Biochemistry Flashcards
Fabry dz
XLR; alpha-galactosidase; ceramide trihexoside; pw painful neuropathy, angiokeratomas, hypohydrosis; will develop progressive renal failure
Gauncher dz
AR; beta-glucocerebrosidase; glucocerebroside; gaucher cells (“crumpled tissue paper” macrophages), HSM, pancytopenia, severe bone and joint pain
Hurlur syndrome
AR; alpha-L-iduronidase; dermatan and heparan sulfate; gargoylism, developmental delay, corneal clouding, HSM
Hunter syndrome
XLR; iduronate sulfatase; dermatan and heparan sulfate; similar to, but milder than, Hurlur syndrome (no corneal clouding however)
Niemann-Pick dz
AR; sphingomyelinase; sphingomyelin; HSM, cherry-red spot in macula, foam cells, progressive neurodegeneration
TaySachs
AR; beta-hexosaminidase; Gm2 ganglioside; cherry-red spot in macula, progressive neurodegeneration, no HSM
Krabbe dz
AR; galactocerebrosidase; galactosylspingosine & galactocerebroside; progressive neurodegeneration, optic atrophy
Metachromatic leukodystrophy
AR; arylsulfatase A; cerebroside sulfate; muscle wasting, dementia, ataxia
Histones: AA?
lysine, arginine
In DNA methylation, which nucleotides are methylated?
cytosine and adenine
DNA methylation of what sequence represses transcription?
CpG islands
Histone methylation makes DNA what?
Mute
Histone acetylation makes DNA what?
Active
Uracil: made from what nucleotide, replaces what in RNA
Cytosine, thymine
Why does increased G-C content increase the melting temperature of DNA?
3 H bonds over 2
AA needed for purine synthesis (GAG)
Glycine, aspartate, glutamine
Adenosine deaminase deficiency MOA
Excess ATP and dATP imbalances nucleotide pool, prevent DNA synthesis and reduces lymphocyte count (cause autosomal recessive SCID)
Lesch-Nyhan syndrome MOA, pw
absent HGPRT leads to defective purine salvage (normally converts hypoxanthine to IMP and guanine to GMP). results in excess uric acid production and de novo purine synthesis; Hyperuricemia, Gout, Pissed off, Retardation, dysTonia
AUG
Methionine in eukoaryotes; fMet in prokaryotes (stimulates PMN chemotaxis)
non-degenerate AA
methionin (AUG), tryptophan (UGG)
DNA polymerase III
prokaryotic only; proofreads with 3’-5’ exonuclease
DNA polymerase I
degrades RNA primer and replaces it with DNA (5’-3’ exonuclease)
DNA ligase
catalyze the formation of phosphodiester bond within a strand of dsDNA (okazaki fragments)
telomerase
RNA-dependent DNA polymerase that adds DNA to 3’ ends of chromosomes to avoid loss of genetic material with every duplications, eukaryotes only
silent mutations often occur
3rd position of codon (tRNA wobble)
missense mutations example
sickle cell dz (substitution of glutamic acid with valine)
nonsense mutation
stop the nonsense!
frameshit mutation example
duchenne muscular dystrophy
nucleotide excision repair occurs when, moa, and defect
G1; endonucleases release damaged bases (esp during UV exposure), DNA polymerase/ligase reseal gap; xerderma pigmentosum
base excision repair occurs when, moa
occurs throughout cell cycle; base-specific glycosylase removes altered base and creates AP site, with AP-endonuclease cleaving 5’ end and lyase cleaving 3’ end; DNA polymerase-beta fill s gap and DNA ligase seals it
mismatch repair occurs when, moa, and defect
G2; mismatched nucleotides on newly synthesized strand are removed and fixed; defective in HNPCC
nonhomologous end joining moa, defect
repairs double-stranded breaks, no homology requirements; mutated in ataxia telangiectasia, fanconi anemia
protein synthesis direction
N to C terminus
DNA replication inhibiting drugs have what modification that prevents addition?
Modified 3’OH that prevents addition of the next nucleotide
mRNA stop codons
UGA, UAG, UAA
RNA polymerase I, II (opens up DNA at promoter site), III
rRNA (rampant), mRNA (massive), and tRNA (tiny)
alpha-amanitin (amanita phalloides) effects which
RNA polymerase II
hnRNA to mRNA transition
5’ capping (7-methyl guanosine cap), 3’ polyadenylation, and intron splicing
mRNA quality control occurs where?
cytoplasmic P-bodies (exonucleases, decapping enzymes, microRNAs)
SLE pts have antibodies to what structure?
anti-smith (spliceosomal snRNP)
MCTD pts have antibodies to what structure?
