Proteins: Nature’s Nano-Machines

The summery below is for educational purposes only. The text is adapted in most part from the book Prof. Nir Ben-Tal and I wrote, Introduction to Proteins: Structure, Function, & Motion [Book’s web-page with downlodable materials]:


The book discusses protein structure & function while referring to many everyday applications of protein science, such as disease & cure, drugs of abuse, toxinsindustrial engineering and much more. 

There are few pictures/animations in this page which are not taken from the book, but rather from other freely accessible websites. Links to these sources are given



Proteins are very common molecules in living organisms. For example, the body of a 70 kg man contains ~ 11 kg protein, 43% of which is in skeletal muscles, ~30% in skin & blood, and only relatively small amounts are present in the other tissues and organs (brain, liver, kidneys, lungs, heart, bones, etc). Although there are many different types of proteins in our body, ~50% of them belong to a small group: actin & myosin (muscle proteins), collagen (the major protein in connective tissues) and hemoglobin (a red blood cell protein that transfers oxygen and CO2 between the lungs and peripheral tissues).

Proteins are not only common, they are also the most functionally-diverse molecules in living organisms. Here are some examples of the most common functions of proteins:


1. Enzymes

In each cell of each living organism there are thousands of chemical reactions occurring at the same time. These reactions allow the cell to extract energy from foodstuff, build complex materials, breakdown toxic waste, synthesize an enormous group of biologically  active molecules, transfer signals inside and outside the cell, and more. Most of these reactions happen readily, but very slowly (up to thousands of years!). This is in contrast to cellular needs, which require the reactions to happen within a time scale of nanosecond to millisecond to sustain life. Thus, virtually all biological reactions are catalyzed, i.e. accelerated by a catalyst. In essence  reaction catalysis can be carried out by simple metals. However, these simple elements accelerate reaction non-specifically. That is, they may help convert the reactant into a different product than intended, as well as serve as catalysts in reactions which involve other reactants. Also, the rate of acceleration cannot be influenced or regulated in the case of simple metal catalysts. Some proteins, termed enzymes, are able to act as catalysts of chemical reactions. However, in contrast to the simple metal catalysts, enzymes accelerate reactions in a highly specific manner and can also be efficiently regulated. For this reason, proteins have been selected by evolution as the principle catalysts in all biological organisms. The highly specific catalysis applied by enzymes allow the thousands of chemical reactions within each cell to occur without any of them interfering with the others. Furthermore, cells regulate the rate of their enzymes in different ways, mainly by using small molecules which bind to enzymes and either increase or decrease their activity (activators and inhibitors, respectively).

A simple animation showing how an enzyme (yellow shape) accelerates a chemical reaction which break a reactant molecule into two product molecules (source). Click image to watch the animation

Here is another animation demonstrating enzyme action.

DNA replicationEnzyme action during DNA replication (source)


2. Cell-Surface Receptors

Many proteins residing on/within the cellular membrane of the cell are involved in cell-cell signaling. These proteins know how bind messenger molecules coming from other cells and relay their message into the cell via the activation of intra-cellular proteins/enzymes. The outcome of such messages may be the synthesis of certain molecules, growth or division of the cell, and even its death by suicide (a.k.a. apoptosis) (e.g. when it has been infected with a virus).


Signal  pathways resulting from the activation of different receptors (source). Click to enlarge.

Membrane-bound protein receptors come in different sizes and shapes. Some of them, like the receptors which relay the signals of hormones and neurotransmitters in our body, are made of one protein chain that crosses the membrane 7 times. These are called G-protein-coupled receptors, or GPCRs. Others, like the receptors which respond to the signals of growth factors, are made of two protein chains, each crossing the membrane once (see figure below).

