Proteins

Protein Metabolism
Proteins make up the structural tissue for muscles and tendons, transport oxygen or hemoglobin, catalyze all biochemical reactions as enzymes, and regulate reactions as hormones. Our bodies must be able to synthesize the many proteins, amino acids, and other non-protein nitrogen containing compounds needed for growth, replacement, and repair. Proteins in excess are used to supply energy or build reserves of glucose, glycogen, or lipids.

Digestion of Proteins
k Mouth-No digestion occurs k Stomach-Protein digestion starts

Gastrin-stimulates parietal cells to secrete HCl: chief cells of the gastric glands to secretepepsinogen. Hydrochcloric acid- denatures protein structure -activates pepsinogen(zymogento pepsin) Pepsin (gastric protease)- hydrolyzes proteins to smaller polypeptides and some free aminoacid Pepsincuts protein into peptides in the stomach k Small Intestine- peptidases enzyme Secretin- stimulates the pancreas to secrete bicarbonate into the small intestine to neutralize the gastricHCl

Cholecystokinin- stimulates secretion of several pacreatic enzyme with activity optima ph 7-8. Trypsin(pancreatic protease) and chymotrypsincut proteins and larger peptides into smaller peptides in the small intestine Aminopeptidaseand carboxypeptidasesA and B degrade peptides into amino acids in the small intestine k Proteins arebreak down into: Tripeptides Dipeptides Free amino acids

Absorption of Amino acid

kWhole proteins are not absorbed. Too large to pass

through the cell membranes intact. k Hydrolases(digestive enzymes)- break peptide bonds Free amino acid small intestine (villi) Liver blood circulation

Deaminationof Proteins
-the bodily process in which amino groups are removed from excess proteins allows - the system to convert excess amino acids into usable resources such as hydrogen and carbon k The process also plays a vital role in removing nitrogen waste from the body. k Amino groups discarded as a result of the process are converted into ammonia, which is later expelled from the body through urination.

kLiver- chief cite of deamination in the human body.

Hydrolytic enzymes found in the organ separate the NH2 amino groups from proteins. The process leaves behind a carbon skeleton composed primarily of hydrogen, carbon, and oxygen. This skeleton can later be converted into usable glucose and lipids, indirectly making deamination one of the body's energyproducing mechanisms.

The Process of deamination

k Amino groups removed via deamination bond with a hydrogen molecule to form ammonia. Ammonia, however, is toxic to the human body and must be discarded. A separate chemical process combines the resulting ammonia with carbon dioxide, converting it into either urea or uric acid. Both compounds are diffused into the blood and later filtered out through the kidneys. The urea and uric acid are then expelled from the body via urination.

The Process Of The process was at first thought to be one of Deamination simple hydrolysis
k R-CHNH2-COOH + HOH = R-CHOH-COOH +

NH3 -Otto Neubauer, who first showed that the process of deamination- might be one oxidation and not, hydrolysis. k R-CHNH2- COOH + O = R-CO-COOH + NH3 this method of oxidation is actually possible in the organism

k Deamination is also an oxidative reaction that occurs under aerobic conditions in all tissues but especially the liver. During oxidative deamination, an amino acid is converted into the corresponding keto acid by the removal of the amine functional group as ammonia and the amine functional group is replaced by the ketone group. The ammonia eventually goes into the urea cycle.

Nitrogen or Amino Acid pool

kmixture of amino acids available in the cell derived

from dietary sources or the degradation of protein. Since proteins and amino acids are not stored in the body, there is a constant turnover of protein. Some protein is constantly being synthesized while other protein is being degraded.

Synthesis of New Amino Acids

k these reactions can also be used to synthesize

amino acids needed or not present in the diet. An amino acid may be synthesized if there is an available "root" ketoacid with a synthetic connection to the final amino acid. Since an appropriate "root" keto acid does not exist for eight amino acids, (lys, leu, ile, met, thr, try, val, phe), they are essential and must be included in the diet because they cannot be synthesized

k if there are excess proteins in the diet those amino acids converted into pyruvic acid and acetyl CoA can be converted into lipids by the lipogenesis process. If carbohydrates are lacking in the diet or if glucose cannot get into the cells (as in diabetes), then those amino acids converted into pyruvic and oxaloacetic acids can be converted into acid glucose or glycogen. k The hormones cortisone and cortisol from the adrenal cortex stimulate the synthesis of glucose from amino acids in the liver and also function as antagonists to insulin.

B}d[ eieuev iv au}v of protein:

k ADULT MEN :minimum 56 grams per day or 0.8 grams of protein /kg of boy weight ,or double 1.6 grams /kg if athletically active and building muscle k ADULT WOMEN: minimum 46 grams /day or 0.8 grams of protein /kg of body weight, or double to 1.6 grams/kg if active and building muscle athletically

Metabolic pathways
k series of chemical reactions occurring within a

cell. k A metabolic pathway involves the step-by-step modification of an initial molecule to form another product. The resulting product can be used in one of three ways: k To be used immediately, k To initiate another metabolic pathway, called a flux generating step k To be stored by the cell

k products of one reaction are the substrates for the subsequent reactions k Metabolic pathways are often considered to flow in one direction Glycolysis- was the first metabolic pathway discovered. Inktimes of excess protein energy sources, certain reactions in the glycolysis pathway may run in reverse in order to produce glucose 6-phosphate which is then used for storage as glycogen or starch.

kMetabolic pathways are often regulated by feedback inhibition k metabolic pathways flow in a 'cycle' wherein each Some component of the cycle is a substrate for the subsequent reaction in the cycle. k Anabolic and catabolic pathways in eukaryotes often occur independently of each other, separated either physically by compartmentalization within organelles or separated biochemically by the requirement of different enzymes and co-factors.

