Biochemistry Flashcards
What 5 molecules are used to make purines?
Aspartate, glutamine, CO2, glycine, and THF
What 4 molecules are used to make pyrimidines?
Aspartate, glutamine, CO2, and ATP
In what order are the base, sugar-PRPP (ribose) assembled in:
Pyrimidines
Purines
Pyrimidines = Base + sugar-PRPP Purines = Sugar-PRPP + base
What is the rate-limiting step in pyrimidine and purine base synthesis?
Pyrimidine - CPS2
Purine - PRPP Synthetase
What is the mechanism of:
Hydroxyurea
5FU
Hydroxyurea = inhibits ribonucleotide reductase 5FU = inhibits thymidylate synthase
Megaloblastic anemia that is not corrected with vitB12 and folate supplementation
Orotic aciduria
Increased orotic acid in urine + hyperammonemia
Increased orotic acid in urine without hyperammonemia
Ornithine transcarbamylase deficiency
Orotic aciduria
Treatment for orotic aciduria
Uridine supplementation (bypass UMP synthase)
What is the mechanism of mycophenylate?
Inhibits IMP DH
What is the inheritance pattern of Lesch-Nyhan syndrome?
X-linked recessive
What DNA polymerases are used in prokaryotes and what are their functions?
DNApol1 = replaces primers DNApol3 = leading and lagging strand
What DNA polymerases are used in eukaryotes and what are their functions?
a - lAgging strand (has it’s own primase)
B - Mismatch DNA repair
d - leaDing strand
gamma - mitochondrial DNA replication
When is mismatch repair needed?
What disease results from a defect?
Wrong nucleotide is incorporated during replication Lynch syndrome (hereditary non-polyposis colorectal cancer HNPCC)
When is nucleotide excision repair needed?
What disease results from a defect?
When DNA is damaged outside of replication and causes bulky kinks (UV radiation causes thymidine dimers)
Xeroderma pigmentosum
When is base excision repair needed?
What type of DNApol is used?
When DNA is damaged outside of replication where the composition of the base is change but the backbone remains intact (non-bulky damage)
DNApol B
What are the steps of:
Nucleotide excision repair
Base excision repair
NER = endonuclease - DNApol - ligase BER = glycosylase (removes base from the backbone) - endonuclease - DNApol - ligase
When is non homologous end joining repair needed?
What disease results from a defect?
dander breaks
Ataxia-telangectasia
What is Bloom syndrome?
How does it present?
Defect in DNA helicase Sunlight hypersensitivity (similar to XP)
IgA deficiency + poor smooth pursuit/ataxia + spider angiomas + elevated AFP
Ataxia-telangectasia
What RNA polymerases are used in eukaryotes and what are their functions?
RNApol 1 = rRNA
RNApol 2 = mRNA
RNA pol 3 = tRNA
How is the a-amanitin toxin from the Amanita phalloides mushroom toxic?
Inhibits RNApol2 which impairs mRNA synthesis
I cell disease
Phosphotransferase mutation - cannot put mannose-6 phosphate on lysosomal enzymes to direct them, so they are released into the interstitial by default
Prader-WIlli syndrome
Maternal gene normally silenced, but paternal gene is also deleted - over eating, intellectual disability, hypogonadism, short stature
“POP” - praderwilli, over eating, paternal deletion
Angelman syndrome
Paternal gene normally silenced, but maternal gene is also deleted - inappropriate laughter (happy puppet), ataxia, seizures, intellectual disability
“MAMA” - maternal deletion, angelman, mood (laughter), ataxia
How do epinephrine (muscles) and glucagon (liver) raise blood sugar?
Bind GCPR (Gs type) - increase intracellular cAMP - activate protein kinase A - activate phosphorylase kinase:
- Inhibits glycogen synthase
- Activates glycogen phosphorylase
Hypoglycemia/hyperlipidemia + gout + elevated lactic acid + hepatosplenomegaly + enlarged kidneys
VonGierke disease (type 1) = glucose-6-phosphatase mutation Muscle doesn't release glucose into the blood, so this only affects liver (glycogenolysis and gluconeogenesis)
Hypoglycemia with normal lactic acid and uric acid + normal kidneys + hepatosplenomegaly + muscle weakness
Cori disease (type 3) = a-1,6-glucosidase mutation
Muscle cramps and myoglobinuria with strenuous exercise
McArdle disease (type 5) = glycogen phosphorylase
Where does glycogen accumulate in Pompe disease?
What organs are affected by infantile and adult type Pompe?
Lysosomes
Infant - cardiomyopathy
Adult - respiratory failure
What are the required co-factors for pyruvate DH?