The 3D structure of some cell-surface receptors that cross the membrane twice (source)

Not all protein receptors are located on the cell’s membrane. For example, receptors that relay the signals of steroid messengers, reside inside the cell. After their cognate messenger molecule (steroid) has entered the cell and attached to them, these protein recptors help it bind specifically to a genetic element in the cell’s nuclear DNA. This changes gene expression within the cell, which often leads to long-lived changes. More on cellular signalling and receptors can be found here.


3. Chemical Messengers

Certain short protein segments, termed peptides,act as chemical messengers which bind to cell-surface receptors and induce various changes in cellular behavior. For example, a peptide called vasopressin is secreted from cells in the pituitary gland of animals following dehydration or blood loss, and affects different cells in the body. Its effect on kidney cells decreases water loss during urine formation, whereas its effect on smooth muscle cells around arteries leads to their contraction and, as a result, elevation of blood pressure.

The atomic structure of vasopressin (source)


4. Transport Proteins

Some proteins embedded within the plasma membrane of cells allow the entry and/or exit of different molecules in a highly regulated manner. These proteins therefore control the chemical composition of the cell. Some transport proteins are shaped as narrow channels and function in the transport of small ions in and out of the cell. Others, having a more complex structure, transport larger molecules like sugars and amino acids. These are called ‘carriers‘. While protein channels can only transport ions down their electro-chemical gradient (‘passive transport‘), some carriers are able to transport atoms/molecules up their gradient (see figure below). These transporters are called ‘pumps‘, and their transport activity is called ‘active transport‘, since it requires energy. The energy may be supplied directly by breaking down ATP, or indirectly, by coupling the energy released from the transport of a second atom/molecule down its gradient, to the energy-requiring transport process. More on cellular transporters can be found here.

Active vs. passive transport of solutes (source)

5. Structural Elements

Unlike enzymes, receptors and transporters, some proteins play more passive roles, as building blocks of much larger structures inside and outside the cell. The most important of these structures are the cytoskeleton, which resides in the inner periphery of the cell, and the extra-cellular matrix, which resides outside the cell.

The cytoskeleton (yellow & blue strands) extending from the cell nucleus (pink sphere) to the periphery of the cell (source)


Being so functionally diverse, proteins play a central role in virtually all physiological processes. This includes the execution of our body’s genetic plan, defending our body against bacteria, viruses, and toxins, transporting oxygen, facilitating hormonal and neural communication, keeping our blood pressure steady, and building cells and tissues.

Accordingly, when proteins are damaged by a mutation, infective agent, or toxin, this may lead to a serious disease. For example, the protein p53 is activated when our DNA is harmed by radiation. p53 prevents the cell from dividing until the damaged DNA is repaired. When p53 itself is damaged, the cell usually becomes cancerous. In fact, about 50% of tumors contain a damaged p53. It is no surprise then, that most of the major molecular targets of prescription drugs are proteins. For example, the well-known painkiller and fever-reducing drug Ibuprofen:


Ibuprofen (as well as other members of the Non-Steroidal Anti-Inflammatory Drugs family) works by neutralizing a protein-enzyme called COX, which produces pain- and fever-causing chemicals in our body. The image below shows the structure of COX (red-green-gray ribbon) bound to ibuprofen (spheres):

COX-Ibuprofen complex2


Proteins are also targeted by drugs of abuse. For example, the narcotic drug heroin (a synthetic mimic of opium-derived morphine) acts by binding to a protein receptor in the brain, which normally responds to our body’s natural painkillers, endorphins. This way, the drug induces euphoria and reduced pain sensation. However, in contrast to the natural endorphins, heroin is highly addictive and harms our body.



Drugs are not the only molecules that can bind to proteins. In fact, virtually all protein functions require them to bind other molecules. These are called “ligands” in general. Ligand are functionally diverse: they may act as the substrate of a protein (enzyme), a regulator that is released by the cell to speed up or slow down the activity of the protein, as chemical messengers (e.g. hormones), and more. Ligands are also very diverse chemically: they may be small organic molecules, lipids, sugars, DNA, and even proteins and peptides.

