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utritional Biochemistry. İlker GÖÇHAN (M.D) Clinical Biochemistry Specialist. Protein metabolism. WEEK 13. Protein Metabolism.
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utritionalBiochemistry İlker GÖÇHAN (M.D) Clinical Biochemistry Specialist
Protein metabolism WEEK 13
Protein Metabolism • Protein metabolism is an essential part of metabolism. Sinceamino-acid metabolism is closely connected with themetabolism of other nitrogen compounds, protein metabolismis often included in the more general concept of nitrogen metabolism. • In autotrophic organisms—that is, plants (except • fungi) and chemo-synthesizing bacteria—protein metabolism begins with the assimilation of inorganic nitrogen andsynthesis of amino acids and amides.
In man and animals, only a portion of the amino acids—the so-called nonessentialones—can be synthesized in the organism from simpler organic compounds. • The other portion—the essential aminoacids—must be obtained from food, usually as protein.
Proteins contained in various foods are broken down bycleavage under the action of such proteolytic enzymes aspepsin, trypsin, and chymotrypsin into amino acids, which areabsorbed into the blood and carried to organs and tissues.
A considerable portion of amino acids are used in theformation and completion of various proteins in thebody, including functionally active proteins (enzymes,hormones, antibodies, and so forth), plastic proteins, structural proteins, and others.
At the same time, thebody’s proteins undergo constant breakdown andrenewal, replenishing the reserve of free amino acids. • The other portion of the amino acids is used in theformation of a number of low-molecular hormones,biologically active peptides, amines, pigments, andother substances necessary for the maintenance oflife.
For example, the amino acid glycine is used to • form purine bases, and aspartic acid is used to • synthesize pyrimidine bases.
The mutual transformation of amino acids is, insignificant measure, produced by a process that iswidespread in all organisms—the enzyme process,involving the transfer of amino groups. • This process, called transamination, was discovered bythe Soviet scientists A. E. Braunshtein and M. G.Kritsman. Excess amino acids undergo enzyme processes of decomposition.
The most common initial reaction of amino-aciddecomposition is deamination, primarily oxidativedeamination, after which the nitrogen-freeremainder of the amino-acid molecule degrades tothe end products—carbon dioxide, water, andnitrogen that splits off in the form of ammonia.
The transformation and fate of food proteinsfrom their ingestion to the elimination of their excretion products: • Proteins are of exceptional importance toorganisms because they are the chiefconstituents, aside from water, of all the softtissue of the body.
Special proteins haveunique roles as structural and functionalelements of cells and tissues. • Examples arekeratin of skin, collagen of tendons, actin andmyosin of muscle, the blood proteins, enzymesin all tissues, and protein hormones of the hypophysis.
Protein is digested to amino acids in thegastrointestinal tract. • These are absorbed anddistributed among the different tissues, wherethey form a series of amino acid pools that arekept equilibrated with each other through themedium of the circulating blood. • The needs forprotein synthesis of the different organs are supplied from these pools.
Excess amino acids in the tissue pools lose their nitrogen by a combination of transamination and deamination. • The nitrogen is largely convertedto urea and excreted in the urine. The residualcarbon products are then further metabolizedby pathways common to the other major foodstuffs—carbohydrates and fats.
Protein digestion occurs to a limited extent inthe stomach and is completed in theduodenum of the small intestine. • The main proteolytic enzyme of the stomach is pepsin,which is secreted in an inactive form, pepsinogen.
Its transformation to the activepepsin, initiated by the acidity of the gastricjuice, involves liberation of a portion of thepepsinogen molecule as a peptide. • Pepsin preferentially hydrolyzes peptide bonds containing an aromatic amino acid, and itrequires an acid medium to function.
The acid chyme is discharged from the stomach, containing partially degraded proteins, into a slightly alkaline fluid in the small intestine. • This fluid is composed ofpancreatic juice and succus entericus, the intestinal secretion.
The pancreas secretes three known proteinases, trypsin, chymotrypsin, and carboxypeptidase. • All three are secreted as inactive zymogens. Activationstarts with the transformation of the inactivetrypsinogen into the active trypsin. Trypsin, in turn, activates chymotrypsin and carboxypeptidase.
Trypsin and chymotrypsin are endopeptidases;that is, they cleave internal peptide bonds. • The so-called peptidases are exopeptidases; they • cleave terminal peptide bonds. • Trypsin has a predilection for those containing the basicamino acid residues of lysine and arginine.