B1 (thiamine), B2 (FAD), B3 (NAD), B5 (CoA), and lipoic acid
What 2 metabolites are elevated in pyruvate DH deficiency?
Lactic acid (lactic acid DH, pyruvate to lactic acid) and alanine (ALT, pyruvate to Ala)
What is the inheritance pattern for pyruvate DH deficiency?
How is it acquired?
X-linked Arsenic exposure (depletes lipoid acid and thiamine)
Treatment for pyruvate DH deficiency
Purely ketogenic protein and fat diet - Lysine and Leucine
What part of the electron transport chain is inhibited by: Rotenone (fish poison), MPTP/MPP Antimycin A (fish poison) CN, azide (N3-), CO, H2S Oligomycin (macrolide)
Complex 1
Complex 3
Complex 4
ATP synthase
What enzymes require Selenium?
Glutathione peroxidase and reductase
What enzyme is deficient in essential fructosuria?
Fructokinase
Hypoglycemia + hepatomegaly/jaundice
Fructose intolerance (fructose is trapped in the cells by phosphorylation, but cannot be utilized. Depleted PO4 shuts down gluconeogenesis and cannot correct hypoglycemia)
What enzyme is deficient in fructose intolerance?
What sugars must be avoided?
Aldolase B
Fructose or sucrose
Infantile cataracts and elevated galactose in urine/blood
Galactokinase deficiency - galactitol accumulates in the lens causing cataracts
Infantile cataracts + hepatomegaly/jaundice + intellectual disability
Classic galactosemia
What enzyme is deficient in classic galactosemia?
What sugars must be avoided?
Galactose-1-phosphate uridyltransferase
Galactose and lactose
How long is glycogenolysis used for fuel following a meal?
Only 2 hrs
What is used as fuel in starvation?
Glucose (hepatic gluconeogenesis) and FAs - 24 hrs
Ketone bodies - 48 hrs
What does the brain use as fuel in starvation? Muscles?
Brain - glucose then ketone bodies
Muscles - FAs
Intellectual disability + fair skin + eczema + seizures + musty body odor
Phenylketonuria - Phe hydroxylase or tetrahydobriopterin deficiency
Dark brown sclera + joint pain + urine turns black when exposed to air
Alkaptonuria = Homogentisate oxidase deficiency, homogentisic acid accumulation (toxic to cartilage)
Tall/kyphosis + intellectual disability + osteoporosis + downward lens subluxation + thrombosis
Homocysteinuria
Homocysteine accumulation damages endothelial cells, predisposing to thrombosis
What are 2 causes for homocysteinuria?
Cystathionine synthase dysfunction - deficiency or low affinity for vitB6
Homocysteine methyltransferase deficiency
Megaloblastic anemia + neurologic dysfunction (spinal cord demyelination) + normal methylmalonyl CoA
Homocysteinuria - homocysteine methyltransferase deficiency
Hexagonal cystine kidney stones
Cystinuria
What causes Cysteinuria?
How is it treated?
Defective transporter for Cys, Ornithine, Lys, and Arg (COLA) in renal proximal tubule and intestines
Acetazolamide - alkalinizes the urine = basic AAs lose their protons and become charged = increased solubility in the filtrate
Neutral aminoaciduria + pellagra
Hartnup disease
What is the most immediate source of nitrogen for the urea cycle?
Aspartate
What infection may require vitamin A supplementation?
Measles - prevents exfoliative rash
Hemolytic anemia + ataxia/peripheral neuropathy + proximal muscle weakness with a poor diet
Vitamin E deficiency
What 2 vitamins must be given to exclusively breast-fed babies?
Vitamin C and D
Scaly skin + hepatomegaly + joint pain + headaches
Vitamin A toxicity (causes pseudotumor cerebri = headaches)
What non-collagen enzyme requires vitamin C?
Dopamine B-hydroxylase (DA to NE)
What vitamin facilitates Fe absorption?
Vitamin C (keeps Fe in the reduced 2+ state)
Confusion + opthalmoplegia + ataxia + memory loss
Wernicke-korsakoff syndrome (thiamine deficiency)
What 2 other conditions are caused by thiamine deficiency?
Wet Beriberi - high output heart failure
Dry Beriberi - polyneuropathy
Angular chelitis + gossitis
Vit B2 (flavin) or B6 (PLP) deficiency vitB6 def will also have convulsions (required to make GABA)
What are 3 causes of pellagra (vitB3 niacin deficiency)?
Hartnup disease, carcinoid syndrome, and isoniazid
Indication for niacin therapy
Low HDL
What vitamin deficiency can lead to adrenal insufficiency?