Proteins bind their ligands using a pocket-like indentation on their surface, called “binding site” or “active site” (when the pocket is also the site where enzymatic catalysis takes place). Protein binding sites come in many shapes and chemical compositions, to match the diversity of ligands. For example, if the ligand is a small molecule, the binding site will be small and narrow, whereas a binding site for a ligand that is itself a protein is often large and flat. The image below shows the geometric and chemical match of a metabolic enzyme (LDH) active site and its ligand:

Binding pocket

*(click on figure to view animation)

The match between the protein binding site and the ligand results from the ability of the  protein to position specific chemical groups around the ligand at certain distances and angles (see figure below). These groups interact with the atoms of the ligand, thus making it stay bound to the protein. In enzymes, the chemical groups interacting with ligand (called here ‘substrate’) also act chemically on it, which induces catalysis of the substrate into a product (i.e. a different molecule). As will be explained below, the positions of all key chemical groups in the protein are set by its 3D structure.

Physical interactions between ligand (green) and the chemical groups in the active site of an enzyme.



Amino acids and the peptide bond

(For more details on amino acids, see following section)

Proteins are long polymers of amino acids, all of which having the same general chemical structure:

The general structure of an amino acid. 

There are 20 types of natural amino acids, each having a unique side-chain (R group):

The 20 types of amino acids. The side chains are marked by pink rectangles. (taken from Lehninger’s biochemistry book)


The 20 naturally occurring amino acids can be clustered according to their physical-chemical properties, as shown in the following Venn diagram:

Venn diagram

The 20 natural amino acids clustered by their physical-chemical properties (taken from Esquivel et al. (2013))


Some proteins also contain amino acid derivates (a.k.a. ‘non-natural amino acids’). For example, collagen, a protein that is widespread in animal connective tissues, contains hydroxyproline and hydroxylysine. These are produced by attachment of a hydroxyl group to the natural amino acids proline and lysine, respectively. Another non-natural amino acid, γ-carboxyglutamate, is formed by attachment of a carboxyl group to the amino acid glutamate in blood-clotting proteins. All of the above-mentioned amino acid derivates are created enzymatically, after the protein is formed. However, there are at least two known non-natural amino acids, selenocysteine and pyrrolysine, which are created beforehand and integrated into the forming protein. For more details see the Amino Acids Page.

Some non-natural amino acids


How is the mature protein formed from free amino acids? The plan for the formation of each protein is coded by a specific gene in the cell’s DNA. The cell has a complex machinery which brings together individual amino acids and attaches them to each other in a specific sequence that is dictated by the corresponding gene. The attached amino acids form a long chain, called ‘polypeptide‘. The binding is done via the formation of a peptide bond:

The order of amino acids along the polypeptide is called the ‘primary structure‘ of the protein.


The 3D fold of proteins: secondary and tertiary structure

Although each amino acid has a different side-chain with its unique chemical properties, there are some similarities. For example, certain amino acid side-chains are hydrophilic, i.e. love to be surrounded by water. Other side-chains are hydrophobic, i.e. hate to be surrounded by water. Within the polypeptide chain, hydrophilic amino acid side chains are electrostatically attracted to each other (‘same seeking same’). Similarly, side chains of hydrophobic amino acids are attracted to each other and repelled by side chains of hydrophilic amino acids. This creates a physical force that drives the linear protein chain to fold, so as to allow as many amino acids of the same type as possible to be close to each other (watch animation):

Folding of a protein (polypeptide) chain. The folding allows hydrophobic amino acids (green spheres) to huddle together within the protein core, whereas hydrophilic amino acids (pink spheres) form the water-accessible surface of the protein. Water molecules engulfing both folded and unfolded proteins are also shown.

In most intracellular (cytoplasmic) or extracellular proteins, the folding process creates a globular shape, in which hydrophobic amino acids are buried at the core, whereas most of the hydrophilic amino acids are at the surface:

Surface-hydrophilic (gray) vs. core-hydrophobic (cyan) residues in a water-soluble protein.

