30. Amino acid disorders + Urea cycle

Question 1

Phenylketonuria results from

Answer 1

dec phenylalanine hydroxylase or

dec tetrahydrobiopterin

Question 2

tyrosine becomes essential

and phenyalanine accumulates

Answer 2

phenylketonuria

Question 3

tx of phenylketonuria

Answer 3

dietary control to dec phenylalanine and

inc tyrosine

Question 4

congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine, leading to build up of homogentisic acid

Answer 4

alkaptonuria

Question 5

defective melanin synthesis from tyrosine which may be from
•defective tyrosine transporters
•absence of copper requiring enzyme tyrosinase

Answer 5

albinism

Question 6

defect in methionine degradation

Answer 6

homocystinuria

Question 7

• high plasma and rinary levels of homocysteine and methionine
• low levels of cysteine

Answer 7

homocystinuria

Question 8

tx of homocystinuria

Answer 8

restriction of methionine

supplementation with vit B6,B12 and folate

Question 9

methionine synthase co-enzyme

Answer 9

methylcobalamin

Question 10

cystathionine ß-synthase co-enzyme

Answer 10

pyridoxal phosphate

Question 11

Homoysteine –> methionine requires

Answer 11

methionine synthase

co-enzyme: methylcobalamin

Question 12

Homocysteine –> cystathionine

Answer 12

cystathionine ß-synthase

coenzyme:pyridoxal phosphate

Question 13

caised by
•deficiency of cystathione ß–synthase enzyme
•defective methylcobalamin synthesis
•or abnormality in methylene tetrahydrofolate reductase

Answer 13

Homocystinuria

Question 14

inherited defect of the renal tubular amino acid transporter for cystine, ornithine, lysine, arginine in the PCT of kidneys

Answer 14

cystinuria -CORK

Question 15

tx of cystinuria

Answer 15

acetazolamide to alkalinize the urine

Question 16

defect in the conversion of methylmalonyl coa to succinyl coa
•involves metabolism of isoleucine, valine, threonine and methionine

Answer 16

methylmalonyl coa mutase deficiency

IVTM

Question 17

blocked degradation of branched amino acids (Isoleucine, valine and leucine) due to alpha ketoacid dehydrogenase complex

Answer 17

maple syrup urine disease

Question 18

tx of MSUD

Answer 18

dietary restriction of valine, isoleucine and leucin to the minimum

Question 19

• severe mental retardation
• fair skin and eczema
• musty body odor

Answer 19

phenylketonuria

Question 20

black urine on standing

Answer 20

alkaptonuria

Question 21

accumulation of phenylketones
•phenylpyruvate
•phenyllactate
•phenylacetate - characteristic odor to urine

Answer 21

phenylketonuria

Question 22

• dark connective tissue (ochronosis)

* may have debilitating arthralgias

Answer 22

alkaptonuria

Question 23

absence of pigment from hair, eyes skin

inc risk of skin cancer

Answer 23

albinism

Question 24

ectopia lentis 
faulty bone development
mental retardation
tendency to form thrombi
MI 
stoke in children and young adults

Answer 24

homocystinuria

Question 25

this amino acid disorder can cause staghorn calculi

Answer 25

cystinuria-cystine kidney stones

Question 26

seizure, encephalopathy, | and stroke at age of 1 month to 1 year

Answer 26

methylmalonyl coa mutase deficiency

Question 27

sweet odor in urine vomiting seizures mental retardation

Answer 27

maple syrup urine disease

Question 28

conversion of the body’s nitrogenous waste to urea

Answer 28

urea cycle

Question 29

where does urea cycle occur

Answer 29

* in the liver only | * mitochondria and cytosol of hepatocytes

Question 30

what are the substrates of urea cycle

Answer 30

* NH3 (derived from oxidative deamination of glutamate) * aspartate * CO2 * 3 ATP

Question 31

what is the product of urea cycle

Answer 31

urea; fumarate; H2O

Question 32

what is rate limiting step of urea cycle

Answer 32

NH3 + CO2 –> carbamoyl phosphate enz: carbamoyl phosphate synthetase I Allosteric activator: N-acetylglutamate

Question 33

Enzymes of the urea cycle and location of the reaction

Answer 33

1. carbamoyl phosphate synthetase I (mitochondria) 2. Ornithine transcarbomylase (mitochondria) 3. arginosuccinate synthetase (cytosol) 4. arginosuccinate lyase (cytosol) 5. arginase (cytosol)

Question 34

synthesis of 1 mol of urea requires ___ ATP ___ high energy bonds

Answer 34

* 3 ATP | * 4 high energy bonds

Question 35

urease positive bacteria convert urea to

Answer 35

CO2 and NH3

Question 36

Fates of urea

Answer 36

1. urea-> kidney-> excretion in the urine | 2. some urea -> intestine -> urease positive bacteria –> CO2 + NH3

