UWorld 2017 Flashcards by Melissa Khalil

Methylmalonic acidemia

Deficiency of methylmalonyl-CoA mutase
Lethargy, tachypnea, vomiting (newborn)
Hyperammonemia, ketotic hypoglycemia, metabolic acidosis
Urine: elevated methylmalonic acid + propionic acid

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Fabry disease

Alpha-galactosidase A deficiency
Accumulation of globotriaosylceramide
Early: neuropathic pain, angiokeratomas
In adulthood: proteinuria, renal failure, ventricular hypertrophy, transient ischemic attack, stroke

How well did you know this?

Not at all

Perfectly

Lead toxicity

Inhibition of ferrochelatase + D-ALA dehydratase
Anemia, ALA accumulation, high zinc protoporphyrin
Neurotoxicity (long-terme)

How well did you know this?

Not at all

Perfectly

Fragile X syndrome

Often w/ developmental delay + neuropsychiatric findings

Anxiety disorders, autism, ADHD

How well did you know this?

Not at all

Perfectly

Adhesin of cells to extracellular matrix

Integrin binding to fibronectin / collagen / laminin

Differential expression of integrin subtypes correlates w/ malignant behavior (ex: melanoma)

How well did you know this?

Not at all

Perfectly

Base excision repair

Correct single-base DNA defects

By glycosylase - endonuclease + lyase - polymerase - ligase

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Impaired tetrahydrobiopterin (BH4)

Esp by DH4 reductase deficiency

Account for 2% of phenylcetonuria

How well did you know this?

Not at all

Perfectly

Vitamin A overuse

Intracranial HTN
Skin changes
Hepatosplenomegaly

How well did you know this?

Not at all

Perfectly

Regulation of Ras-MAPK signal transduction

Balance: Ras protein GTP-bound (active) + GDP-bound (inactive)
RAS gene mutation: activated Ras protein (dev of cancer)

How well did you know this?

Not at all

Perfectly

DNA polymerase I function in prokaryotes

5’ to 3’ exonuclease: removes RNA primase + repair damaged DNA
3’ to 5’ exonuclease
5’ to 3’ polymerase

How well did you know this?

Not at all

Perfectly

RBC’s inability to synthesize heme

If mitochondrial loss

Mito necessary for first + final 3 steps of heme synthesis

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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