UWorld 2017 Flashcards
Methylmalonic acidemia
Deficiency of methylmalonyl-CoA mutase
Lethargy, tachypnea, vomiting (newborn)
Hyperammonemia, ketotic hypoglycemia, metabolic acidosis
Urine: elevated methylmalonic acid + propionic acid
5 precursors of Propionyl-CoA + 4 symptoms of propionyl acidemia
Valine, isoleucine, methionine, threonine, odd-chain fatty acids
Lethargy, vomiting, poor feeding, hypotonia (1-2w after birth)
Classic galactosemia
Galactose-1-phosphate uridyl transferase (GALT) deficiency
Few days after breastfeeding
Vomiting, lethargy, jaundice, hepatomegaly, renal dysfunction, E coli sepsis
Ttt: cessation of breastfeeding + switching to soy milk-based formula
Fabry disease
Alpha-galactosidase A deficiency
Accumulation of globotriaosylceramide
Early: neuropathic pain, angiokeratomas
In adulthood: proteinuria, renal failure, ventricular hypertrophy, transient ischemic attack, stroke
Lead toxicity
Inhibition of ferrochelatase + D-ALA dehydratase
Anemia, ALA accumulation, high zinc protoporphyrin
Neurotoxicity (long-terme)
Fragile X syndrome
Often w/ developmental delay + neuropsychiatric findings
Anxiety disorders, autism, ADHD
Adhesin of cells to extracellular matrix
Integrin binding to fibronectin / collagen / laminin
Differential expression of integrin subtypes correlates w/ malignant behavior (ex: melanoma)
Base excision repair
Correct single-base DNA defects
By glycosylase - endonuclease + lyase - polymerase - ligase
Vitamin B12 deficiency
Megaloblastic anemia (impaired DNA synthesis) Neurologic def (impaired myelin synthesis): subacute combined degeneration of dorsal columns + lat corticospinal tract High methylmalonic acid + homocysteine
Impaired tetrahydrobiopterin (BH4)
Esp by DH4 reductase deficiency
Account for 2% of phenylcetonuria
Vitamin A overuse
Intracranial HTN
Skin changes
Hepatosplenomegaly
Regulation of Ras-MAPK signal transduction
Balance: Ras protein GTP-bound (active) + GDP-bound (inactive)
RAS gene mutation: activated Ras protein (dev of cancer)
DNA polymerase I function in prokaryotes
5’ to 3’ exonuclease: removes RNA primase + repair damaged DNA
3’ to 5’ exonuclease
5’ to 3’ polymerase
RBC’s inability to synthesize heme
If mitochondrial loss
Mito necessary for first + final 3 steps of heme synthesis
Alkaptonuria
Lack of homogentisic acid dioxygenase Blocking metab of tyrosine Accumulation of homogentisic acid Black urine when exposed to air Blue-black pigm on face Ochronotic arthropathy
microRNA + siRNA
Short non-coding RNA sequences
Base-pairing w/ complementary sequences in mRNA
Induce posttranscriptional gene silencing
Hartnup disease
Impaired transport of neutral aa
Niacin deficiency
Pellagra-like skin eruptions, cerebellar ataxia
Dg: excessive neutral aa in urine
Principal stabilizing force of secondary structure of proteins
Hydrogen bonds
Synchronization of glycogen degradation w/ skeletal muscle contraction
Due to release of sarcoplasmic Ca2+
Increased intracellular Ca2+: activation of phosphorylase kinase, stimulation of glycogen phosphorylase, increased glycogenolysis
Pompe disease
Acid maltase (alpha-glucosidase) deficiency
Abnl glycogen accumulation in lysosomes of muscles
Early infancy
Cardiomegaly, macroglossia, profound muscular hypotonia
Congenital def of propionyl-CoA carboxylase
Enzyme converts propionyl-CoA to methylmalonyl-CoA
Propionyl-CoA from metab of valine, isoleucine, methionine, threonine, odd-chain fatty acids
Enz def: propionic acidemia - lethargy, poor feeding, vomiting, hypotonia (1-2w after birth)
Hepatic encephalopathy
Hyperammonemia in adv liver failure
Ammonia crosses BBB: excess glutamine accumulate in astrocytes
