Chapter 17 ( Amino Acid Metabolism )

Question 1

Where does the 2 nitrogens of urea coming from ?

Answer 1

One from Aspartate and the other from Amino group which either comes from glutamine or glutamate

Question 2

What is the major carrier of excess nitrogen from tissues ?

Answer 2

Glutamine

Question 3

By what is kidney glutaminase induced ?

Answer 3

Chronic acidosis , in which excretion of ammonium may become the major defense mechanism

Question 4

What does AST/ALT >1 indicate ?

Answer 4

Alcohol abuse

Question 5

Carbamoyl phosphate synthase l ? Its obligate activator ?

Answer 5

Uses NH4 + HCO3 + 2 ATP to form carbamoyl phosphate

Obligate activator : N-acetylglutamate which produced only when free amino acids are present

Question 6

Ornithine transcarbamoylase ?

Answer 6

Part of the urea cycle present in mitochondrial matrix

Transform Carbamoyl phosphate using ornithine into Citrulline

Question 7

What does happen to aspartate in urea cycle ?

Answer 7

Enter the cycle in the cytoplasm and leaves it minus its amino group as Fumarate , which if gluconeogenesis is active can be converted to glucose

Question 8

Similarities and differences between Carbamoyl phosphate synthase deficiency and Ornithine transcarbamoylase deficiency ? Ttt ?

Answer 8

Similarities : Hyperammonemia , increased blood glutamine , decreased BUN , lethargy convulsions coma death 
Differences : 
OTC deficiency : X-linked recessive 
With Orotic aciduria 
CPS deficiency : autosomal recessive 
Without orotic aciduria 
Ttt : low protein diet 
Administration of sodium benzoate or phenylpyruvate to provide an alternative route for capturing and excreting excess nitrogen

Question 9

Phenylketonuria defect ? Symptoms ? Screening ? Ttt ? Affected pregnant issues ?

Answer 9

Defect : Phenylalanine hydroxylase deficiency
Symptoms : mental retardation , autistic symptoms , loss of motor control , children may have pale skin and white - blond hair
Screening test after birth : blood phenylalanine level
Ttt : lifelong semisynthetic diet restricted in phenylalanine and avoidance of Aspartame
Uncontrolled affected pregnant have children with mental retardation, microcephaly and low birth weight

Question 10

Albinism defect ?

Answer 10

Tyrosinase enzyme deficiency which convert tyrosine to melanin

Question 11

Alkaptonuria defect ? Symptoms ?

Answer 11

Defect : Homogentisate oxidase deficiency which leads to high levels of homogentisic acid in blood 
Symptoms : 
Dark urine 
Ochronosis ( black cartilage ) 
Arthritis

Question 12

Maple syrup urine disease defect ? Symptoms ? Ttt ?

Answer 12

Defect : Branched-chain ketoacid dehydrogenase deficiency
Symptoms :
Urine has odor of maple syrup and caramel color
Mental retardation
Abnormal muscle tone
Ketosis , coma , death
Ttt : restricting dietary valine , leucine , isoleucine

Question 13

What substances is accumulating in propionyl CoA carboxylase deficiency ?

Answer 13

Propionic acid
Methyl citrate
Hydroxypropionic acid

Question 14

What substances is accumulating in Methylmalonyl CoA mutase deficiency ?

Answer 14

Methylmalonic acid ( methylmalonic aciduria )

Question 15

Homocystinemia defect ? Symptoms ? Diagnostic test ? Ttt ?

Answer 15

Defect : Cystathionine synthase deficiency
Or Vitamins deficiency as Folate , B12 , B6
Symptoms : deep vein thrombosis
Stroke , atherosclerosis
Marfan-like habitus
Mental retardation
Joint contractures
Diagnostic test : cyanide nitoprusside test of urine indicates homocystinuria
Ttt : restriction of methionine in diet
And supplement of Folate , B12 , B6 vitamins in diet

Question 16

Difference between Marfan and homocystinemia in lens subluxation direction ?

Answer 16

Marfan : upward and outward

Homocystinemia : downward and inward

Question 17

Important uses of SAM ? Its fate after donating the methyl group ?