Anti-U1 RNP
Labile cells
BM, gut epithelium, skim, hair follicles, germ cells
What cells are rich in RER?
goblet cells, plasma cells
What cells are rich in SER?
Liver hepatocytes (detoxification of drugs and poisons), and adrenal cortex (steroid synthesis)
Golgi adds which molecule to proteins to signal movement to lysosome?
mannose-6-phosphate
inclusion cell disease
defect in N-acetylglucosaminyl-1-phosphotransferase, golgi fails to phosphorylate mannose residues to proteins, sending proteins extracellular as opposed to lysosomes. pw coarse facial features, clouded corneas, restrictd joint movement, and high plasma levels of lysosomal enzymes
signal recognition particle
cytosolic ribonucleoprotein that traffics protein from the ribosome to the RER
COPII
anterograde transport: ER - Golgi
COPI
retrograde transport: golgi - ER
clathrin
trans-golgi to lysosomes; plasma membrane to endosome (receptor -mediated endocytosis)
Peroxisome
catabolism of very-LC FA, branched-chain FA, AA
Defects in ubiquitin-proteasome system implicated in what disease
Parkinson
Type I collagen
Bone, skin, tendon, teeth (decreased production in osteogenesis imperfecta)
Type II collagen
Cartilage
Type III collagen
reticulin (blood vessels, skin, uterus)
Type IV collagen
basement membrane (defective in alport, targeted by antibodies in goodpasture syndrome)
Menkes dz MOA
XLR CT dz caused by impaired copper absorption and transport due to defective Menkes protin; decreased activity of lysyl oxidase (as Cu is an essential cofactor); leads to brittle, kinky hair, growth retardation, and hypotonia
elastin is rich in what?
nonhydroxylated glycine, proline, and lysine
marfan syndrome
defect in fibrillin, a glycoprotein that forms a sheath around elastin
Cre-lox system
inducibly manipulate genes at specific development points (e.g. to study a gene whose deletion causes embryonic death)
RNA interference
dsRNA complementary to mRNA sequence of interest is transfected into human cells, where it separates and promots degradation of target mRNA, knocking down gene expression
Hardy weinberg assumptions
no mutations, no natural selection, random mating, and no net migration
Prader-willi moa
deletion on c15 (paternal); results in hyperphagia, obesity, hypogonadism, hypotonia, and intellectual disability
angelman moa
deletion on c15 (maternal); results in inappropriate laughter, seizures, ataxia, severe intellectual disability
X-linkd dominant example
Hypophosophatemic rickets: increased phosphate wasting at proximal tubule, results in rickets-like presentation
mitochondrial inheritance example
miochondrial myopathies; pw myopathy, lactic acidosis, and CNS dz; 2/2 failure in oxidative phosphorylation, and muscle biopsy shows “ragged red fibers”
ADPKD mutation
85 percent: PKD1 on c16; 15 percent: PKD2 on c4
FAP mutation
APC gene on c5q (5 letters on polyp)
familial hypercholesterolemia
absent LDL receptor leads to elevated LDL, leads to athersclerotic dz, corneal arcus, tendon xanthomas
hereditary hemorrhagic telangiectasia
inherited disorder of blood vessels; pw telangiectasia, epistaxis, AVM, Gi bleeding, hematuria
huntington dz
caudate atrophy; CAG repeat on gene 4 (hunting 4 food)
li-fraumeni mutation
TP53 mutation leads to multiple malignancies at early age
marfan mutation
FBN1 gene mutation on c15 ; cystic medial necrosis of the aorta leads to aortic incompetence and dissections, floppy MV
NF1 mutation
NF1 gene on c17
NF2 mutation
NF2 gene on c22
VHL dz
deletion of VHL gene on c3 (3 words for chromosome 3)
duchenne: common cause of death
dcm
dystrophin function
largest protein-coding gene; in skeletal and cardiac muscle, connects intracellular cytoskeleton with transmembrane protein alpha and beta dystroglycan, which are connected to the ECM. loss of dystrophin leads to myonecrosis.
