De Amination

7/27/2019 De Amination

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Protein Metabolism

Proteins make up the structural tissue for muscles andtendons, transport oxygen or hemoglobin, catalyze all

biochemical reactions as enzymes, and regulate reactions

as hormones. Our bodies must be able to synthesize themany proteins, amino acids, and other non-proteinnitrogen containing compounds needed for growth,replacement, and repair. Proteins in excess are used to

supply energy or build reserves of glucose, glycogen, orlipids.



Digestion of Proteinsk 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 stomachk 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 acidkWhole 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 areremoved from excess proteins

-allows the system to convert excess amino acidsinto usable resources such as hydrogen andcarbon

k The process also plays a vital role in removing

nitrogen waste from the body.kAmino groups discarded as a result of the processare converted into ammonia, which is laterexpelled 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 processleaves behind a carbon skeleton composed primarilyof hydrogen, carbon, and oxygen. This skeleton can laterbe converted into usable glucose and lipids, indirectly

making deamination one of the body's energy-producing mechanisms.



The Process of deaminationkAmino 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 theresulting ammonia with carbon dioxide, converting it

into either urea or uric acid. Both compounds arediffused into the blood and later filtered out through

the kidneys. The urea and uric acid are then expelledfrom the body via urination.





kDeamination is also an oxidative reaction that occursunder aerobic conditions in all tissues but especiallythe liver. During oxidative deamination, an amino

acid is converted into the corresponding keto acid bythe removal of the amine functional group as ammonia

and the amine functional group is replaced by theketone group. The ammonia eventually goes into the

urea cycle.



Nitrogen or Amino Acid poolkmixture of amino acids available in the cell derivedfrom dietary sources or the degradation of protein.

Since proteins and amino acids are not stored in thebody, there is a constant turnover of protein. Someprotein is constantly being synthesized while otherprotein is being degraded.





Synthesis of New Amino Acidsk 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 anavailable "root" ketoacid with a syntheticconnection to the final amino acid. Since anappropriate "root" keto acid does not exist for

eightamino acids, (lys, leu, ile, met, thr, try, val, phe),they are essential and must be included in the diet

because they cannot be synthesized



kif there are excess proteins in the diet those amino

acids converted into pyruvic acid and acetyl CoAcan be converted into lipids by the lipogenesisprocess. If carbohydrates are lacking in the diet or

if glucose cannot get into the cells (as in diabetes),

then those amino acids converted into pyruvicacidand oxaloacetic acids can be converted intoglucose or glycogen.

k The hormones cortisone and cortisol from the

adrenal cortex stimulate the synthesis of glucosefrom amino acids in the liver and also function asantagonists to insulin.



B}dÇ[ Œe‹µiŒeuevš iv

au}µvš of protein:kADULT 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

kADULT WOMEN: minimum 46 grams /day or 0.8 gramsof protein /kg of body weight, or double to 1.6

grams/kg if athletically active and building muscle



Metabolic pathwaysk series of chemical reactions occurring within a

cell.

k A metabolic pathway involves the step-by-stepmodification of an initial molecule to formanother product. The resulting product can beused in one of three ways:

k To be used immediately,

k To initiate another metabolic pathway, called aflux generating step

k To be stored by the cell



kthe products of one reaction are the substrates forsubsequent reactions

kMetabolic pathways are often considered to flow inone direction

Glycolysis- was the first metabolic pathwaydiscovered.

kIn times of excess protein energy sources, certainreactions in the glycolysis pathway may run in

reverse in order to produce glucose 6-phosphatewhich is then used for storage as glycogen orstarch.



kMetabolic pathways are often regulated by feedbackinhibition

kSome metabolic pathways flow in a 'cycle' wherein eachcomponent of the cycle is a substrate for the subsequent

reaction in the cycle.

kAnabolic and catabolic pathways in eukaryotes oftenoccur independently of each other, separated either

physically by compartmentalization within organelles orseparated biochemically by the requirement of different

enzymes and co-factors.



Structure



OXIDATION OF AMINO ACIDk oxidationof free aminoacidsand amino acid

residues of proteinsare derivedfrom radiolysis

studies.

k most common pathway for the oxidation of simple

aliphatic amino acidsinvolvesthe hydroxyl radical-

mediated 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 radicalsleads to formation of proxy radical derivatives,

k upon decomposition lead to production of NH3and alpha-ketoacidosis, or to production of NH3,

CO2, and aldehydes or carboxylic acids containingone less carbon atom.

kAs the number of carbon atoms in the amino acidis increased, hydrogen abstraction at otherpositions in the carbon chain becomes moreimportant 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 sulfur-

containing aminoacids are most sensitive

to oxidation



Amino acids undergo oxidative catabolism under

three circumstances:

k Protein amino-acidresidues from normal turnover arerecycledto generate energy andmolecular

components

kDLHWDU\ DPLQR DFLGV WKDW H[FHHG ERG\¶V SURWHLQ

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 energyreleased by the oxidationof nutrients to reform ATP.

-during oxidativephosphorylation, electrons aretransferredfrom electron donors to electronacceptors such as oxygen, in redoxreactions.

-is a vital part of metabolism, it producesreactive

oxygenspeciessuchas superoxide and hydrogenperoxide, whichlead to propagation of freeradicals,damaging cells and contributing to disease and,possibly, aging (senescence).







Protein metabolismdisorder- condition in which there is a deviation

or interruption in the processingof proteins

in the body.



Examples of protein

metabolismdisorders include:

1. Phenylketonuria

--oftenreferred to as PKU, is oneof themost 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 damageweakness 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 riskof 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.

kMegaloblastic 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).





Treatment:

- involved dietary restriction of the amino acids leucine,

isoleucine, and valine. This treatment mustbegin veryearlyto

prevent brain damage. Babieswith the disease must eat aspecial 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 breakdown the excessamino acids.

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