| 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
|
| 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 |
HHS Shrek
