qbank - biochem Flashcards
citrullination
tissue inflammation -> arginine residues (e.g. in vimentin) are enzymatically converted -> cirulline -> different shape -> immune response b/c they become Ags. this process is exaggerated in RA, so anti-CCP (cyclic citrullinated peptide) Abs = 95-98% specific for RA
anti-centromere Abs
found in majority of CREST syndrome
anti-dsDNA
specific to SLE
rheumatoid factors
auto-Abs that target Fc portion of human IgG. occur in ~80% of RA patients, ~10% of healthy patients, ~30% of SLE, ~100% of mixed cryoglobulinemia and other inflammatory conditions
ANA
antinuclear Abs = Abs to nuclear basic proteins = nonspecific finding in many connective tissue d/os. ANAs occur in IgM form in pts w/RA but less frequently than RF.
anti-phospholipid Abs
found in pts w/SLE and antiphospholipid Ab syndrome, which -> hypercoagulability, paradoxical PTT prolongation, and recurrent miscarriages
homocystinuria
most common inborn error of methionine metabolism. present at age 3-10 w/lens subluxation, intellectual disability (~50%), marfanoid habitus, osteoporosis, and possibly thromboembolic events. typically caused by cystathionine synthetase defficiency, which requires pyridoxine (B6) as a cofactor. B6 -> enzyme activity and dec. homocysteine levels
vit C
necessary cofactor for hydroxylation of proline and lysine in collagen.
excess methionine in homocystinuria pts
-> inc. plasma homocyseine b/c it can’t be metabolized to cysteine. therefore, Tx of homocystinuria involved methionine restriction
thiamine
B1. deficiency -> dry and wet beriberi and wenicke-korsakoff syndrome
tyrosine
nonessential AA. precursor for DA, epi, and NE
vit K fxn
post-translational conversion of glutamate -> gamma-carboxyglutamic acid = necessary for fxn of many clotting factors and reg. proteins in coag. cascade
aging effects on skin
gradual thinning of epidermis, reduced subQ fat, blood vessels, hair follicles, sweat ducts, and sebaceous glands. dec. subQ fat -> skin becomes atrophic, more vulnerable to damage. dec. dermal collagen and elastin -> dec. reticular support -> sagging, wrinkles
fibrillin-1
protein found in lots of connective tissues. aids in dev. of extracellular matrix microfibrils -> scaffolding for elastic fiber deposition. inherited defect -> marfans
KATP channels
K channels in pancreatic beta cells that close when ATP/ADP ratio is high -> depolarization -> V-gated Ca channels open -> insulin release. ATP is generated when a lot of glucose enters via GLUT-2 transporters. defects in KATP -> T2DM. sulfonylereas close KATP channels
methemoglobin
Hb w/Fe3+. can’t bind O2. O2 affinity of remaining Fe2+ Hb is increased -> left shift of dissociation curve. can be caused by nitrates. -> dusky skin discoloration, dec. O2 content, carrying capacity, and % saturation, normal PO2.
receptors w/intrinsic enzyme activity
receptor tyrosine kinase. 3 structures: extracellular domain (binds growth factor), transmembrane domain, and cytosolic domain (enzyme) . MAP-kinase signaling: receptor autophosphorylates and triggers phosphorylation of Ras protein. e.g. growth factor receptors: EGF, PDGF, FGF
receptors w/o intrinsic enzyme activity
tyrosine-kinase associated receptor. 3 structures: extracellular domain, transmembrane domain, and cytosolic domain (lacks enzymatic activity). JAK/STAT signaling: receptor activates Janus kinases (JAKs), which phosphorylate STATS (signal transducers and activators of transcription. e.g. receptors for cytokines, growth hormone, prolactin, IL-2
folate fxn
crucial for DNA synthesis and conversion of vit B12 -> one of its coenzyme forms. necessary for dTMP production, which is needed to supply the four nucleotide precursors of DNA replication. folate deficiency -> megaloblastosis and erythroid precursor cell apoptosis.
thymidine kinase salvage pathway
normally makes 5-10% of dTMP
glutamine
major source of N in synthesis of nucleotides, so contributes N atom to biosynthesis of dUMP.
