Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CPR Exam 2 > Nitrogen Metabolism > Flashcards

Nitrogen Metabolism Flashcards

1
Q

IEM of amino acid transport can result in what?

A

Intestinal malabsorption and aberrant renal reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where does amino acid and glucose reabsorption occur in the kidney?

A

Occurs in the PCT
As the filtrate passes through the PCT transport proteins from the SLC (solute carrier) gene superfamily mediate reuptake of amino acids and glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is hartnup disease?

A

Autosomal recessive disorder caused by a defect in transporter of neutral amino acids
Affects absorption/reabsorption of neutral amino acids
Aminoaciduria: Ala, Ser, Thr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn excreted 5-10x the normal level
Also known as pellagra-like dermatosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Deficiency of which vitamin is also seen with Hartnup disease?

A

Niacin deficiency

Trp is a precursor for serotonin, melatonin and niacin (which is a precursor for NAD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does Hartnup disease manifest in infancy?

A

As failure to thrive, nystagmus (rapid and repetitive eye movement), intermittent ataxia, tremor and photosensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What can trigger Hartnup disease?

A

Sunlight, fever, drugs or emotional or physical stress

Period of poor nutrition almost always precedes an attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How is Hartnup disease treated?

A

With a repletion of niacin including a high protein diet and daily nicotinamide supplementation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Trp is an important precursor for which molecules?

A

Niacin (needs Vit B6)
Serotonin and melatonin
Affected in hartnup disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is cystinuria?

A

Autosomal recessive defects in the reabsorption of dimeric amino acid cystine
Also defects in reabsorption of dibasic amino acids Arg, Lys and ornithine (COAL)
Results in the formation of cystine renal calculi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the pt presentation for cystinuria?

A

Renal colic (abdominal pain that comes in waves and is linked to kidney stones)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

During cystinuria, COAL is not reabsorbed and the concentration of amino acids rise where?

A

In the tubular lumen as the glomerular filtrate passes through the nephron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the main metabolic byproduct in extrahepatic tissues and the most prevalent nitrogen transporter in the blood?

A

Glutamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Amino acids are converted to glutamate via what?

A

Transamination reactions via PLP as a cofactor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What causes classic phenylketonuria (PKU)?

A

Deficient/defective phenylalanine hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What causes secondary (non-classical) PKU?

A

Dihydrobiopterin reductase deficiency
Deficiency of tetrahydrobiopterin (cofactor of PAH)
Defects in synthesis or regeneration of BH4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the most common IEM?

A

Phenylketonuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What occurs with phenylketonuria?

A

Phe is instead converted to phenylpyruvate and then phenyllactate (causes musty odor in urine) and phenylacetate
Latter tow disrupt neurotransmission and block aa transport in teh brain as well as myelin formation resulting in severe impairment of brain function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is PKU treated?

A

Dietary limit of Phe
Protein supplied with synthetic formula supplemented with Tyr
Improved metabolic control when treated with tetrahydrobiopterin (cofactor of PAH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

When the body has enough PAH this enzyme will convert Phe into what?

A

Tyrosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Diagnosis and initiation of dietary treatment of classical PKU must occur when?

A

Before the child is 2 weeks of age in order to prevent intellectual disability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the role of THB (BH4)?

A

It is an essential cofactor in hydroxylation of aromatic aa Phe, Tyr and Trp
It is regenerated by the reduced form of NADPH dependent reduction of qBH2 catalyzed by dihydrobiopterin reductase
Defects in biosynthesis or regeneration of THB lead to secondary PKU

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Production of which NTs is also disrupted with deficient THB?

A

Monoamine NTs such as dopamine, NE and serotonin from Tyr and Trp which leads to neurologic dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How is secondary PKU treated?

A

With synthetic THB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are tyrosinemias?

A

Elevated blood levels of tyrosine

Transient tyrosinemia in newborns is attributed to delayed expression of enzymes necessary for Tyr catabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which dietary restrictions are taken for tyrosinemias?

A

Restrictions of Phe and Tyr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is tyrosinemia type I?

A

Defect in fumarylacetoacetate hydrolase

MC and requires a liver transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the effects of tyrosinemia type I?

