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WVSOM -- Biochem
WVSOM -- Protein and AA Metabolism and the Urea Cycle
Question | Answer |
---|---|
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 |