Structure

OXIDATION OF AMINO ACID

k oxidationof free aminoacidsand amino acid

residues of proteinsare derivedfrom radiolysis studies. k most common pathway for the oxidation of simple aliphatic amino acidsinvolvesthe hydroxyl radicalmediated abstraction of a hydrogenatom to form a carbon-centeredradical at the alpha-position of the amino acid or amino acid residuein the polypeptide chain.

k Addition of O2 to the carbon-centered radicals

leads to formation of proxy radical derivatives, k upon decomposition lead to production of NH3 and alpha-ketoacidosis, or to production of NH3, CO2, and aldehydes or carboxylic acids containing one less carbon atom. k the number of carbon atoms in the amino acid As is increased, hydrogen abstraction at other positions in the carbon chain becomes more important and leads either to the formation of hydroxyl derivatives

k All amino acid residues in proteins are subject to attack by hydroxyl radicals generated by ionizing radiation; however, the aromatic amino acids and sulfurcontaining aminoacids are most sensitive to oxidation

Amino acids undergo oxidative catabolism under three circumstances:

k Protein amino-acidresidues from normal turnover are

recycledto generate energy andmolecular components DLHWDU\ DPLQR DFLGV WKDW H[FHHG ERG\V SURWHLQ k synthesis needs are degraded k Proteins in the body are broken down to supply amino acids for catabolism whencarbohydrates are inshort supply (starvation, diabetes mellitus),

UREA CYCLE

Oxidative phosphorylation or OXPHOS

-is the metabolic pathway in whichthe mitochondria in cells use their structure, enzymes, and energy released by the oxidationof nutrients to reform ATP. -during oxidativephosphorylation, electrons are transferredfrom electron donors to electron acceptors such as oxygen, in redoxreactions. -is a vital part of metabolism, it producesreactive oxygenspeciessuchas superoxide and hydrogen peroxide, whichlead to propagation of freeradicals, damaging cells and contributing to disease and, possibly, aging (senescence).

k oxidative phosphorylation is a vital part of

metabolism, it produces reactive oxygen species such as superoxide and hydrogen peroxide, which lead to propagation of free radicals, damaging cells and contributing to disease and, possibly, aging (senescence).

or interruption in the processingof proteins in the body.

Protein metabolism disorder - condition in which there is a deviation

Examples of protein metabolism disorders include:

1. Phenylketonuria

--oftenreferred to as PKU, is oneof the most common protein metabolism disorders. -their bodies have excessamounts of phenylalanine andlow tyrosine levels.

untreated PKU: Lethargy Light pigment Eczema Intellectualdisability Seizures Hyperactivity

2. Tyrosinemia
- occurs whenan enzyme, called fumarylacetoacetase(FAH), is either missing or not workingproperly. - When FAH is not working, it cannot break down tyrosine.
Can Cause:serious liver and kidney damage

weakness or pain vomitingand diarrhea

3.Homocystinoria
- is an inherited disorder in which the body is unable toprocess certainbuilding blocks of proteins (aminoacids) properly. characterized by: nearsightedness(myopia), dislocation of the lens at the front of the eye,an increased risk of abnormalblood clotting, and brittle bones that are proneto fracture(osteoporosis)

k Untreated Homocystinuriamay cause intellectual disability, failure to grow and gain weight at theexpectedrate, problems with movement,blood disorder called megaloblasticanemia. k Megaloblastic anemia- occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).

4. Maple Syrup Urine Disease

-is an inherited disorder in which the body isunable to process certain protein building blocks (amino acids) properly. k Thecondition gets itsname from the distinctive sweet odorof affected infants' urine.
k A baby has the disorder may appearnormal at birth. But

within three to four days, the symptoms appear. Thesemay include: lossof appetite, fussiness,andsweet-smelling urine. The elevated levelsof amino acids in the urine generate the smell, which is reminiscent of maplesyrup. This ishow MSUD got its name. If untreated, maple syrup urine disease can lead to seizures, coma, and death.

Treatment: - involved dietary restriction of the amino acids leucine, isoleucine, and valine. This treatment mustbegin veryearlyto prevent brain damage. Babieswith the disease must eat a special formula that does not contain the amino acids leucine, isoleucine, andvaline. As the person grows to adulthood,he or shemustalways watch their diet, avoiding high protein foods such as meat, eggs, and nuts. -If levelsof the three aminoacids stillgettoo high, patients can be treated with an intravenous (given through a vein) solution that helpsthe body use up excess leucine, isoleucine, andvalinefor protein synthesis.

-Genetherapyis alsoa potential future treatment for patientswith MSUD. This would involve replacing the mutated genewith a good copy, allowingthe patient's cellsto generate a functional BCKDprotein complex and break down the excessamino acids.