Proteins: Degradation, Urea Cycle, Amino Acid Biosynthesis and Conversion to Biologically Important Molecules

matches

in normal adults, nitrogen intake _______________ nitrogen excreted

positive nitrogen balance

excess of ingested nitrogen over excreted nitrogen; accompanies growth and pregnancy

negative nitrogen balance

output of nitrogen exceeds intake; may follow surgery, advanced cancer, and some nutritional disorders

ammonia

highly toxic compound; arises in humans primarily from the alpha-amino nitrogen of amino acids

glutamine

tissues convert ammonia to the amide nitrogen of the nontoxic amino acid _________________________

urea

subsequent deamination of glutamine in the liver releases ammonia, which is converted to _______________, which is not toxic

liver

if ____________ function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms

turnover

the continuous degredation and synthesis of cellular proteins that occurs in all forms of life

1-2

humans turn over __________% per day of their total body protein, principally muscle protein

structural rearrangement

high rates of protein degredation occur in tissues that are undergoing ______________ ________________, for example, uterine tissue during pregnancy and skeletal muscle during starvation

75

approximately ______% of the amino acids liberated by protein degredation are reutilized

degreaded

the remaining excess of free amino acids liberated by protein degredation are not stored for future use and are rapidly _______________

amphibolic, urea

in humans, the major portion of the carbon skeletons of the amino acids is converted to ________________ intermediates, while the amino nitrogen is converted to _____________ and excreted in urine

stomach

protein digestion begins in the ____________ and consists of two steps:

1) denaturation by effect of very low pH (1-2)

2) degredation by the proteolytic enzyme pepsin

pepsin

proteolytic enzyme that degrades proteins in the stomach

oligopeptides

stomach digestion of proteins results in a mixture rich in ____________________

small intestin

where digestion of oligopeptides occurs by pancreatic peptidases that further breakdown to di- and tripeptides as well as amino acids

secretin

stimulates the pancreatic secretion of HCO3- to restore normal pH in the small intestine

cholecystokinin

stimulates the secretion of pancreatic peptidases that break oligopeptides into di- and tripeptides, as well as amino acids

intestinal

full degredation of amino acids is completed inside the _______________ cells

blood

amino acid leave intestinal cells and are transported by _____________ to different tissues to be transformed to other molecules or to build new proteins

housekeeping

typical _____________ enzymes such as those for glycolysis have half lives (t 1/2) values of over 100 hours

regulatory

key __________________ enzymes may have half lives (t 1/2) values as low as 0.5 to 2 hours

PEST sequences

regions rich in proline, glutamine, serine, and threonine in enzymes that act as signal peptides for intracellular degredation

endopeptidases

enzyme that hydrolyzes internal peptide bonds, degrading peptides into amino acids

aminopeptidases

enzyme that removes amino acid sequentially from the amino end

carboxypeptidases

enzyme that removes amino acids sequentially from the carboxy end

lysozomes

extracellular, membrane-associated, and long-lived intracellular proteins are degraded in _______________ by ATP-independent proteases

proteasome

degredation of regulatory proteins with short half-lives and of abnormal or misfolded proteins occurs in the cytosol and requires ATP, ubiquitin protein, and _______________________ as part of the UPP

muscle

generates over half of the total body pool of free amino acids; they are transported to different organs for processing (ex: the glucose-alanine cycle)

feeding

there is an amino acid exchange between organs and tissues immediately after _______________ to maintain steady-state concentrations, even between meals

liver

the site of the urea cycle enzymes necessary for disposal of excess nitrogen

ureotelic

humans excrete excess nitrogen as urea

ammonotelic

fish excrete excess nitrogen as ammonia

uricotelic

birds excrete excess nitrogen as uric acid

nitrogen removal

the first step in the degredation of amino acids

aminotransferases (transaminases)

catalyse the transfer of an alpha-amino group from an amino acid to an alpha-ketoacid (ex: alpha-ketoglutarate)

oxaloacetate

aspartate aminotransferase converts aspartate and alpha-ketoglutarate into ________________ and glutamate

glutamate

what alpha-ketoglutarate gets converted into after an aminotransferase reaction

pyruvate

alanine aminotransferase converts alanine and alpha-ketoglutarate into ___________ and glutamate

glutamate

transfers and releases amino groups by two mechanisms:

