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MBC - Lecture 41

Nitrogen Incorporation, Amino Acids, and Urea (Douglas)

Lecture 41 Nitrogen Incorporation
Some amino acids are ___, and are derived from ___ sources. essential, exogenous
Amino acid catabolism generates ___, a nontoxic carrier of ___ atoms. urea, nitrogen
Urea synthesis occurs in the ___. liver
Amino acids ___ and ___ will carry amino carry amino acid nitrogen from ___ to the ___. alanine and glutamine, peripheral tissues to the liver
___ recovered from deamination of ___ in the liver provides glucose. Pyruvate, alanine
Key enzymes involved in nitrogen disposal are: transaminases, glutamate dehydrogenase, glutaminase
Humans make ___ non-essential amino acids de novo, and ___ essential amino acids from diet. 11, 10
Urea cycle consists of ___ steps, incorporating nitrogen from ___ and one from ___ into urea. 4, ammonia, aspartate
All essential amino acids are derived from corresponding ___. a-keto acids
___ supplement is only required during growth. Arginine
PVT TIM HALL Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine
Non-essential amino acids are derived by modification of metabolic intermediates from ___ and ___. glycolysis and TCA cycle
Modifications involve transfer of ___ and ___. amino groups and sulfur
Atmospheric nitrogen is converted to ___ and ___ by nitrogen fixing bacteria and algae. nitrate and ammonia
___ is fixed into amino acids and protein. Ammonia
Nitrogen balance is the measurement of ___ minus ___. consumption minus excretion
If consumption exceeds excretion, then nitrogen balance is ___. positive (i.e. rapid growth, recovery, etc.)
If excretion exceeds consumption, then nitrogen balance is ___. negative (i.e. protein malnutrition, fasting/starvation, essential amino acid deficiency)
___, ___, and ___ supplements are required in premature infants and liver disease. Cysteine, tyrosine, and arginine
___ is first produced in nitrogen excretion, but is toxic. Ammonia
___ are the major sources of free ammonia. Intestinal bacteria
Small amounts of ___, ___, and ___ are excreted. uric acid, creatinine, and ammonia
Majority of ammonia is converted to and excreted as ___. urea
BUN (___) measures ___ and ___ function. blood urea nitrogen, metabolism and renal function
>___% of nitrogen excreted as ___. >80%, urea
Transamination The major process for moving nitrogen among amino acids
___ is the major participant in transamination. Glutamate
All amino acids except ___ and ___ undergo transamination. lysine and threonine
___ (___) is the major cofactor for transaminases. Pyridoxyl phosphate (PLP)
Free ammonia in the ___ is incorporated into glutamate by ___. liver, glutamate dehydrogenase
Functional form of pyridoxal phosphate, vitamin ___, is covalently linked to various aminotransferases. vitamin B6
Linkage of vitamin B6 is displaced by amino acids ___ or ___. aspartate or glutamate
Drugs like ___ and ___ compete for donor amino acid binding, reducing transferase activity. antituberculosis and isoniazid
High levels of ___ in blood indicates liver damage. aminotransferases
AST/SGOT Glutamate Aspartate Transferase / Serum Glutamate Oxaloacetate Transaminase
ALT/SGPT Glutamate Alanine Transferase / Serum Glutamate Pyruvate Transaminase
___ is released during transamination of pyridoxal phosphate. Pyridoxamine
Key a-keto acid intermediates: Pyruvate, a-Ketoglutarate, Oxaloacetate
Oxidative Deamination Replace amino group with oxygen, free ammonia released
Dehydratase Remove water to form an imine, then water is re-added to form keto acid and ammonia
Oxidative reactions release ___ and require ___ (___) as a co-factor. free ammonia, flavin mononucleotide(FMN)
Dehydratase removes water and works on hydroxyamino acids ___ and ___. serine and threonine
Glutamate dehydrogenase operates near ___. equilibrium
___ reducing equivalents used in amination of a-ketoglutarate. NADPH
Glutamate dehydrogenase is a ___ reaction and can ___/___ ammonium to/from glutamate. reversible, release/incorporate