beta-thalassemia
microcytic anemia, increased Hb F (alpha2gamma2), and Hb A2 (alpha2delta2). hypochromia and poikilocytes, including target cells. Fe supplements don’t help. mutations -> dec. transcription, processing, and translation of beta-globin mRNA: heme synthesis = normal.
elastin structure
plasticity and recoil ability are attributable to unique desmosine crosslinking between 4 different lysine residues on 4 different elastin chains. crosslinking is accomplished by action of extracellular lysyl hydroxylase. mostly made of non-polar AAs glycine, alanine, and valine, which some proline and lysine
alpha1-antitrypsin deficiency
alpha1-antitrypsin inhibits the action of endogenous proteolytic enzymes that hydrolyze proteins like elastin, particularly neutrophil-secreted elastase. so deficiency -> excessive degradation of elastin in lungs and liver -> panacinar emphysema and cirrhosis
elasin differs from collagen in 3 main ways
- very few proline and lysine residuese are hydroxylated in elasin
- triple helix formation = basis of collagen, NOT elastin
- triple helix formation in collagen is initiated by hydroxylation, glycosylation and interchain disulfide bridges at C-terminus of procollagen molecule. these modifications do not occur in elastin formation
scurvy
caused by impaired collagen formation: hemorrhages, subperiosteal hematomas, hemearthrosis, gingival swelling, secondary periodontal infection, anemia, hyperkeratotic papular rashes, impaired wound healing, weakened immune response
ascorbic acid fxn
accelerates hydroxylation and amidation reactions: activation of prolyl and lysyl hydroxylase precursors, both necessary for hydroxylation of procollagen. collagen contains lots of hydroxyproline, so quantity and quality = reduced by vit. C deficiency
B1
thiamine
B2
riboflavin. deficiency: cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization, ariboflavinosis
B6
pyridoxine. deficiency: cheilosis, glossitis, dermatitis, peripheral neuropathy
zinc deficiency
acrodermatitis enteropathica, growth retardation, infertility
pellagra
3 Ds: dermatitis (rough, scaly, sun-exposed), diarrhea (columnar epithelium atrophy), dementia (neuronal degeneration in brain and cord). 2/2 niacin (B3) deficiency
niacin
B3. essential component of coenzymes NAD and NADP. pivotal role in intermediary metabolism of cells, accepting electrons and donating H+s. metabolism of FAs, AAs, and carbs, critical in HMP shunt. obtained from diet or made from tryptophan. happens w/corn-based diet, alcoholics, and chronic dz (e.g. HIV).
carotene
vit A precursor
tyrosine precursor
phenylalanine. necessary for catecholamine synthesis.
arginine = precursor of
NO, urea, ornithine, agmatine. necessary for creatine formation
orotic acid
precursor of pyrimidine. overproduced from carbamoyl phosphate by CPS II when there is a block in the urea cycle. found in OTC deficiency, citrullinemia, and argininosuccinic aciduria
individual subunits of Hb
structurally analogous to myoglobin: hyperbolic oxygen-dissociation curve.
left-shifted O2 dissociation curve
high O2 affinity Hb (e.g. fetal) or inc. pH, dec. T, or dec. 2,3-diphosphoglycerate
right-shifted O2 dissociation curve
low O2 affinity Hb, e.g. dec. pH, inc. T, inc. 2,3-diphosphoglycerate
ubiquitin
protein that undergoes ATP-dependent attachment to other proteins, labeling them for degradation. tagged proteins ender proteasome and are degraded -> peptides. important for muscle wasting, cell cycle regulation, DNA repair, disposal of misfolded proteins/enzymes. impairment of this system can contribute to neurodegenerative d/os, e.g. AD and PD
acetylation
histone acetylation promotes formation of euchromatin
gamma-carboxylation
vit K dependent -> clotting factors II, VII, IX, X, proteins C and S. inhibited by warfarin
glucuronidation
step 2 of hepatic processing of bilirubin: conjugation of bilirubin w/glucuronic acid in ER. disrupted in Crigler-Najjar
3 steps of hepatic bilirubin
- carrier-mediated passive uptake of bilirubin and sinusoidal membrane 2. conjugation of bilirubin w/glucuronic acid in ER 3. active biliary excretion of water-soluble, nontoxic bilirubin-glucuronides
phosphorylation
adding a phosphate group: commonly involved in regulation of enzyme activity
arginase deficiency
arginine -> ornithine and urea. spasticity is commonly mistaken for cerebral palsy. Tx w/low protein, arginine-free diet and administration of synthetic essential AA protein