Answer 17

Important uses :
1- synthesis of epinephrine
2- synthesis of 7-methylguanine cap on eukaryotic mRNA
Its fate : converted to homocysteine and the remethylated by N-methyl THF-homocysteine methyltransferase which requires B12 and N-methyl THF , the methionine can be used again to make SAM

Question 18

Tetrahydrobiopterin (BH4) is necessary for which enzymes ? Regenerated by what ?

Answer 18

Tyrosine hydroxylase
Phenylalanine hydroxylase
Tryptophan hydroxylase ( serotonin synthesis )
Regenerated by dihydropetridine reductase

Question 19

Vitamin B12 deficiency causes demyelination of what in the spinal cord ?

Answer 19

Posterior columns

Lateral corticospinal tracts

Question 20

What are the heme proteins ?

Answer 20

Hemoglobin 
Myoglobin 
All the cytochromes 
Catalase 
Peroxidase 
Soluble guanylate cyclase

Question 21

The rate limiting enzyme of heme synthesis ? Its inhibitor ? Activator ?

Answer 21

Sigma-aminolevulinate (ALA) synthase
Inhibitor : heme
Activator : Vit B6

Question 22

Acute intermittent porphyria defect ? Mode of inheritance ? Symptoms ? Episodes induced by what ?

Answer 22

Defect : Porphobilinogen deaminase deficiency
Autosomal dominant with variable expression
Symptoms : NO PHOTOSENSITIVITY
Anxiety , paranoia , depression
Acute abdominal pain
Port-wine colored urine in some patients
Motor , sensory , autonomic neuropathy
Excretion of ALA and Porphobilinogen during episodes
Episodes induced by hormonal changes and many drugs as Barbiturates

Question 23

Porphyria cutanea tarda defect ? Mode of inheritance ? Symptoms ?

Answer 23

Defect : Uroporphyrinogen decarboxylase deficiency
Autosomal dominant with late onset
Symptoms : PHOTOSENSITIVITY
Blistering , inflammation , shearing in sun exposed skin
Hyperpigmentation
Red brown to deep red urine
Exacerbated by Alcohol

Question 24

Mechanism of Barbiturates exacerbation of porphyria ?

Answer 24

Barbiturates are hydroxylated by microsomal cytochrome P-450 system in the liver to be eliminated , so administration of barbiturates stimulates cytochrome P-450 synthesis , which in turn reduces heme level which lessens suppression of ALA synthase causing more porphyrin precursor synthesis .

Question 25

What enzymes do Lead poisoning affects ? Symptoms ?

Answer 25

ALA dehydrase
Ferrochelatase
Symptoms :
Anemia , coarse basophilic stippling of erythrocytes
Headache , memory loss , abdominal pain
Increased urinary ALA and free erythrocyte protporphyrin

Question 26

What does failure of insertion of Fe into protoporphyrin lX result in ?

Answer 26

Nonenzymatic insertion of Zn into protoporphyrin to form zinc-protoporphyrin which is extremely fluorescent and easily detected

Question 27

Hemochromatosis mechanism , organs affected , ttt ?

Answer 27

Mechanism : daily intestinal absorption of 2-3 mg of iron and after 20-30 years will result in 20-30 gram of iron in the body
Organs affected : liver , pancreas , skin , joints
Ttt : phlebotomy , Deferoxamine

Question 28

Kernicterus cause ?

Answer 28

At very high levels , lipid soluble bilirubin may cross the BBB and precipitate in Basal Ganglia causing irreversible brain damage .

Question 29

Conditions that increase indirect bilirubin ?

Answer 29

Hemolysis 
Cigler-Najjar syndrome ( defect in UDP-glucuronyl transferase 
Gilbert syndrome 
New borns 
Hepatic damage

Question 30

Conditions that increase direct bilirubin ?

Answer 30

Bile duct obstruction
Dubin-Johnson ( defect in active transport proteins which transport conjugated bilirubin to the intestine )
Rotor syndrome
Hepatic damage

Question 31

What is Carbamoyl phosphate substrate for ?

Answer 31

1- for Ornithine transcarbamoylase in urea cycle to form citrulline
2- for Aspartate transcarbamoylase in pyrimidine synthesis

Question 32

Ttt of genetic deficiencies of Urea synthesis ?

Answer 32

Low protein diet
Lactulose
Sodium benzoate or Phenylpyruvate