Glutamine and asparagine amides deaminated to glutamate and aspartate by ___ and ___. glutaminase and asparginase
Three enzymes that fix nitrogen into biomolecules: Glutamine Dehydrogenase, Glutamine Synthetase, Carbamoyl Phosphate Synthetase
Amino group of ___ is transferred from a-ketoglutarate during metabolic interconversion to yield ___ and ___. alanine, pyruvate and glutamate
Transamination of essential amino acids is ___. unidirectional
All transamination reactions involve ___ and ___. glutamate and a-ketoglutarate
Liver failure results in impaired ___ excretion (___ occurs). nitrogen excretion (hyperammonemia)
Glucose-Alanine Cycle Elimination of amino acids to the liver and return of carbons to peripheral tissues
Glutamine is synthesized by ___ to fix nitrogen in muscle for transport to the liver (some to intestine). glutamine synthetase
Glutaminase and glutamate dehydrogenase release ___ to the ___ cycle. nitrogen to the urea cycle
Urea synthesis occurs in the ___. liver
Nitrogen in urea comes from ___ and ___. ammonia and aspartate
Carbamoyl Phosphate Synthetase I (CPS I) Catalyzes formation of carbamoyl phosphate in the mitochondria from ammonia (released from glutamine), 2 ATP, and carbon dioxide
Deficiency of CPS I leads to: High blood concentrations of ammonia and related toxicity
CPS I requires ___ as a co-factor. N-acetylglutamate
Carbamoyl Phosphate Synthetase II (CPS II) Cytosolic form of CPS that does not require N-acetylglutamate
Ornithine Transcarbamoylase (OTC) (Transferase) Catalyzes formation of citrulline in the mitochondria from ornithine and carbamoyl phosphate, releasing a Pi
Deficiency of ornithine transcarbamoylase leads to: high blood concentrations of ammonia and orotic acid, as carbamoyl is shunted to pyrimidine biosynthesis
Argininosuccinate Synthetase (Ligase) Catalyzes formation of argininosuccinate in the cytosol from citrulline and aspartate, requiring an ATP that is cleaved to AMP + PPi
Deficiency of argininosuccinate synthetase leads to: high blood concentrations of ammonia and citrulline
Argininosuccinase (Lyase) Catalyzes cleavage of argininosuccinate in the cytosol to arginine and fumarate
Deficiency of argininosuccinase leads to: high blood concentrations of ammonia and citrulline
Arginase (Hydrolase) Catalyzes cleavage of arginine in the cytosol to ornithine and urea
Deficiency of arginase leads to: high blood concentrations of ammonia and arginine
If CPS I is limiting/defective, nitrogen is driven through ___ into the ___ pathway, forming orotic acid detectable in blood and urine. CPS II into the pyrimidine pathway
The urea cycle is ___ in times of starvation. up-regulated
CPS I is allosterically activated by ___. N-acetylglutamate
___ stimulates N-acetylglutamate synthetase. Arginine
Ammonia Toxicity Ammonia encephalopathy/cerebral edema, treat with benzoate/phenylacetate, control nitrogen intake(avoid endogenous protein breakdown), a-keto acid diet
CPS I/N-Acetylglutamate Deficiency Hyperammonemia/encephalopathy/respiratory alkalosis, autosomal recessive, fatal in infants with possible delayed onset
OTC Deficiency Mental Retardation/Death (NH3 accumulation), X-linked, most common urea cycle defect
Arginosuccinate Synthetase Deficiency Severe hyperammonemia/increased citrulline in blood and urine, autosomal recessive, treat with low protein and arginine supplements
Therapy for partially defective urea cycle involves: limit protein intake, remove excessive NH3 with compounds (benzoate and phenyl acetate) that covalently bind and are excreted, replace missing urea cycle intermediates, liver transplant
Majority of protein breakdown occurs in ___. skeletal muscle
Urea is transported from the ___ to the ___. liver to the kidney
The kidney excretes ___, ___, and ___. ammonia, glutamate, and urea
Fumarate can be used in formation of ___ and __, or the reformation of ___. ATP and glucose, aspartate
Created by: emyang



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