glutamine
major AA in blood b/c it transports ammonia from peripheral tissues to kidney. in nephron, amide nitrogen is hydrolyzed by glutaminase to regenerate glutamate and free ammonium, which is excreted in urine
homocysteinemia
occurs w/vit B6, B12, and folate deficiencies. -> atherosclerosis and thrombotic events
gamma-aminobutyrate
GABA. inhibits presynaptic transmission in CNS and retina. formed by decarboxylation of glutamate catalyzed by GAD
PRPP synthetase abnormality
-> gout. often X-linked. PRPP synthetase produces activated ribose necessary for de novo purine/pyrimidine synthesis. mutation -> inc. purine -> inc. degradation -> hyperuricemia
gout
Sx: 1st metatasophalangeal joint or knee. swelling, erythema, exquisite tenderness. rapid onset. Dx: needle-shaped, negatively birefringent crystals. Tx: NSAIDS. colchicine = 2nd line. can use allopurinol for prevention after acute resolution
target of gout Tx
neutrophils, which phagocytose crystals and release cytokines and inflammatory mediators -> amplified inflammatory response
colchicine MoA
impairs neutrophil migration and phagocytosis by interfering w/microtubule formation and decreases neutrophil activation
eosinophils
defend against parasites. pathogenic in asthma, allergy, hypereosinophilic syndromes, and vasculitides (e.g. chrug-strauss)
lymphocytes
delayed-type hypersensitivity
cromolyn sodium
inhibits mast cell degranulation. used to treat asthma and allergies
primary structure
sequence of AAs linked by covalent peptide-bonds
secondary structure
alpha-delix or beta-sheet due to H-bonding
tertiary structure
overall shape protein assumes following compact folding of secondary structure. involves many forces: ionic bonds, hydrophobic interactions, H-bonds, and disulfide bonds
disulfide bonds
very strong covalent bonds between 2 cysteine residues w/in same polypeptide chain. enhance protein’s ability to withstand denaturation
RNA polymerase I
produces 18S, 5.8S, and 28S ribosomal RNA. fxn: form essential ribosomal components. only operates in nucleolus
RNA polymerase II
produces mRNA: translated by ribosome to form specific proteins; small nuclear RNA: involved in mRNA splicing & transcription regulation; and microRNA: causes gene silencing via translation arrest or mRNA degradation. most regulated type of RNA polymerase
RNA polymerase III
produces tRNA: adaptor molecule linking codons w/specific AAs; 5S rRNA: essential component of 60S ribosomal subunit
nucleolus
site of ribosomal subunit maturation and assembly. RNA polymerase I synthesizes most rRNA from w/in it
endonuclease
break phosphodiester bond w/in nucleotide chain in DNA and RNA. important in DNA repair and RNA splicing. present throughout nucleoplasm
pigment gallstones
10-25% of gallstones in US. more common in rural Asians, women, and elderly. arise 2/2 infection of biliary tract -> release of beta-glucuronidase by injured hepatocytes and bacteria -? hydrolysis of bilirubin glucuronides and inc. unconjugated bilirubin in bile. common biliary pathogens = E coli, ascaris lumbricoides, and liver fluke opishtorchis sinensis
desmolase
catalyzes formation or destruction of C-C bonds w/in a molecule. plays a role in respiration and fermentation
7alpha-hydroxylase
converts cholesterol -> bile acids, reducing likelihood of cholesterol gallstones
aromatase
catalyzes conversion of androgens -> estrogens
western blot
used to identify specific proteins. 1st, proteins are separated by gel electrophoresis, then transferred to nitrocellulose membrane + probed w/specific Ab. Then washed + treated w/Ab marker.
northern blot
used to identify specific RNA sequences. separated by gel electrophoresis, transferred to membrane, hybridized w/probe containing complementary mRNA sequence
southern blot
used to identify specific DNA sequences. DNA is extracted, fragmented using restriction endonucleases, separated by gel electrophoresis, transferred to membrane, cross-linked to membrane w/UV exposure, hybridized w/complementary probe. mutations at restriction sites alter DNA fragment lengths, altering electrophoresis migration patterns
southwestern blot
used to identify DNA-binding proteins. similar to southern and western technique. DNA-binding proteins are recognized by their ability to bind specific oligonucleotide probes
microarray
similar to southern and northern blot, but involves hybridization of large number of probes at once.
