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WVSOM -- Biochem

WVSOM -- Protein and AA Metabolism and the Urea Cycle

Patient with Hepititis A has what type of elevated bilirubin levels? indirect Bilirubin
Why is nitrogen metabolism important? We need amino acids and they cannot be stored.
Is nitrogen secreted? not generally
What are amino acids broken down for? fuel or building blocks glucose and lipid synthesis
What does the breakdown of amino acids generate? ammonia
Is ammonia toxic? yes
What is ammonium? NH4, an ion
What will cross the cell membrane, ammonia or ammonium? ammonia
pK is 9.3 so at pH 7 which form predominates, ammonia or ammonium? ammonium
Why is ammonia toxic? It increases pH which alters redox balance and can disrupt protein structure/function as well as inhibiting oxidative phosphorylation by breaking down the H+ gradient
Where do we get our amino acids? dietary proteins, endogenous protein and endogenous AA synthesis
What do amino acids break down into? carbon and nitrogen
What do we do with carbon from AA degeneration? energy and synthesis of glucose, FA and ketones
What do we do with nitrogen from AA degeneration? urea
What do we synthesis with amino acids? N-containing molecules such as purines, pyrimidines, porphyrins, neurotransmitters, etc.
What is Nitrogen Balance? nitrogen input – nitrogen output
What is positive N balance? input > output
What is negative N balance? input<output
When do we see a positive N balance? Childhood and pregnancy
When do we see a negative N balance? dietary deficiency and catabolic stress
What are the 10 essential amino acids? phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, lysine, leucine
What is the neumonic for remembering the 10 essential amino acids? PVT TIM HALL
Why is histidine an essential amino acid when it is synthesized in the urea cycle? It is needed for growth and we don’t make enough
How is aspartate synthesized? transanimation from oxaloacetate
Tyrosine is made from? phenylalanine
Arginine is generated in? the urea cycle
Glutamine is made from? transanimation of glutamate
What are aminotransferases? intracellular proteins not usually found in plasma. It is a transaminase
What are the tree cofactors important for AA synthesis? pyridoxal phosphate, tetrahydrofolate and tetrahydroblopterin
Why is pyridoxal phosphate important? for reactions involving the amino group (transamination and deamination)
What is tetrahydroblopterin required? BH4 is required for synthesis of tyrosine from phenylalanine
Where does protein digestion start? stomach. HCl denatures the proteins to free AA
Where are free AA absorbed? small intestine
How are AA absorbed in the small intestine? facilitative diffusion and secondary active transport
What is done with incompletely digested protein? utilized by bacteria releasing ammonia
How are AA transported? Na dependent AA carriers
What is cystinurea? defect in a transporter for cysteine and basic AA that results in kidney stones?
What is Hartnup disease? defect in the transporter for neutral AA generally asymptomatic
What happens to the amino acids we dno’t need for protein synthesis? amino group is removed thru transamination or deamination
What is more common transamination or damination? transamination
What catalizes transamination? aminotransferases
What is transamination? conversino from keto acid to amino acid or vice versa
What does Aspartate go to? asparagine
What does pyruvate go to? alanine
What does serine go to? glycine or cysteine
What does glutamate go to? Glutamine
Glutamate semialdehyde goes to? proline and arginine
How is pyridoxal phosphate synthesized and where? In the liver from vitamin B6
What is B6 deficiency associated with? drugs, alcoholism and starvation
how does glutamate get rid of the nitrogen? Damination by glutamate dehydrogenase(GDH)
What is produced when glutamate is deaminated? ammonia and alpha-ketoglutarate
Where does deamination of glutamate occur? liver and kidney
Deamination of glutamate results in… Glutamate + NH4 -> Alpha ketoglutinate + Ammonium
How many ammonium molecules does glutamine carry to the liver? 2
What is pyruvate transaminated to? alanine
What does alanine give an amino group to in order to go back to pyruvate? glutamate
Nitrogen component in AA catabolism is transferred to _________ where it is carried to the liver. glutamate and glutamine
What are glucogenic AA? degraded to pyruvate or TCA cycle intermediates
What are ketogenic AA? degraded to acetyl CoA or acetoacetate
What does insulin promote with AA? uptake and protein synthesis
What do glucocorticoids induce? ubiquitin synthesis
Cortisol stimulates? gluconeogenesis
Glucagaon and cortisol stimulate uptake of AAs into the liver
What tissues metabolize AAs more rapidly? kidney, brain, gut, immune cells
What hormone will lead to muscle wasting in fasting state? cortisol
What is a hypercatabolic state? state of increased fuel usage
What may cause a hypercatabolic state? surgery, infection, trauma
What does the brain need AA for? synthesis of neurotransmitters
What is a major source of AA in the fasted state? muscle
What is the important hormone in a hypercatabolic state? cortisol
What is urea? disposal form of ammonia
Where is urea made? urea cycle
What enzyme is used to go from ornithine to citrulline? OTC Ornithine transcarbomylase
What enzyme is needed to go from HCO3 + NH4 -> Carbaoyl phosphate? Carbamoyl Phospahte synthase 1
Is the synthesis of urea reversible? no
Where do the first two steps of urea cycle take place? mitochondria
What is the rate limiting step? CPS1
What links the TCA cycle to the urea cycle? fumerate
What is regenerated in the urea cycle? ornithine
Where does the urea cycle primarily take place? liver
Is ATP used in urea cycle? yes
Where do the two N come from? Ammonia and aspartate
How many N come from the urea cycle? 2
How is the urea cycle regulated? based on substrate availability (feed forward)
What kind of diet induces urea cycle enzymes? high protein or prolonged fasting
What stimulates CPS1? NAG (n-acetylglutamate)
What synthesizes NAG? aceytl CoA and glutamate
What happens to the urea produced in urea cycle? crosses membranes and diffuses into the blood and is then filtered by the kidneys. Some diffuses into intestines where it is cleaved by bacteria
What is Blood urea Nitrogen? BUN is a measure of urea concentration in the blood. Reflects function of the kidney and liver.
A patient is suffering from kidney failure. Would this patient have elevated or reduced BUN? elevated
Urea cycle impairment results in? hyperammonemia
What is hyperammonemia? increased blood levels of ammonia
What are symptoms of hyperammonemia? tremors, agitation, slurring of speech, blurred vision, vomiting, hypotonia, sezures, mental retardation, cerebral edema, coma
What is the most common urea cycle disorder? OTC, ornithine transcarbamylase deficiency
What is OTC? Ornithine transcarbamylase deficiency which is X-linked
How are hereditary urea cycle disorders passed on (except OTC)? Autosomal recessive
Created by: tjamrose
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