myotonic type 1 mutation, presentation
CTG repeat on DMPK gene, abnormal expression of myotonin protein kinase; pw myotonia, testicular atrophy, frontal balding, and arrhythmia
fragile x syndrome mutation, presentation
x-linked defect of the FMR1 gene, trinucleotide repeat disorder CGG; pw eXtra large tests, jaws, ears
T21: first-trimester US, serum findings
increased nuchal translucency, hypoplastic nasal bone; decreased PAPP-A, increased free beta-hCG
T21: other findings
duodenal atresia, hirschsprung dz, atrial septal defect, early-onset alzheimer (c21 codes for amyloid)
t18: serum lab findings
decreased papp-a, decreased estriol, decreased beta-hCG, decreased inhibin A
cri-du-chat mutation, pw
short arm, c5, severe intellectual disability, high-pitched crying/mewing
williams syndrome mutation, pw
long arm, c7; pw elfin faces, extreme friendliness with strangers, intellectual disability, hypercalcemia
CATCH-22
velocardiofacial syndrome (Cleft palate, abnormal facies); diGeorge syndrome (thymic aplasia, cardiac defects, hypocalcemia)
vita A function, deficiency, excess
essential for normal differentiation of epithelial cells into specialised tissue (pancreatic cells, mucus-producing cells), constituent of visual pigments; used to treat measles, AML, and acne/wrinkles
vita A deficiency
night blindness, dry skin, immunosuppression;
vita A toxicity
acute: N/V, blurred vision, vertigo, chronic: pseudotumor cerebri, dry skin/alopecia, hepatic toxicity, arthralgias; teratogenic (cleft palate, heart abnormalities)
b1/thiamine fxn, dx
cofactor for dehydrogenase enzyme rxn: ATP=alpha-ketoglutarate dehydrogenase, transketolase, pyruvate dehydrogenase); increase in RBC transketolase activity after B1 administration
b1/thiamin deficiency
impaired glucose breakdown, affects highly aerobic tissues (brain, heart) first; wenicke-korsakoff syndrome, dry beriberi (polyneuritis, symmetrical muscle wasting), wet beriberi (hig-output cardiac failure, edema)
b2/riboflavin fxn, deficiency
cofactors in redox reactions (FAD, FMN); cheilosis, corneal vascularization
b3/niacin fxn, indications
synthesized from b2+b6; cofactors in redox reactions (NAD, NADP), derived from tryptophan, used to treat dyslipidemia (lowers VLDL, raises HDL)
b3/niacin deficiency
glossitis; pellagra (diarrhea, dementia, dermatitis - “broad collar” rash) in hartnup dz (decreased tryptophan absorption), malignant carcinoid syndrome, isoniazid (decreased b6)
b5/pantothenic acid fxn, deficiency
Component of coenzyme A, FA synthase; dermatitis, enteritis, alopecia, adrenal insufficiency
b6/pyridoxine fxn
converted to PLP, a cofactor in transamination, decarboxylation reactions, and glycogen phosphrylase; synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters
b6/pyridoxine deficiency
convulsions, hyperirritability, peripheral neuropathy (induced by isoniazid, OCP), sideroblastic anemia 2/2 impaired hemoglobin synthesis and Fe excess
b7/biotin fxn, deficiency
cofactor for carboxylation enzymes, dermatitis, alopecia, enteritis caused by excess ingestion of raw egg whites
b9/folate fxn
converted to THF, a coenzyme for methylation reactions,impt for synthesis of nitrogenous bases in DNA/RNA; found in leafy green vegetables, absorbed in jejunum
b9/folate deficiency
m/c vitamin deficiency (esp in etoh and pregnancy), can be caused by phenytoin, sulfonamides, MTX, megaloblastic anemia, glossitis, increased homocysteine, NT defects
b12/cobalamin fxn
cofactor for homocysteine methyltransferase, methylmalonyl-coa mutase, found in animal products, very large reserve pool (4 years) stored in liver`
b12/cobalamin deficiency
insufficient intake (veganism), malabsorption, lack of intrinsic factor (pernicious anemia, gastric bypsas), absence of terminal ileum (CD); megaloblastic anemia, subacute combined degeneration), increased homocysteine and methylmalonic acid; prolonged deficiency leads to irreversible nerve damage
vita C fxn
facilitates Fe absorption by reducing it to Fe2+ state, necessary for hydroxylation of profline/lysine in collagen synthesis, necessary for dopamine beta-hydrxylase (converts DA to NE)