A

Infants will have a cabbage like smell and develop severe liver failure without treatment
Formation of succinylacetone (toxic to liver and kidney) interferes with the TCA cycle causes renal tubule dysfunction and inhibits the biosynthesis of heme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the go to treatment for type I tyrosinemias?

A

Nitisinone (a 4-HPPD inhibitor)

29
Q

What is type II tyrosinemia?

A

Attributed to defective tyrosine aminotransferase

30
Q

What are the manifestations of type II tyrosinemias?

A

Palmar and plantar hyperkeratosis, corneal lesions (tyrosine deposition), and intellectual disability
Ocular manifestations including excessive tearing, redness, pain and photophobia

31
Q

What is tyrosinemia type III?

A

Attributed to defective 4-HHPD and results in various neurological findings
Very rare
Confirmed by hypertyrosinema and elevated 4-hydroxyphenylpyruvate and its metabolites

32
Q

What is alkaptonuria?

A

Due to defective homogentisate oxidase (an enzyme invovled inn the Tyr degradation pathway)
Autosomal recessive disease
“Black urine” or “black bone” disease

33
Q

What does alkaptonuria cause?

A

Causes homogentistic acid to accumulate
Auto-oxidation of homogentistic acid (by light) and polymerization of the products produce dark colored pigments in the urine
Black pigmentation in the IV discs along with degenerative arthritis and ochonosis (dark sclera) are also observed

34
Q

What is the characteristic triad of alkaptonuria?

A

Homogentistic aciduria, ochronosis and arthritis

35
Q

What amino acid is the key nitrogen flow regulator (both a nitrogen acceptor and nitrogen donor)?

A

Glutamate

36
Q

What is ammonia toxicity?

A

Excessive ammonia due to disorders in the urea cycle or liver failure can have highly toxic effects on the brain and CNS
Causes pH imbalance, swelling of astrocytes in the brain which leads to cerebal edema and intracranial HTN
Also causes mitochondrial dysfunction

37
Q

What are the other effects of ammonia toxicity?

A

TCA cycle is inhibited due to depletion of alpha ketoglutarate (disrupts production of ATP)
Postsynaptic excitatory proteins are inhibited which depresses CNS function
Depletion of glutamate results in disruption of its NT activity (key reactant in formation of GABA)

38
Q

Typically the alpha ketoglutarate to glutamate reaction doesnt occur outside the what?

A

Brain as glutamate dehydrogenase equilibrium favors the production fo ammonia and alpha ketoglutarate

39
Q

Glutamate dehydrogenase has a very low affinity for what?

A

Ammonia and therefore toxic levels of ammonia would have to be present in the body for the forward reaction to process (alpha ketoglutarate and ammonia to glutamate and NADP)

40
Q

In the brain the NAD/NADH ratio in mitochondria encourages what?

A

Oxidative deamination of glutamate to alpha ketoglutarate and ammonia

41
Q

Gout is characterized as high levels of what in the blood?

A

Uric acid

42
Q

What is primary hyeruricemia?

A

Overproduction of uric acid

43
Q

What is secondary hyperuricemia?

A

Underexcretion of uric acid

44
Q

What does gout result in?

A

Extremely painful deposits of Na irate in the joints of the extremities (gouty arthritis)
Na urate deposits in the kidneys also occur that can cause damage

45
Q

What can trigger episodes of gout?

A

Diets rich in purines (beans, spinach and lentils) along with alcohol, meat and seafood

46
Q

Acidemia stimulates reabsorption of what?

A

Uric acid in the kidney via urate transporter URAT1

47
Q

What is used to treat gout?

A

Use of colchicine that decreases movement of granulocytes to affected areas
Also the use of allopurinol that inhibits xanthine oxidase and might also increase the levels of more soluble purines hypoxanthine and guanine

48
Q

Altered uric acid excretion can result from what?

A

Decreased glomerular filtration, decreased tubular secretion or enhanced tubular reabsorption

49
Q

Decreased tubular secretion occurs in pts with what?

A

Acidosis (e.g. DKA, ethanol or salicylate intoxication, starvation ketosis)
Organic acids that accumulate in these conditions compete with urate for secretion

50
Q

What is the RLS of the urea cycle?