Vitamin B6 (pantothenate, CoA - acetylCoA used to make cholesterol)
Which vitamin is a cofactor for the aminotransferases?
Vitamin B6 (pyridoxine, PLP)
What two vitamins are depleted by isoniazid?
Vitamin B3 (niacin) and B6 (PLP)
What 4 medications can cause folate deficiency?
Phenytoin, sulfonamides, MTX/TMP
What type of reaction converts methylmalonyl-CoA to saucily-CoA requiring vitaminB12?
Isomerization reaction (methylmalonyl-CoA mutase)
GI bleeding with late metabolic acidosis and GI obstruction (weeks later)
Fe poisoning (ROS generation causes the GI damage and scarring causes obstruction)
What enzymes require Zn?
Carbonic anhydrase and LDH
What type of patients should receive Zn supplementation?
Delayed wound healing
Impaire night vision + infertility + delayed wound healing + anosmia + acrodermatitis enteropathica
Zn deficiency
Wrist/foot drop + colicky abdominal pain + bright horizontal lines near long-bone metaphyses
Lead poisoning (lead lines = deposition of lead in growing bone) Also causes anemia and basophilic stippling
Treatment for lead poisoning
Succimer or EDTA
Severe = succimer + dimercaperol
What are 2 causes of acrodynia (peeling skin off the finger tips)?
Kawasaki disease and Hg poisoning
CNS changes + enlarged kidneys + history of eating large fish like swordfish or shark
Hg poisoning
What 4 conditions are associated with Down syndrome?
Duodenal atresia, endocardial cushion defects, ALL (“we ALL fall DOWN”), and alzheimer’s disease
What hematologic pathology is seen in newborns with Down syndrome?
Polycythemia
What are the 2 most common genetic causes for intellectual disability? What is the most common non-genetic cause?
Down syndrome then Fragile X syndrome
Fetal alcohol syndrome
What does the Quad screen look like in Down syndrome?
AFP, B-hCG, estriol, and inhibin A
AFP low, B-hCG high, estriol low, and inhibit A high
put in alphabetical order then start with down and alternate
What 3 congenital conditions will show nuchal translucency on 1st trimester ultrasound?
Down syndrome (trisomy 21), Patau syndrome (trisomy 13) and Turner syndrome
Micrognathia + clenched hands
Quad screen? (AFP, B-hCG, estriol, and inhibin A)
Edwards syndrome - trisomy 18 (Election age is 18 - Edwards)
AFP low, B-hCG low, estriol low, and inhibin A normal
Midline fascial defects/micropthalmia + polydactyly
What is used for prenatal detection?
Patau syndrome - trisomy 13 (Puberty at age 13 = Patau)
Decreased PAPP-A
What does FSH and LH look like in Klinefelters?
Abnormal seminiferous tubules = decreased Sertoli cell inhibin production = low FSH
Abnormal Leydig cells = decreased testosterone = low FSH
Tall + developmental delay + testicular atrophy
Klinefelter syndrome (47XXY)
High pitched cry/mewing in newborn
Cri-Du-Chat = “cry of the cat” (chr5 short arm deletion)
Elfin facies + extreme friendliness + hyperCa + intellectual disabiltiy
Williams Syndrome - increased sensitivity to vitD = hyperCa
“WILL ferrel in ELF movie”
Advanced paternal age is associated with what condition of the child?
What is the inheritance pattern?
Achondroplasia
Autosomal dominant FGFR3 mutation
Telangiectasia/AVMs throughout the body
Osler-Weber-Rendu (hereditary hemorrhagic telangiectasia)
What anemia is autosomal dominant?
Hereditary spherocytosis
What condition that predisposes to particular cancers is inherited in autosomal dominant pattern?
MEN
Intellectual disability + macroorchidism + mitral valve prolapse
Fragile X syndrome
What is the genetic cause of fragile X?
Trinucleotide repeat CGG
“Chromosome Girly-Girl = chr X”
Ataxia + hammer toes/pes cavus + hypertrophic cardiomyopathy + DM
Friedreich ataxia
What is the genetic cause of Friedreich ataxia?
Trinucleotide repeat GAA
“Gait Astoundingly Ataxic”
What antibiotic is used in CF that is not typically used in kids?
Fluoroquinolones
What condition is associated with gargoylism?
Hurler syndrome
What disorders are X-linked recessive?
“Oblivious Female Will Give Her Boys Her x-Linked Disorders”
Ocular albinism, Fabry disease, Wiscott-aldrich, G6PD deficiency, Hunter syndrome, Bruton agammaglobulinemia, Hemophilia A and B, Lesch-nyhan syndrome, and DMD
