Chapter 17 ( Amino Acid Metabolism ) Flashcards
Where does the 2 nitrogens of urea coming from ?
One from Aspartate and the other from Amino group which either comes from glutamine or glutamate
What is the major carrier of excess nitrogen from tissues ?
Glutamine
By what is kidney glutaminase induced ?
Chronic acidosis , in which excretion of ammonium may become the major defense mechanism
What does AST/ALT >1 indicate ?
Alcohol abuse
Carbamoyl phosphate synthase l ? Its obligate activator ?
Uses NH4 + HCO3 + 2 ATP to form carbamoyl phosphate
Obligate activator : N-acetylglutamate which produced only when free amino acids are present
Ornithine transcarbamoylase ?
Part of the urea cycle present in mitochondrial matrix
Transform Carbamoyl phosphate using ornithine into Citrulline
What does happen to aspartate in urea cycle ?
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
Similarities and differences between Carbamoyl phosphate synthase deficiency and Ornithine transcarbamoylase deficiency ? Ttt ?
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
Phenylketonuria defect ? Symptoms ? Screening ? Ttt ? Affected pregnant issues ?
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
Albinism defect ?
Tyrosinase enzyme deficiency which convert tyrosine to melanin
Alkaptonuria defect ? Symptoms ?
Defect : Homogentisate oxidase deficiency which leads to high levels of homogentisic acid in blood Symptoms : Dark urine Ochronosis ( black cartilage ) Arthritis
Maple syrup urine disease defect ? Symptoms ? Ttt ?
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
What substances is accumulating in propionyl CoA carboxylase deficiency ?
Propionic acid
Methyl citrate
Hydroxypropionic acid
What substances is accumulating in Methylmalonyl CoA mutase deficiency ?
Methylmalonic acid ( methylmalonic aciduria )
Homocystinemia defect ? Symptoms ? Diagnostic test ? Ttt ?
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
Difference between Marfan and homocystinemia in lens subluxation direction ?
Marfan : upward and outward
Homocystinemia : downward and inward
Important uses of SAM ? Its fate after donating the methyl group ?
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
Tetrahydrobiopterin (BH4) is necessary for which enzymes ? Regenerated by what ?
Tyrosine hydroxylase
Phenylalanine hydroxylase
Tryptophan hydroxylase ( serotonin synthesis )
Regenerated by dihydropetridine reductase
Vitamin B12 deficiency causes demyelination of what in the spinal cord ?
Posterior columns
Lateral corticospinal tracts
What are the heme proteins ?
Hemoglobin Myoglobin All the cytochromes Catalase Peroxidase Soluble guanylate cyclase
The rate limiting enzyme of heme synthesis ? Its inhibitor ? Activator ?
Sigma-aminolevulinate (ALA) synthase
Inhibitor : heme
Activator : Vit B6
Acute intermittent porphyria defect ? Mode of inheritance ? Symptoms ? Episodes induced by what ?
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
Porphyria cutanea tarda defect ? Mode of inheritance ? Symptoms ?
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
Mechanism of Barbiturates exacerbation of porphyria ?
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 .