These two proteinases perform the major sharein hydrolyzing proteins to small peptides.Digestion to amino acids is completed by the exopeptidases. • Carboxypeptidase acts on peptides from the free carboxyl end;aminopeptidases from the free amino end. • Other peptidases act on di- or tripeptides, orpeptides containing such special amino acids as proline.
The amino acid digestion products of theproteins are absorbed by the smallintestine as rapidly as they are liberated. • The absorbed amino acids are carried bythe portal blood system to the liver, fromwhich they are distributed to the rest of the body.
Small amounts of the peptidesformed during digestion escape furtherhydrolysis and may also enter thecirculation from the intestine. This isshown by a rise in the peptide nitrogen in the blood.
PROTEIN IS • A major component of foods. It is digestedfirstly in the stomach, and then in the duodenum to dipeptides and amino acid. • Absorbed using symport active transport with sodium. • Stored in liver and muscles.
Uses • Protein synthesis : The synthesis of newproteins is very important during growth. Inadults new protein synthesis is directedtowards replacement of proteins as they are constantly turned over. • Synthesis of a variety of other compounds :Examples of compounds synthesized fromamino acids include purines and pyrimidines (components of nucleotides), catecholamines (adrenaline and noradrenalin) & • neurotransmitters (serotonin)
Amino acidcatabolism • The other biological fuels discussed (carbohydrates & fats) contain only theelements carbon, hydrogen and oxygen. • Amino acids contain nitrogen as well. Thefirst step in amino acid catabolism is theremoval of the nitrogen (the amino group).
Nitrogen removal from amino acids Aminotransferase PLP
Transamination • it is a process of transferring amino groups from one • molecule to another. • There is no formation and noexceretion of ammonia, thusly no net change in the nitrogen amount of body.
It is a process involved in aminoacids in which the amino group is transferred from theamino acid to a certain α-ketoacid with the consequantformation of a second α-ketoacid and amino acid. • The reaction is catalyzed by the enzyme aminotranferase (akatransaminase) which requires pyridoxal phosphate as a prosthetic group.
All transaminases contain this prostheticgroup which derives from pyridoxine a water solublevitamin also known as vitamin B6. • The amino group from amino acids is temporarily uptaken by the pyridoxalphosphate as pyridoxamine phosphate prior to its donationto an α-ketoacid. All aminoacids except lysine, threonine, proline and hydroxyproline participate in transamination process.
Deamination • it is a process of removing amino groups from onemolecule in order to reduce the amount of nitrogen of thebody through ammonia synthesis and elimination. • It is a process occurring in the liver during the metabolism of amino acids. • The amino group is removed from the aminoacid and converted to ammonia-NH3 whose toxic activity iscanceled by conversion into urea which is eventually excreted.
The glutamate dehydrogenase-GDH enzyme occupies a central role in nitrogen metabolism. • Glutamate amino acid is cleaved into α-ketoglutarate and ammonia areaction catalyzed by GDH in a process called deamination.
Glutamate is the only amino acid thatundergoes oxidative deamination at a relatively high rate. • The formation of ammonia from the amino group thuslyoccurs mainly via the amino group of glutamate.
Once the amino groups have all been "collected“in the form of the one amino acid, glutamate, thisamino acid has its amino group removed (termed"oxidative deamination"). • This reaction reformsalpha-ketoglutarate with the other product beingammonia (NH4 +).
Ammonia is toxic to the nervous system and itsaccumulation rapidly causes death. Therefore itmust be detoxified to a form which can be readilyremoved from the body. • Ammonia is converted tourea, which is water soluble and is readilyexcreted via the kidneys in urine.
Unlike glucose, there is nostorage form of amino acids. • Amino acids are degraded intofree ammonia (NH4+) and the carbon skeleton. • Living organisms excrete excess nitrogen as ammonia, uric acid, and urea.
Excretoryforms of nitrogen • Excess NH4 + is excreted as ammonia (microbes,aquatic vertebrates or larvae of amphibia), • b) Urea (many terrestrial vertebrates) • c) or uric acid (birds and terrestrial reptiles)
Nitrogen removal from amino acids • Step 1: Remove amino group • Step 2: Take amino group to liver for nitrogen excretion • Step 3: Entry into mitochondria • Step 4: Prepare nitrogen to enter urea cycle • Step 5: Urea cycle
The urea cycle takes place in the mitochondria and the cytosol. There are four enzymes involved, three of which are cytosolic and one is mitochondrial.
Sources • Lippincott’s Illustrated Reviews: Biochemistry, 3rd edition.