This partition between surface-hydrophilic and core-hydrophobic amino acids stabilizes the protein energetically; the hydrophobic amino acids at the protein core interact favorably with each other and are kept away from the bulk water surrounding the protein, whereas the hydrophilic residues at the protein surface interact favorably with the bulk water molecules:

Surface water (animated)

Dynamic interactions between bulk water molecules and protein surface residues (taken from the DEPTH Server website). Click figure to watch animation.


Proteins that reside inside cellular membranes are also globular, but their most hydrophobic amino acids are on their surface, where they can interact favorably with the hydrophobic lipids of the membrane:

Integral membrane protein. The protein chain crosses the hydrophobic core of the membrane several times. As a result, this lipid-exposed part of the protein must also be highly hydrophobic. (Taken from this Melbourne University site)

If we looked at globular proteins up close, we would see that in most of them the polypeptide chain forms local structures such as springs (alpha-helices) and extended shapes (beta-strands). These are called ‘secondary structures‘. The parts of the chain connecting secondary structures are usually disordered (loops). In water-soluble proteins the patterns of secondary structures are quite diverse (see below), whereas in membrane-bound proteins they are simpler due to the constraints applied by the surrounding lipids. 

Secondary structures of the protein main chain. Alpha-helices are in red and beta-strands are in yellow.

The overall organization of all local structures and loops in the proteins creates its folded 3D shape, called ‘tertiary structure‘.

Not all proteins are globular. Some proteins, especially those that reside in the extracellular matrix are said to be fibrous because they have an elongated shape and arranged as fibers. This includes, for example, collagen, which is the principle protein in animal connective tissues:

The fibrous structure of collagen

Fibrous proteins also contain the three levels of structure. However, their tertiary (3D) structure is usually simple and is composed of a repetitive pattern of a single secondary structure element. This level of structure is referred to as ‘super-secondary structure‘. For example, the fibrous protein alpha-keratin, which builds our hair and nails, is composed of two alpha-helical polypeptide chains. These are wound around each other in a shape called ‘coiled coil‘:

The coiled-coil structure of alpha-keratin


Cofactors & prosthetic groups

Although proteins are made of amino acids, many require additional elements for their function. These may be elemental metals (e.g. zinc, iron, copper & selenium) or small organic groups (e.g. nucleotides, monosaccharides, lipids & others). These are collectively referred to as ‘hetero-atoms/groups‘. In any case such atoms/groups carry out functions that the protein’s amino acids are either unable to do, or able to do with significantly lower efficiency.

Functions carried out by protein hetero-atoms/groups are diverse; electron/proton transfer, binding of small molecules, photo-activation, bond polarization, electrostatic stabilization and more. Some hetero-atoms/groups bind reversibly to the protein when the action needs to be carried out, while others (called ‘prosthetic groups‘) are bound to the protein at all times and constitute an integral part of its 3D structure. A famous example is the heme group of the protein hemoglobin. This group includes a pyrole-based organic structure, in the middle of which a cationic iron is embedded:

HemeThe heme group of hemoglobin (source)


Metals in proteins have many biological roles. Here are some examples:

Iron (Fe)

  • Oxygen transport – as part of hemoglobin and myoglobin. The first transports oxygen from the lungs to peripheral tissues, whereas the latter stores oxygen in muscles (mainly in ‘red’ or ‘dark’ muscles, which require a constant supply of oxygen)
  • Energy production and photosynthesis – as part of the electron transport chain.
  • Metabolism – as part of different enzymes.
  • Anti-oxidation – as part of the enzymes catalase and peroxidase.
  • Detoxification of drugs and poisons – as part of cytochrome P450.