vita C deficiency, excess
scurvy (swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, subperiosteal hemorrhages); N/V, diarrhea, Ca oxalate nephrolithiasis, can increase risk of Fe toxicity in predisposed individuals (transfusions, hereditary hemochromatosis)
vita E fxn, deficiency
antioxidant (protects RBCs, membranes from free radical dmg); hemolytic anemia, posterior column and spincerebellar tract demyelination
vita K fxn, deficiency
cofactor for gamma-carboxylation of glutamine acid residues on blood clotting proteins, synthesized by intestinal flora; increase PT, aPTT with normal bleeding time, occurs in infants or after prolonged periods of antibiotic used (esp liver dz, malabsorption syndromes)
zinc deficiency
acrodermatitis enteropathica, delayed wound healing, anosmia/dysgeusia, hypogonadism, decreased adult hair
Kwashiorkor (MEAL)
protein malnutrition leads to edema, anemia, liver (fatty)
Glucogenic essential AA
methionine, valine, histidine
Ketogenic essential AA
leucine, lysine
Acid AA
glutamic acid, aspartic acid
Basic AA
arginine, lysine, histadine (arg/lys in histones; arg/his during growth)
Ammonia intoxication
asterixis, slurring of speech, somnolence, vomiting, cerebral edema, vision blurring
Tryptophan products
Niacin then NAD/NADP (requires B6), serotonin then melatonin (b4,b6)
Histidine product
Histamine (B6)
Glycine product
Porphyrin (B6) then heme
Glutamate products
GABA (B6), glutathione
Arginine products
Creatinine, urea, NO (requires B4)
PKU moa, pw, rx
Decreased phenylalanine hydroxylase or BH4, tyrosine because essential; intellectual disability, growth retardation, seizures, fair skin, musty body odor; decrease phenylalanine and increase tyrosine/BH4 intake (must avoid artificial sweetener aspartame)
Maternal PKU moa, pw
lack of dietary therapy for PKU pts in pregnancy; intellectual disability, growht retardation, microscephaly, heart defects
maple syrup urine moa, pw, rx
decreased alpha-ketoacid dehydrogenase (B1) impairs degradation of branched AA (isoleucine, leucine, valine); increased alpha-ketoacids in the blood, pw severe CNS defect, intellectual disability, death; restriction of branched AA in diet, thiamine supplementation
alkaptonuria moa, pw, rx
congenital deficiency of homogentisate oxidase in tyrosine degradation pathway; pw pigment forming homogentisic acid accumulates in tissue (dark connective tissue, brown sclerae, urine turns black, debilitating arthralgies)
Homocystinuria pw
marfanoid habitus, kyphosis, lens subluxation, intellectual disability, increased homocysteine in urine, thrombosis, athersclerosis (stroke, MI)
Cystinuria moa, pw, rx
defect of renal PCT and intestinal AA transporter that prevents reabsorption of COLA (cysteine, ornithine, lysine, arginine), leads to recurrent precipitation of hexagonal cysteine stones; urinary aklalinzation (with K citrate, acetazolamide), chelating agents (penicillame), and hydration
glycogen storage disease: all types
Von gierke; pompe; cori; mcardle dz (very poor carbohydrate metabolism); all AR
Von Gierke disease (type 1)
Glucose 6 phosphatase deficiency; pw severe fasting hypoglycemia, increased lactate, triglycerides, uric acid, hepatomegaly 2/2 glycogen storage in liver
pompe disease (type 2)
lysosomal alpha-1,4-glucosidase (acid maltase) deficiency; cardiomegaly, hypertrophic cardiomyopathy, glycogen accumulatoin in lysosomes, normal blood sugar levels
cori disease (type 3)
alpha-1,6,glucosidase deficiency; pw milder form of type 1 with normal blood lactate levels; gluconeogenesis intact
mcardle disease (type 4)
SK glycogen phosphorylase; increased glycogen in muscle that it cannot break down, leads to painful muscle cramps, myoglobinuria with exercise, and arrhythmia from electrolyte abnormalities; rx with vitamin B6
leptin moa and effect
acts on arcuate nucleus of hypothalamus to inhibit production of neuropeptide Y (appetite stimulant) and stimulate production of alpha-MSH (promote satiety)
Why do bruises turn green?