A

Conversion of NAG into carbamoyl phosphate via carbamoyl phosphate synthetase

51
Q

What is the action of NAG synthase?

A

Produces NAG from glutamate and acetyl CoA

52
Q

What is the result of the lack of NAG synthase?

A

Excessive accumulation of nitrogen in the form of ammonia in the blood causing hyperammonemia
Sx: vomiting, refusal to eat, progressive lethargy and coma

53
Q

What is hyperammonemia?

A

Occurs with defects in any of the 6 enzymes associated with the urea cycle or with 2 specific transporters (which cause more severe forms)

54
Q

What do defects in ornithine transcarbamoylase (X linked) cause?

A

Excess carbamoyl phosphate which can then spill out into the cytoplasm
Then metabolized by pyrimidine synthesis pathway to orotic acid which then accumulates and excreted in the urine —> hyperammonemia and decreased BUN

55
Q

What is the treatment for hyperammonemia?

A

Limiting protein consumption and the use of agents that can conjugate excessive components and promote excretion

56
Q

What are the 6 enzymes of the urea cycle that can cause hyperammonemia?

A 
CPS1
Ornithine transcarbamoylase (OTC) 
Argininosuccinic acid synthetase (ASS1) 
Argininosuccinic acid lyase (ASL) 
Arginase (ARG1) 
NAGS
57
Q

What two amino acid transporters are associated with hyperammonemia?

A 
Ornithine translocase (ORNT1; ornithine/citrulline carrier) 
Citrin (aspartate/glutamate carrier)
58
Q

Describe the role of carbamoyl phosphate synthetase II

A

Cytosolic enzyme
Involved in the first step of de novo pyrimidine synthesis
Doesnt require NAG like its mitochondria counterpart
Stimulated by PPPP and inhibited by UTP
Orotic acid is an intermediate in the synthesis pathway of UMP via cytosolic CPS II

59
Q

A defect in UMP synthase can lead to what?

A

Accumulation of origin acid and result in orotic aciduria
Unlike defects in ornithine transcarbamoylase, orotic aciduria from UMP synthase deficiencies is not accompanied by hyperammonemia or reduced BUN levels

60
Q

Describe CPSase I

A

Involved in urea cycle
Mitochondrial
NAG activated

61
Q

Describe CPSase II

A

Involved in pyrimidine synthesis
Cytosolic
PRPP activated

62
Q

What can occur in some infants that are born prematurely?

A

May have a developmental deficiency in UDP glucoronyl transferase
Leads to increased levels of unconjugated bilirubin coupled with high bilirubin load

63
Q

What is gray baby syndrome?

A

Infants who develop infections are treated with an anti-microbial known as chloramphenicol
Deficiency in UDP-glucuronyl transferase causes them to be incapable of metabolizing the excessive drug load
Insufficient renal excretion of the unconjugated drug

64
Q

What does gray baby syndrome lead to?

A

Circulatory collapse due to impaired myocardial contractility
Directly interferes with tissue respiration and oxidative phosphorylation

65
Q

Conjugated (direct) bilirubin can be directly what?

A

Assayed whereas unconjugated (indirect) bilirubin cannot

66
Q

Describe jaundice in newborns

A

Elevated bilirubin is normal after brith
Most newborns have jaundice
Most noticeable 2-4 days after delivery
Return to normal 7-10 days after delivery

67
Q

Severe jaundice may occur if there is an increase need to replace the number of RBCs due to what?

A 
Abnormal blood cell shapes (sickle cell anemia) 
Rh or type incompatibility (hemolysis) 
Cephalohematoma (traumatic brith) 
Higher levels of RBCs, small for gestational age (SGA) 
Infection 
Enzymatic deficiencies 
Premature birth 
Hemolytic anemias
68
Q

Blue fluorescent light is used as a treatment for jaundice because it allows for what?

A

Photochemical conversion of bilirubin to water soluble isomers

69
Q

Pathologic (non physiologic) jaundice can be secondary to what?

A

Medications, infections (rubella, syphilis, sepsis), disease that affect the liver or biliary tract (CF, hepatitis), hypoxia, many different genetic or inherited disorders and perinatal trauma

CPR Exam 2 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions