Amino Acid/Nitrogen Flashcards
Argininemia
- description
- mechanism
- Treatment
- genetic hyperammonemia
- arginase defective –> arginine and ammonia buildup
- treat: low prot diet
Hyperammonemia
- description
- diagnostic signs
- treatment
- liver defect, acquired or genetic
- organic acid levels, AA, orotic acid in urine
- restrict protein diet, Na benzoate and Na phenylacetate
Arginosucciniaciduria
- descript
- mechanism
- diagnosis
- treatment
- genetic hyperammonemia
- defective AL –> ammonia buildup
- ammonia level in blood
- treat: hemodialysis, IV arginine delivery, restirct prot diet
Citrillinemia Type1
- mechanism
- symptoms
- mutation in AS gene –> ammonia accum in blood
- lethargy, seizures, ataxia
Citrullinemia type 2
- frequency
- mechanism
- east asians, middle E
- disfunction in citrin synthesis (transporter)–> ammonia buildup
Phenylketonuria (PKU)
- descript
- mechanism
- treatment
- tyrosine biosynthesis deficiency
- deficient phenylalanine hydroxylasee, dihydrobiopterin synthetase, dhydropteridine reductas –> excess phenylalanine –> phenylketo acids
- no diet food with phenylalalnine, take a tyrosine supplement (EAA now)
Tetrahydrobioterin deficiency
- description
- symptoms
- more severe form of PKU (tyrosine deficiency)
- loss of pigment, MR
Homocysteinuria
- description
- mechanism
- symptoms
- treatment
- recessive genetic; met metabolism deficiency
- CBS deficiency–> met excess, homocysteine excess
- homocysteine disrupts collagen linking –> atherosclerosis, PVD, ectopia lentis
- treat: restrict met diet, increase B6 (CBS needs PLP), B12 and folic acid supplement
Cystathioninuria
- description
- mechanism
- symptoms
- autosomal recesive; met metabolism disorder
- cystathionase deficiency –> excess cystathione
- benign; cys = EAA
Porphyrias
- descript
- symptoms
- [gly–>heme] deficiency –> metab intermediate accum
- cutaneous photosensitivity (reactive O2 species generated by sunlight); dark urine, darker under sunlight
Lead poisoning
- description
- mechanism
- symptoms
- [gly–>heme] deficiency
- ALA dehydratase and ferrochelatase block –> accum ALA in urea; IX accum in RBC
- neuro probs
GABA synthesis
glutamate decarboxylation
Histamine synthesis
histidine decarboxylation
5HT synthesis
hydroxytryptamine
Tryptophan –> decarboxylation –> 5HT
Epinephrine synthesis
tyrosine –> DOPA –> DA –> norepinphrine –> epinephrine
Carnitine synthesis
Lysine –> carnitine
NO synthesis
L-arginine +O2 –> CO + citrulline
Arsenic poisoning
- descript
- mechanism
- glycolysis/TCA
- arsenate decouples ATP synthesis
- arsenite binds pyruvate DH –>no acetyl CoA
- pyruvate excess –> lactic acidosis
Pyruvate kinase deficiency
-symptoms
glycolysis hemolytic anemia (dependent on glycolysis)
Pyruvate carboxylase deficiency
- mechanism
- symptoms
- types
- treatment
- TCA
- lactic acidosis; blocked gluconeogenesis –> hypoglycemia
- myelin impact
- A) infantile (NA); B) severe neonatal (france); C) mild intermittent
- avoid fast, high carb/high prot; citrate; biotin
Pyruvate dehydrogenase deficiency
- description
- types
- treatment
TCA
- xlinked; lactic acidosis
- metabolic form (severe) (death at birth from LA); chronic neurological form (mild) MR
- high fat/low carb; thiamin supplement
Acute cyanide poisoning
- mechanism
- symptoms
- treatment
Oxphos
- binds Fe3+ of cytochrome oxidase
- hyperventilation, lactic acidosis
- treat: nitrite (oxidizes hb, will bind here)
MERFF
- mechanism
- symptoms
- treat
mitochondrial DNA mutations; Oxphos
- point mutation at mt tRNA
- epilepsy, dementia
- treat: coE Q10, carnitine
LHON
- mechanism
- symptom
(lebers hereditary optic neuropathy) mt DNA mutation; oxphos
- complex I mutation (NADH Q reductase)
- optic nerve degen
Leigh syndrome
- mechanism
- symptom
- mt DNA mutation; oxphos
- complex I, IV mutation (also X linked form)
- neurodegen (death within 2 yrs)
Leigh syndrome is also know as?
Subacute necrotizing encephalopathy
MCAD deficiency:
- mechanism
- symptom
- treatment
FA beta oxidation
- acyl CoA DH defect –> MCFA accum
- hypokinetic hypoglycemia
- treat: high carb/low fat; avoid fast
What disease is associated with SIDS?
MCAD deficiency
CPT II deficiency
- symptom
- types
- treatment
Carnitine metab; FA oxidation
- myoglobinuria w exercise/fast
- adult, infantile, neonatal (lethal)
- treat: avoid fast/exercise/fat; more SCFA intake, carnitine supplement
Jamaican Vomiting Sickness
- symptom
- mechanism
Carnitine metabolism; FA oxidation
- inhibit SCAD and MCAD –> SCFA and MCFA buildup –> dicarboxylic acid in urine
- severe hypoglycemia
Proprionic acidemia
- mechnism
- smptoms
- treatment
Odd chain oxidation
- defect [proprionyl CoA–> methylmalonyl CoA] –> excess proprionyl CoA
- acidic urine, ketoacidosis, hypoglycemia, hyperammonemia
- treat w bicarb, decrease prot/high carb
Methylmalonic acidemia
- mechanism
- symptom
- treatment
Odd chain
- defect MCM or B12 deficiency
- methylmalonic acid in urine, hypoglycemia, hyperammonemia
- treat: low AA, low odd chain, B12 supplement, carnitine supplement
Methylmalonic acidemia can be caused by what vit deficiency?
B12
Zellweger spectrum disorders
- descript
- types
peroxisoomal FA oxidation
- defect peroxisome biogenesis
- zellweger syndrome (most severe); neonatal adrenoleukodystrophy (NALD); infantil refsum disease (IRD) (loss of sense and motor progressive)
Refsum disease
- types
- symptoms
- treatment
Peroxisomal FA oxidation
- Type 1: PAHX defect; Type 2: peroxin 7 defect
- retinosa pigmentosa, other sensory prob
- treat: diet restrict; avoid phytanic acid (cows)
X-linked adrenoluekodystrophy
- mechanism
- symptom
- types
- treatment
peroxisomal FA oxidation
- protein that transports VLCFA to peroxisome
- myelin damage
- childhood cerebral ALD (Severe death 2 yrs), adrenomyeloneuropahty (AMN) progressive)
- lorenzos oil
Foldase enzymes (2)
PPI: speeds cis –> trans isomerization
PDI: speeds oxidation (in ER)
Lissencephaly
missense mutation (incomplete folding of tubulin0 –> defective nueron migration
Alpha antitrypsin deficiency
protease LOF (incomplete folding ) --> aggregation GOF lung liver damage