heme oxygenase converts heme to biliverdin, which is green
HbS protein defect
At position 6 of the beta subunit, valine replaces glutamic acid. This promotes hydrophobic interaction among hemoglobin molecules and results in polymerization (during hypoxia, increased acidity, low blood volume)
HbC protein defect
At position 6 of the beta subnit, lysine replaces gluatmic acid. lysine does not induce sickling because it itself is charged (like glutamic acid), and results in chronic hemolytic anemia
Pigmented gallstone moa
infection of gallbladder release beta-glucuronidase from bacteria (e.coli. ascaris lumbricoides), contributes to the hydrolysis of bilirubin glucouronides and increase amount of unconjugated bilirubin in bile
chronic myeloproliferative disorder mutation, moa, presentation
mutation (V617F) in cytoplasmic tyrosine kinase (JAK2), which results in constitutive tyrosine kinase activity and cytokine-independent activation of STAT transcription factors
pyruvate dehydrogenase deficiency moa, diet supplementation
Prevent conversion of pyruvate to acetyl-CoA, thus shunting pyruvate to LA; rx with lysine and leucine (exclusively ketogenic)
nitrate deaminates cytosine, adenine, gluanine to form?
uracil, xanthine, hypoxanthine
how to fix cytosine deamination?
base excision repair: glycosylase recognizes, cleaves altered DNA bases, creating AP site; endonuclease cleaves 5’ end and lyase cleaves 3’ sugar phosphate; and DNA polymerase and ligase reform!
DNA dmg mechanism and repair mechanisms
depurination of DNA (base excision repair); UV induced formation of thymin dimers; ionizing radiatoin induced breaks in DNA chains; chemical agent induced cross-linkage, intercalation, alkylation
Elevated argining levels in pt with spastic paresis in LE and choroeoathetoid movements
Arginase deficiency (typically produces urea and ornithine)
glutamine is the major AA in blood because
it transports ammonia from peripheral tissues to the kidney
b12 deficiency takes how long to manifest?
many years (4)
amatoxin (rom poisonous mushrooms) inhibit what structure?
RNA polymerase II (halting mRNA synthesis)
Acceptor stem and aminoacylation
Base pairing of 5’ and 3’ terminal nucleotides; CCA tail hangs off 3’ end where the AA binds to the 3’ terminal hydroxyl group; aminoacylation catalyzed by aminoacyl tRNA synthetsae
D arm consists of, fxn
dihydrouracil residues; facilitates correct tRNA recogniition by proper aminoacyl tRNA synthestase
T arm consists of
thymidine (only RNA species that contains thymidine instead of uracil), pseudouridine, cytidine
Arginine + aspartate
urea
glycine + succinyl CoA
heme
glycine + arginine + SAM
creatinine
glutamate products
GABA, glutathione
glutamate + aspartate
pyrimidines
glutamate + aspartate + glycine
purine
histidine
histamine
tyrosine
thyroxine, melanin
stimuli for vasodilation of vascular endothelium
acetylcholine, shear forces, bradykinin, serotonin, substance P
enzyme that synthesizes NO
eNOS (activated by Ca)
NO moa at smooth muscle cell
Activates GC, increases cGMP production, activate protein kinase G, reduce cytosolic Ca levels and relax SMC
riboflavin deficiency (3 functions)
FMN/FAD impt cofactors for flavoproteins (enzymes for redox); form complex I (FMN), complex II (FAD) in electron transport chain; and FAD is a cofactor for succinate dehydrogenase (converts succinate to fumarate in TCA cycle)
16S rRNA sequence fxn
locatedon 30S unit, complementary to Shine-Dalgarno sequence on mRNA, binding is necessary for initiation of protein translation
beta thalassemia moa
m/c aberrant splicing of precursor mRNA or premature chain termination during mRNA translation
Signs specific to Fe deficiency
dysphagia (2/2 esophageal webs) and disfigured fingernails
duodenal enteropeptidase fxn
activate trypsinogen to trypsin, necessary for protein digestion and absorption via 2 mechanisms (degrades complex peptides to dipeptides/AA, activates othe rproteases such as carboxypeptidase, elastase, chymotrypsin)
lipase fxn
digestion of triglycerisdes
pancreatic amylase fxn
hydrolysis of complex carbohydrates to oligo, di, monosaccharides
myoglobin
monomeric, primary oxygen-storing protien in skeletal and cardiac muscle; much higher affinity for oxygen (P50 is only 1 mmHg, much lower than P50 of hgb, which is 26); only one heme group, thus dissociation curve is hyperbolic
precursor of NAD coezyme
niacin (before that tryptophan)
what happens if a pt with chronic thiamine deficiency is given a gluocse infusion without thamine supplementation?
acute cerebral damage
UV dmg mechanism, and repair method
Pyrimidine dimers in DNA; recognized by specific endonucleases that nick strand at thymine dimer, which signals removal by the 5’ to 3’ exonuclease activity of DNA polymerase; deficiency in UV-specific endonuclease results in xeroderma pigmentosum