Decreased glutamine for conversion to glutamate in neurons: disruption of excitatory neurotransmission
Cause of diff clinical severity betw/ HbS and HbC
HbS: valine in place of glutamic acid
Hydrophobic interaction in Hb + HbS polymerization (sickling)
Increased Fructose 2,6-biphosphate in hepatocytes
Inhibit conversion of Alanine to glucose
F2,6BP activates PFK-1 (increased glycolysis) + inhibits fructose 1,6-biphosphatase (decreasing gluconeogenesis)
Insulin activates phosphofructokinase-2 that increases F2,6BP
Glucagon activates fructose 2,6-biphosphatase that decreases F2,6BP
Pentose phosphate pathway
Oxidative (irreversible) + nonoxidative (reversible)
Transketolase: for interconversion of ribose-5-phosphate and fructose-6-phosphate
3’ CCA tail of tRNA
Is amino acid binding site
Aminoacyl tRNA synthetase: for loading the appropriate aa to 3’CCA tail
Abetalipoproteinemia
Inability to synthesize apolipopB
Lipids absorbed but not transported into blood
Accumulate in intest epith = enterocytes + clear/foamy cytoplasm
Phenylketonuria
Phenylalanine hydroxylase deficiency
Tetrahydrobiopterin defiency
Accumulation of phenylalanine in body fluids + CNS
Homozygous: normal at birth then severe intellect disability+seizures
Hipopigm: skin, hair, eyes, catechol brain nuclei (substantia nigra, locus ceruleus, vagal nucleus dorsalis)
Chronic thiamine deficiency
Decreased activity of enzymes w/ B1 cofactor
Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase
Impaired glucose utilization in CNS
B1 def dg if erythrocyte transketolase activity is low and increases after addition of thiamine pyrophosphate
GALT vs GALK deficiencies
GALT def: accumulation of galactose-1-phosphate, neonatal presentation, vomiting, lethargy, failure to thrive, hepatic+renal dysfct
GALK: galactose accumulation, late presentation, normal growth, CATARACT (galactitol accum)
lac operon regulation
Negatively: binding of repressor prot to operator locus
Positively: cAMP-CAP binding upstream from promoter
Expression of lac operon: mutations that impair binding of repressor prot (Lac I) to its regulatory sequence in operator region
Vitamin E deficiency
Vit E protect fatty acids from oxidation
Vit E def (when fat malabsorption): oxidative injury of cell membranes, esp neurons w/ long axons + erythrocytes
Vit E def manif: neuromusc ds (ataxia, impaired proprioception + vibratory sensation), hemolytic anemia
Riboflavin
Precursor of coenzymes FMN, FAD
FAD participates in tricarboxylic acid cycle + electron transport chain
FAD acts as electron acceptor for succinate dehydrogenase (complex II) that converts succinate into fumarate
Retinoblastoma protein phosphorylation
By proliferation signals that activate CDK4
Increases DHF reductase and DNA polymerase activity
Hyperphosphorylated Rb is inactive: cells transition unchecked from G1 to S phase
Minor cause of Down sd
Unbalanced Robertsonian translocation
2 acrocentric nonhomologus chrom
46, XX or XY, t(14;21)
CFTR protein in cystic fibrosis
Mutation: DF508, prot misfolding
Failure of glycosylation
Proteasome-mediated degradation
Decreased nb of transmembrane CFTR prot
Elastin
Extensive cross-linking between monomers
Facilitated by lysyl oxidase
Alpha1-antitrypsin def: early lower lobe emphysema (excessive elastin degradation)
Chronic granulomatous ds
Mutation in NADPH oxidase
Neutro cant form oxidative burst (kill org in phagolysos)
Dg: absence normal blue by nitroblue tetrazolium test + absence fluo green by dihydrorhodamine flow cytometry test
High risk in X-linked agammaglobulinemia
Absence of opsonizing/neuralizing Ab: pyogenic bact, enteroviruses, Giardia lamblia