Zinc (Zn)

  • DNA replication and transcription – as part of DNA-binding proteins.
  • Development of the skeletal and reproductive systems
  • Wound healing – as part of various extracellular matrix proteins and enzymes.
  • The immune response

Copper (Cu)

  • Energy production and photosynthesis – as part of the mitochondrial electron transport chain
  • Synthesis of various biomolecules
  • Bone mineralization
  • Anti-oxidation – as part of the enzyme superoxide dismutase

Magnesium (Mg)

  • DNA replication, repair, and stabilization
  • Energy production, biosynthesis, and photosynthesis (chlorophyll)
  • Formation of bones and teeth

Calcium (Ca)

Cellular signaling

Muscle contraction


Blood clotting – by binding to coagulation factors

Bone and teeth building – as a structural component of bones.


In enzymes, hetero-atoms/groups are called ‘cofactors‘, as they are crucial to the enzymatic function. These can be separated to the following groups:

  1. Metal ions – function in electrostatic stabilization/activation of the substrate, and/or electron transport.
  2. Small organic groups (‘coenzymes‘) – are usually derived from vitamins (see this page), and carry out diverse functions.  

CoenzymesSome common co-enzymes in central metabolism (source)


Vitamins and the co-enzymes derived from them

(source; click image to enlarge) (see also this page for further details)


The quaternary structure

Finally, many proteins tend to include more than one polypeptide chain. The different chains interact with each other non-covalently and form what is referred to as ‘quaternary structure‘.  The joining of polypeptide chains in such proteins is required for their function. A well-known example for proteins having quaternary structure is hemoglobin, the proteins which transfers oxygen from our lungs to all other tissues, thus allowing them to breath. Hemoglobin has a quaternary structure which includes four polypeptide chains:

The quaternary structure of hemoglobin. Each of the polypeptide chains comprising the overall structure is in different color, each including ‘heme’, the oxygen-binding co-factor (shown as sticks).



As mentioned above, protein function results from its ability to bind its cognate ligand, and in the case of enzymes induce catalysis. Both require the formation of a binding/active site within the proteins, in which the ligand is surrounded by chemical groups that physically interact with it and (in the case of enzymes) act chemically on it.  These functionally important chemical groups are the side chain (and to a lesser extent main chain) atoms of the protein, and their careful positioning around the ligand is a direct result of the specific 3D fold of the protein. This demonstrates a central paradigm in macro-molecules: Structure determines function.

We have seen that proteins fold due to the physical attraction between their amino acid side-chains. The specific attraction pattern depends on the unique sequence of the protein. Therefore, the unique 3D fold of the protein depends on its sequence. In other words, the information for the specific structure of proteins, which in turn determines their function, is encoded in the simple order of amino acids along the chain! This “sequence determines structure, and therefore function” realization came more than 30 years ago thanks to the famous experiment of Christian Anfinsen. In this experiment, Anfinsen disturbed the 3D structure of an isolated enzyme called Ribonuclease by using chemical agents. When those chemicals were removed, the protein regained its 3D structure and enzymatic function. This happened despite the fact that the protein was isolated in a test tube and had no help from other molecules which may reside inside its natural cellular environment. The inescapable conclusion was, therefore, that all the information for folding was already there, i.e., encoded in the protein’s sequence.



The realization that structure and function are tightly connected in proteins is the basis for a distinct field in biological sciences called “structural biology”. Structural biologists study the structures of proteins and other large molecules, in order to understand the exact factors which determine their function. The first step in studying a new protein using this approach is determining its 3D structure. This is not a simple task, and requires very expensive and complex tools, long periods of work, and a lot of patience. In some cases, the structure can be predicted (to a certain degree of accuracy) by computational methods. There are two basic computational approaches to determine structural aspects of proteins. The first tries to find resemblance between the sequence of the protein to that of proteins with known 3D structure. It relies on the “sequence determines structure” paradigm explained above. If the new protein has very similar sequence to the old one (with known structure), then it is assumed they have very similar structures. This approach is called “homology modeling“. This is a powerful tool for structure prediction, and its accuracy is increasing with the number of known 3D structures. To make it work, the sequence of the unknown protein usually has to be compared to more than one sequence protein with known structure (multiple sequence alignment). This procedure benefits from human insight, and therefore good modeling is usually done by experienced investigators. However, some automated tools for homology modeling do exist (e.g. Swiss Model).