Question 37

amount of urea excreted each day by a healthy adult

Answer 37

30 g

Question 38

urea accounts for ___% of nitrogenous excretory products

Answer 38

90%

Question 39

ammonia travels to the liver mainly in the form of

Answer 39

alanine and glutamine

Question 40

provide nitrogen that is used to produce urea

Answer 40

NH4+ | and aspartate

Question 41

serves as a carrier that is generated by urea cycle

Answer 41

ornithine

Question 42

carbamoyl phosphate synthase I is located in this organelle

Answer 42

mitochondria

Question 43

carbamoyl phosphate synthase I | activated by

Answer 43

N-acetylglutamate

Question 44

location of ornithine transcarbamoylase

Answer 44

mitochondria

Question 45

this is transported in the cytosol in exchange for cytoplasmic ornithine

Answer 45

citrulline

Question 46

formation of arginosuccinate

Answer 46

citrulline + aspartate –> arginosuccinate ATP -> AMP + iP enz: arginosuccinate synthetase

Question 47

formation of arginine

Answer 47

argininosuccinate –> arginine + fumarate | Enz: argininosuccinate lyase

Question 48

fumarate from reaction 4 of urea cycle can be converted to ___

Answer 48

fumarate –> malate –> glucose (fasting state) fumarate –> oxaloacetate –> oxaloacetate –> (via transamination) aspartate

Question 49

arginine is cleaved for form

Answer 49

Arginine –> Urea + Ornithine | Enz. arginase

Question 50

inhibitor of arginase

Answer 50

ornithine

Question 51

when the cell requires additional ornithine, it is sythesized from

Answer 51

glucose via glutamate

Question 52

arginine can be synthesized from

Answer 52

a. first 4 rxns of urea cycle | b. glucose via ornithine

Question 53

Converts ammonium and bicarbonate into carbamoyl phosphate. This is the rate-limiting step in the urea cycle. This reaction requires two ATP and occurs in the mitochondria.

Answer 53

Carbamoyl phosphate synthetase I

Question 54

Combines ornithine and carbamoyl phosphate to form citrulline. Located in mitochondria.

Answer 54

Ornithine transcarbamoylase

Question 55

Condenses citrulline with aspartate to form arginosuccinate. This reaction occurs in the cytosol and requires one ATP.

Answer 55

Argininosuccinate synthetase

Question 56

Splits argininosuccinate into arginine and fumarate. Occurs in the cytosol.

Answer 56

Argininosuccinate lyase

Question 57

Cleaves arginine into one molecule of urea and ornithine in the cytosol. The ornithine is then transported back into the mitochondria for entry back into the cycle.

Answer 57

Arginase

Question 58

Although the liver normally has a great capacity for urea synthesis, the enzymes of the urea cycle are induced if a high-protein diet is consumed for ______

Answer 58

4 days or more

Question 59

Purpose of urea cycle

Answer 59

allows for the excretion of NH4+ by transforming ammonia into urea, which is then excreted by the kidneys.

Question 60

occurs when there is a deficiency in one of more of the urea cycle enzymes, causing insufficient removal of NH4+.

Answer 60

Hyperammonemia

Question 61

Neurotoxic effects - Hyperammonemia

Answer 61

``` Tremors slurring of speech vomiting blurring of vision cerebral edema somnolence coma death ```

Question 62

most common cause of hereditary hyperammonemia

Answer 62

ornithine transcarbomylase deficiency

Question 63

most severe cause of hereditary hyperammonemia

Answer 63

carbamoyl phosphate synthase-1 deficiency

Question 64

Hereditary hyperammonemia is characterized by

Answer 64

hyperammonemia elevated glutamine dec BUN respiratory alkalosis

Question 65

tx of hereditary hyperammonemia

Answer 65

1. restriction of dietary protein | 2. phenylbutyrate –> phenylacetate, which binds to glutamine and is excreted as phenylglutamine

Question 66

Acquired hyperammonemia is seen in

Answer 66

adults with compromised liver fx | cirrhosis : portal blood is shunted directly to systemic circulation without passing through the liver

Question 67

purely ketogenic aa | can be converted to form acetyl coa or acetoacetyl coa

Answer 67

Lysine , Leucine | KL-keto

Question 68

Glucogenic and ketogenic amino acds | can be converted to form acetyl coa or acetoacetyl coa, pyruvate or intermediates of krebs cycle

Answer 68

phenylalanine tyrosine Isoleucine Tryptophan FYIW -both