In molecular biology, protein catabolism is the breakdown of proteins into smaller peptides and ultimately into amino acids. Protein catabolism is a key function of digestion process. Protein catabolism often begins with pepsin, which converts proteins into polypeptides. These polypeptides are then further degraded. In humans, the pancreatic proteases include trypsin, chymotrypsin, and other enzymes. In the intestine, the small peptides are broken down into amino acids that can be absorbed into the bloodstream. These absorbed amino acids can then undergo amino acid catabolism, where they are utilized as an energy source or as precursors to new proteins. [1]
The amino acids produced by catabolism may be directly recycled to form new proteins, converted into different amino acids, or can undergo amino acid catabolism to be converted to other compounds via the Krebs cycle. [2]
Protein catabolism produces amino acids that are used to form other proteins or oxidized to meet the energy needs of the cell. The amino acids that are produced by protein catabolism can then be further catabolized in amino acid catabolism. Among the several degradative processes for amino acids are Deamination (removal of an amino group), transamination (transfer of amino group), decarboxylation (removal of carboxyl group), and dehydrogenation (removal of hydrogen). Degradation of amino acids can function as part of a salvage pathway, whereby parts of degraded amino acids are used to create new amino acids, or as part of a metabolic pathway whereby the amino acid is broken down to release or recapture chemical energy. For example, the chemical energy that is released by oxidization in a dehydrogenation reaction can be used to reduce NAD+ to NADH, which can then be fed directly into the Krebs/Citric Acid (TCA) Cycle. [2]
Protein degradation differs from protein catabolism. Proteins are produced and destroyed routinely as part of the normal operations of the cell. Transcription factors, proteins that help regulate protein synthesis, are targets of such degradations. Their degradation is not a significant contributor to the energy needs of the cell. [3] The addition of ubiquitin (ubiquitylation) marks a protein for degradation via the proteasome. [4]
Oxidative deamination is the first step to breaking down the amino acids so that they can be converted to sugars. The process begins by removing the amino group of the amino acids. The amino group becomes ammonium as it is lost and later undergoes the urea cycle to become urea, in the liver. It is then released into the blood stream, where it is transferred to the kidneys, which will secrete the urea as urine. [5] [6] The remaining portion of the amino acid becomes oxidized, resulting in an α-keto acid. The alpha-keto acid will then proceed into the TCA cycle, in order to produce energy. The acid can also enter glycolysis, where it will be eventually converted into pyruvate. The pyruvate is then converted into acetyl-CoA so that it can enter the TCA cycle and convert the original pyruvate molecules into ATP, or usable energy for the organism. [7]
Transamination leads to the same result as deamination: the remaining acid will undergo either glycolysis or the TCA cycle to produce energy that the organism's body will use for various purposes. This process transfers the amino group instead of losing the amino group to be converted into ammonium. The amino group is transferred to α-ketoglutarate, so that it can be converted to glutamate. Then glutamate transfers the amino group to oxaloacetate. This transfer is so that the oxaloacetate can be converted to aspartate or other amino acids. Eventually, this product will also proceed into oxidative deamination to once again produce alpha-ketoglutarate, an alpha-keto acid that will undergo the TCA cycle, and ammonium, which will eventually undergo the urea cycle. [8]
Transaminases are enzymes that help catalyze the reactions that take place in transamination. They help catalyze the reaction at the point when the amino group is transferred from the original amino acid, like glutamate to α-ketoglutarate, and hold onto it to transfer it to another α-ketoacid. [8]
Some key factors that determine overall rate include protein half-life, pH, and temperature.
Protein half-life helps determine the overall rate as this designates the first step in protein catabolism. Depending on whether this step is short or long will influence the rest of the metabolic process. One key component in determining the protein half-life is based on the N-end rule. This states that the amino acid present at the N-terminus of a protein helps determine the protein's half-life. [9]
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, and metabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost all areas of the life sciences are being uncovered and developed through biochemical methodology and research. Biochemistry focuses on understanding the chemical basis which allows biological molecules to give rise to the processes that occur within living cells and between cells, in turn relating greatly to the understanding of tissues and organs as well as organism structure and function. Biochemistry is closely related to molecular biology, the study of the molecular mechanisms of biological phenomena.
The citric acid cycle—also known as the Krebs cycle, Szent-Györgyi-Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.
α-Ketoglutaric acid is a keto acid.
The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic.
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently, its IUPAC systematic name is 2-aminopropanoic acid, and it is classified as a nonpolar, aliphatic α-amino acid. Under biological conditions, it exists in its zwitterionic form with its amine group protonated (as −NH3+) and its carboxyl group deprotonated (as −CO2−). It is non-essential to humans as it can be synthesised metabolically and does not need to be present in the diet. It is encoded by all codons starting with GC (GCU, GCC, GCA, and GCG).
Glutamic acid is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABAergic neurons.
Pyruvic acid (IUPAC name: 2-oxopropanoic acid, also called acetoic acid) (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Cellular respiration is the process by which biological fuels are oxidized in the presence of an inorganic electron acceptor, such as oxygen, to drive the bulk production of adenosine triphosphate (ATP), which contains energy. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into ATP, and then release waste products.
The term amphibolic is used to describe a biochemical pathway that involves both catabolism and anabolism. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into amino acids, or a triglyceride into fatty acids, or a disaccharide into monosaccharides are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy.
Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential amino acids to non-essential amino acids.
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle.
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.
Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.
The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
Oxidative deamination is a form of deamination that generates α-keto acids and other oxidized products from amine-containing compounds, and occurs primarily in the liver. Oxidative deamination is stereospecific, meaning it contains different stereoisomers as reactants and products; this process is either catalyzed by L or D- amino acid oxidase and L-amino acid oxidase is present only in the liver and kidney. Oxidative deamination is an important step in the catabolism of amino acids, generating a more metabolizable form of the amino acid, and also generating ammonia as a toxic byproduct. The ammonia generated in this process can then be neutralized into urea via the urea cycle.
A glucogenic amino acid is an amino acid that can be converted into glucose through gluconeogenesis. This is in contrast to the ketogenic amino acids, which are converted into ketone bodies.
In organic chemistry, keto acids or ketoacids are organic compounds that contain a carboxylic acid group and a ketone group. In several cases, the keto group is hydrated. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis.
The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.
In molecular biology, the ELFV dehydrogenase family of enzymes include glutamate, leucine, phenylalanine and valine dehydrogenases. These enzymes are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.