The second computational approach is called biophysical“, since it relies on the physical-chemical properties of all amino acids building the protein chain, to calculate their interactions with each other, and (based on that) predict the folding path of the chain. The calculations involved in this approach are computationally demanding, and as a result, their in predicting folding in an accurate manner is very limited. However, with the increasing growth of computational power, the predictive power of this approach is expected to increase as well. Perhaps the biggest advantage of the biophysical approach is its reliance on basic physical principles. This endows it with two abilities. First, it is independent of data from other resources, such as sequences and structures of already known proteins. Secondly, it can be used to study other important aspects of proteins, besides predicting their structure. For example, the structure-function relationship in proteins can be studied by calculating key physical features determined by the 3D distribution of protein atoms and in turn affecting the function of the protein.



One such feature is dynamics. Although proteins ‘spend’ most of their time in their most stable conformation (called “the native state”), they constantly shift between this conformation and others, which are slightly less stable. This shifting is the result of atomic motions in the protein, and the energy it requires comes from the heat in the environment. In other words, proteins know how to convert the heat energy in their environment into kinetic energy, which manifests as atomic motions and conformational changes. The animation below shows the conformational changes in a protein, recorded by a laboratory biophysical technique called nuclear magnetic resonance spectroscopy (NMR):


(click on figure to view animation)

The motions inside proteins are diverse and range from atomic vibrations, through rotations of amino acid side chains and secondary elements, to movements of whole parts of the protein with respect to each other. For example, in the following animation of leucine binding protein, one part of the protein moves with respect to the other due to a hinge motion located in the linking region between the two parts:

hinge motion (1usg-1usi)  (created by the MovieMaker server using pdb files 1usg and 1usi)

The dynamics of a given protein 3D structure can also be predicted using different methods, such as normal mode analysis (NMA). The figure below shows the prediction of conformational changes in chicken lysozyme. Only the main chain of the protein is shown, which allows discerning its secondary structure. The animation shows that the most mobile parts of the protein are those that have the shape of loops. Alpha helices and beta strands, which are more ordered, have less mobility.

Lysozyme dynamics

Dynamics of lysozyme, predicted by the ENCoM server

Many studies have shown dynamics to be crucial to protein function. For example, the binding of one oxygen molecule to the red blood cell protein hemoglobin induces conformational changes in the protein which make it easier for additional oxygen molecules to bind. This phenomenon is called “allostery“, and it is also the mechanism on which the regulation of enzymes by small cellular metabolites is based on; binding of the metabolite induces conformational changes in the enzyme, which change its function. Interestingly, proteins maintain their dynamics even in the absence of regulating molecules, It seems that the regulators just modulate those natural dynamic changes and this way either activate or inhibit the protein. The animation below shows the interpolated shift between two experimentally-determined enzyme conformation, one is active and the second is inactive:


(click on figure to view animation).


Notice the inhibitor molecule in the upper left side of the picture. This molecule appears bound to one conformation alone (the inactive one), which matches its geometry and thus allowing it to bind. Again, the shift between the two conformations is spontaneous, but the binding of the inhibitor to the inactive conformation stabilizes it and prolongs the time which the protein spends in this conformation.