1) release of transferred amine from the aminotransferase reaction as free ammonium ion

2)accepting an ammonium ion on its carboxylate residue and transporting it as glutamine which can later be converted back to glutamate

oxidative deamination

reaction in which the transferred amine on glutamate gets released as a free ammonium ion and produces alpha-ketoglutarate

glutamine synthase

enzyme that allows glutamate to accept a free ammonium ion on its carboxylate residue, allowing for transport to other tissues

glutaminase

enzyme that converts glutamine back into glutamate, releasing the free ammonium ion

serine and threonine

amino acids that can be directly daminate to release ammonium ions by their respective dehydratase enzymes

carbamoyl phosphate

once in the liver, ammonium is released and converted into _______________ to begin the urea cycle in the mitochondria (three steps)

carbamoyl phosphate synthetase

major regulatory enzyme of the urea cycle

ornithine transcarbamoylase

enzyme that converts ornithine into citrulline with the addition of carbamoyl phosphate; occurs in the mitochondrial matrix

argininosuccinate synthetase

enzyme that uses ATP to convert citrulline into arginino succinate with the addition of aspartate

argininosuccinase

enzyme that releases fumarate from argininosuccinate, producing arginine

arginase

enzyme that produces urea through the hydrolysis of arginine, forming ornithine and restarting the urea cycle

cytosol

most of the urea cycle--except for the formation of citrulline--occurs in the _______________

reactants

Urea cycle _____________:

CO2

NH4+

3ATP

aspartate

2H2O

3

number of ATP molecules required for one cycle of the urea cycle

products

Urea cycle __________:

urea

2 ADP + 2 Pi

AMP + PPi

fumarate

10

an adult human excretes ___________ kg of urea/year in urine

hyperammonemia

defective enzymes or a cirrhotic liver cannot convert ammonia to urea, causing high blood levels of ammonia

nervous system

ammonia is toxic to the _____________________ and can cause coma and death

25

cirrhosis of the liver arises in the _______% of alcoholics

75

about _____% of all cases of liver cirrhosis are the result of alcoholism

viral hepatitis

a nonalcoholic cause of liver cirrhosis

amino acids

once deaminated, the carbon skeletons of the 20 fundamental ____________________ are funnelled into only 7 molecules: pyruvate, acetyl CoA, acetoacetyl CoA, alpha-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate

ketogenic

______________ amino acids can contribute to synthesis of ketone bodies and fatty acids via acetyl CoA and acetoacetyl CoA

glucogenic

________________ amino acids can give rise to glucose via gluconeogenesis intermediates

glutamate

glucogenic amino acid that forms alpha-ketoglutarate when deaminated

alanine

glucogenic amino acid that forms pyruvate when deaminated

aspartate

glucogenic amino acid that forms oxaloacetate when deaminated

leucine

ketogenic amino acid that ultimately forms acetyl CoA and Acetoacetate when deaminated

glycine

______________, through combination with succinyl CoA, is the precursor of heme

glutathione

Glutamate, cysteine, and glycine are the three amino acids that produce the biological antioxidant ___________________

arginine

a precursor of nitric oxide, an important vasodilator and neurotransmitter

glutamate

precursor of GABA, an inhibitory neurotransmitter

histidine

precursor of histamine, which is produced in asthma and allergic reactions

tryptophan

precursor of serotonin, in which there are low levels in depression and related disorders

tyrosine

precursor catecholamines: dopamine, epinephrine, and norepinephrine

dopamine

catecholamine that has low levels in parkinson's

epinephrine and norepinephrine

catecholamines that raise blood pressure and control many metabolic functions