeric units. Consider the biological macromolecules, carbohydrates are broken down into monosaccharides such as glucose, proteins into amino acids, lipids into fatty acids and glycerol, and nucleic acids (DNA and RNA) into nucleotides.


b. Release of energy

Once the polymers are broken down, the constituent monomers are taken up by cells and converted to yet smaller molecules such as pyruvate and acetate. Pyruvate, in turn, is used to generate acetyl CoA, which enters crucial metabolic pathways such as the citric acid cycle for the release of energy.


c. Storage of energy

The energy released is stored in two main ways. It can be stored by reducing the nicotinamide adenine dinucleotide (NAD+) into NADH. As a coenzyme (a molecule that binds to and assists the function of enzymes) NADH supplies reducing equivalents to the mitochondrial electron transport chain. This leads to the production of ATP, the other type of energy storage. Even though ATP is mainly produced through the electron transport chain, some of the chemical energy released in the citric acid cycle is also directly captured in ATP.


In addition to the citric acid cycle, catabolic processes also include glycolysis, the breakdown of muscle protein, and the breakdown of fat in adipose tissue to fatty acids.


Metabolism of key biological molecules


Carbohydrate metabolism

Carbohydrate metabolism includes a myriad of catabolic and anabolic processes that ensure the constant supply of energy to cells. Central to carbohydrate metabolism, however, is the sugar glucose.


Glucose metabolism

When we consume carbohydrates, they are broken down into glucose, which is in turn phosphorylated in the cells producing glucose-6-phosphate. This metabolite is used in almost every metabolic process. A prominent example is glycolysis, a catabolic process that releases energy. This process uses glucose to generate two molecules of pyruvate, which has two fates. It can be taken into the mitochondria, where it can generate acetyl-CoA. As previously mentioned, acetyl-CoA enters the citric acid cycle and oxidative phosphorylation, ultimately producing ATP. It can also remain in the cell to be used in gluconeogenesis. Here, pyruvate is converted back to glucose via a series of intermediates. This latter fate is important under fasting conditions where a fresh supply of glucose is lacking.


Glucose storage

Glucose can also be stored as glycogen granules, which is a polymer of glucose and has a tree-like structure. Some tissues, like the liver, use glycogen to maintain stable blood glucose levels. Glycogen is also essential for the quick mobilization of glucose. For example, during an anaerobic activity such as heavy lifting, your body requires immediate energy. Hence, your body relies on glucose, and thus its associated energy, stored in glycogen to fuel itself. To facilitate this, skeletal muscles can also store up to 500 g of glycogen.


Regulation of carbohydrate metabolism

Carbohydrate metabolism is regulated mainly by the hormone insulin, as it stimulates glycolysis and glycogenesis (the synthesis of glycogen). Because of the central role of carbohydrate metabolism throughout the body, an imbalance in insulin can cause multiple diseases.


Under normal circumstances, the amount of glucose in the blood increases after a meal, triggering the release of insulin from the pancreas. This stimulates muscle and fat cells to remove glucose from the blood and the liver to metabolize glucose, returning the blood sugar level to normal. However, when there is little to no production of insulin, the blood sugar levels will remain high, leading to conditions such as diabetes.


Fatty acid metabolism

Fatty acids are noteworthy as a major component of phospholipids, which largely makes up cell membranes. However, like carbohydrates, fatty acids are also involved in energy production, albeit via different pathways. Fatty acids are broken down into acetyl CoA via β oxidation. The acetyl CoA is then oxidized by the same citric acid cycle involved in the metabolism of glucose. For every two carbons in a fatty acid molecule, 5 ATPs are generated from the oxidation of NADH and FADH2 via the electron transport chain and 10 more ATPs from oxidizing acetyl CoA. Hence, the length of the fatty acid chain determines the amount of energy generated.


Amino acid metabolism

Amino acids are the building blocks of proteins. There are 20 common amino acids, some of which are essential, meaning that the body cannot synthesize them, and must obtain them from the diet; whilst others are non-essential amino acids, which can be synthesized by the human body.


Synthesis of non-essential amino acids

Non-essential amino acids are synthesized from intermediates in the major metabolic pathways. The carbon skeletons of these amino acids are traceable to their corresponding α-keto acids. Therefore, if the keto acid exists as a common intermediate it could be possible to synthesize one of the non-essential amino acids directly by transferring an amino group (NH3+) from another amino acid to the keto acid. This reaction is known as transamination and will be discussed further in the following section. Examples of such α-keto acids intermediates are pyruvate (glycolytic end product), oxaloacetate and α-ketoglutarate (citric acid cycle intermediates).


Degradation of amino acids

The reverse occurs during the degradation of amino acids, where amino acids are first broken down into their corresponding α-keto acids. The same transamination reactions occur in the opposite direction. Furthermore, transamination is catalysed by aminotransferases specific to different amino acids. For instance, alanine aminotransferase transfers the amino group from the amino acid alanine to α-ketoglutarate, producing pyruvate and glutamate. Aspartate aminotransferase, by contrast, transfers the amino group from aspartate to α-ketoglutarate, producing oxaloacetate and glutamate.

Figure 2: Transamination of a. Alanine and b. Aspartate. Aminotransferases catalyses the transfer of the amino group (NH3+) from an amino acid to a keto acid. Depending on the direction of this reaction, this facilitates either amino acid synthesis (reverse) degradation (forward). This figure was adapted from Vroon & Israili, 1990.


You may have noticed that both these reactions produce the amino acid glutamate. Indeed, in the following reaction, deamination, glutamate is broken down into α-ketoglutarate and ammonia. However, free ammonia is a toxic molecule, especially for the central nervous system. Therefore, it needs to be converted to urea in the liver via the catabolic urea cycle for excretion.

Figure 3: Deamination of the amino acid glutamate catalysed by glutamate dehydrogenase. This figure was adapted from Berg et al., 2002.


Concluding remarks

Generally, metabolism goes in two main directions. The first is to convert food/fuels into energy for the cells and organisms for them to carry out their activities. Secondly, provide building blocks for the synthesis of the macromolecules such as carbohydrates, proteins, lipids and nucleic acids which are important for growth and propagation.


Dysfunction of certain steps in metabolism can lead to serious metabolic disease including diabetes. Here we illustrated some examples of the molecular pathways involved and the principle of energy conversion. However, metabolism in the human body involves many tightly regulated, interconnected pathways and requires the cooperation of cells in different organs. An understanding of metabolism truly provides much insight into how the body functions and to develop potential treatments for related diseases.


Author


Idris Adekale

MSc Biotechnology

Bayero University Kano, Nigeria


Illustrator


Amy Cheng

BSc Biochemistry

Imperial College London


#Metabolism#Catabolism#Anabolism



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