Finally, proteins can be broken down in our body to produce energy, although they normally are not used for this purpose. Indeed, our body normally derives energy from the breakdown of carbohydrates and fats. Proteins are degraded constantly as part of their normal turnover (up to 250 gram/day in the adult human body). However, they are used for the production of net energy only in the following cases:

  • During prolonged fasting.
  • In untreated cases of diabetes.
  • When the diet is rich in proteins

Proteins destined for degradation arrive both from our food and our own body tissues. Food-derived proteins are degraded in the digestive system by enzymes like pepsin, trypsin, chemotrypsin, and elastase. In contrast, proteins already present in our tissues are degraded inside the cells by two cellular system:

  1. The ubiquitine-proteasome system – a highly specific proteolytic system which is responsible for the degradation of abnormal/damaged proteins, as well as regulatory proteins which need to act only for short times. As such, this system also participates in setting the specific half-lives of the different cellular proteins.
  2. Lysosomes – these membrane-enclosed vesicles contain proteolytic enzyme that degrade proteins under acidic pH. Cellular proteins are engulfed by lysosomes in a less specific manner than the proteasome. Lysosomes are therefore responsible for the degradation of many cellular proteins. Still, their activity is regulated by hormones like insulin and glucocorticoids, as well as by by amino acids.

Whether a protein arrives from the food or from body tissues, after its breakdown the resulting amino acids are further degraded, either to yield energy or to be converted to other important metabolites (these processes are described in detail in the following section). The breakdown of amino acids releases their amino groups as ammonia, which is toxic. The ammonia must therefore be immediately integrated into a new molecule or excreted from the body via urine. Ammonia can be integrated into a nucleotide, a new amino acid, or a biological amine.

Although some of the ammonia is excreted ‘as is’ by the kidneys, most of it is first converted by the liver to a less toxic chemical, urea, which is then transferred to the kidneys for excretion via urine. The process, termed ‘urea cycle‘, occurs in the mitochondria and cytosol of liver cells, and requires aspartate as the source of the second amino group of urea

Ammonia to urea

(click to enlarge)

In some cases, ammonia may build up in the body (hyperammonemia). This happens due to:

  • Liver damage – e.g. in cirrhosis.
  • Low blood supply to the kidneys – e.g. as a result of dehydration or congestive heart failure.
  • Acute renal insufficiency.
  • Lower urinary track disease (tumor, stones).

The buildup of ammonia is dangerous; it disrupts the Krebs cycle by aminating α-ketoglutarate to glutamate, thus ‘steeling’ the important intermediate from the cycle. As a result, energy production in the brain is severely damaged, causing harsh neurological symptoms which may lead to coma (‘coma hepatica‘) or even death.

Urea may also build up in the blood (uremia), as a result of kidney damage. Indeed, a lab test of urea buildup, called ‘blood nitrogen urea’ (B.U.N), is used as a diagnostic tool for kidney failure.


The carbon skeleton left after removal of ammonia from the amino acid is a keto acid.These carbon skeletons may be further degraded for energy production via glycolysisand the citric acid cycle.  Alternatively, they may be used as a building block for different metabolites (see Figure 16 below) or biogenic amines (see section 5 above). Amino acids whose degradation forms metabolic intermediates that can be converted to glucose via gluconeogenesis are called ‘glucogenic‘. Conversely, amino acids whose degradation forms intermediates that can be converted to ketone bodies(acetoacetate, β-hydroxybutyrate or acetone) are called ‘ketogenic‘.

Amino acids conversion to metabilites

(Taken from Lehninger’s Principles of Biochemistry, 5th edition)


Genetic defects in enzymes participating in amino acid degradation pathways lead to various diseases, such as Maple Syrup Disease and Phenylketonuria (PKU). In the latter, a defect in the enzyme phenylalanine hydroxylase prevents the conversion of phenylalanine to tyrosine. The accumulation of the former inhibits the transfer of other amino acids into the brain, which impairs the synthesis of proteins and myelin. This results in severe mental and developmental retardation in infants, as well as to shorter life expectancy. Thus, to avoid these severe outcomes, individuals with PKU must keep a low-protein diet and avoid drinking soda beverages which contain aspartam (has phenylalanine in its structure).


You can learn more about proteins structure & function in the following online courses:


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