gluconeogenesis
becomes principal energy source after 12-18 hrs of fasting. uses many bidirectional enzymes involved in glycolysis. initial committed step = conversion of pyruvate -> oxaloacetate, then oxaloacetate to phophoenolpyruvate.
glycogenolysis
lasts only until glycogen stores are depleted: 12-18 hrs. first step = breakage of 1-4 glycosidic linkage -> G1P.
palmitic acid
1st fatty acid produced from acetyl CoA during lipogenesis in fed state. during prolonged fasting, lipolysis -> generation of glycerol and FAs.
lac operon
= lactose operon. regulated by 2 distinct mechanism: negatively by binding of the repressor protein to the operator locus and positively by cAMP-CAP binding upstream from the promoter region. constitutive expression of the structural genes of the lac operon occurs w/mutations that impair the binding of the repressor protein (Lac I) to its regulatory sequence in the operator region
nitrogen carriers
alanine and glutamine
glutamine
produced by most body tissues, catabolized by gut and kidney for maintenance of cellular metabolism and acid-base regulation. can be converted -> alanine -> bloodstream
glucose-alanine cycle
helps remove excess nitrogen. glucose is converted -> alanine by muscle to pick up nitrogen from catabolized AAs. the liver then converts this alanine into glucose and urea
alpha-ketoglutarate
accepts the amino group in almost all aminotransferase rxns, including alanine aminotransferase. amino groups are funneled from alanine to glutamate during protein catabolism.
heme oxygenase
converts heme -> biliverdin, a pigment that makes buises greenish after several days
ferrochelatase
final enzyme in heme synthesis. inhibited by lead.
uroporphyrinogen decarboxylase
enzyme in heme synthetic pathway that is defective in the most common type of porphyria, PCT
bilirubin glucuronyl transferase
enzyme necessary for conjugation of bilirubin to glucuronic acid. problems with this enzyme (genetic or drugs) impairs liver’s ability to conjugate bilirubin
methemoglobin reductase
catalyzes reduction of methemoglobin to hemoglobin via NADH oxidation. unclear physiological significance. activated by methylene blue
methionine formation
methyl-tetrahydrofolate donates a methyl group to homocystine to form methionine and tetrahydrofolate. cobalamin (B12) is a necessary cofactor. tetrahydrofolate rapidly accepts 1C moieties and re-enters cycle. so in B12 deficiency, tetrahydrofolate can’t be regenerated, impairing folate metabolism
why does B12 deficiency affect neurons, while folate deficiency doesn’t?
only B12 is responsible for conversion of methylmalonyl CoA -> succinyl coA. this results in incorporation of nonphysiologic FAs into neuronal lipids. both show elevated homocysteine, only B12 has elevated methylmalonyl CoA.
leptin
protein hormone produced by adipocytes in proportion to quantity of fat stored. acts on arcuate nucleus of hypothalamus to inhibit production of neuropeptide Y (decreasing appetite) and stimulates production of alpha-MSH (increasing satiety). mutations -> hyperphagia + profound obesity
transamination rxns
occur between AA and alpha-keto acids. amino group is transferred to alpha-deto acid, which becomes an AA. pyridoxical phosphate B6) serves as a cofactor in AA transamination and decarboxylation rxns
thiamine
B1. coenzyme for transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase
riboflavin
B2. used in dehydrogenase rxns involving FMN and FAD
niacin
B3 = nicotinic acid. enables dehydrogenases to form NAD and NADP. deficiency -> pellagra: 4 Ds: dermatitis, diarrhea, dementia, death
biotin
B7. water-soluble cofactor for all 4 carboxylase enzymes. involved in synthesis of FAs, isoleucine, valine, and gluconeogenesis.
HbF
= alpha2gamma2. dominates in newborns. high affinity for O2, produced during the final 7 months of gestation. switch to HbA (alpha2beta2) occurs during first 6 months of life
HbA2
= alpha2delta2. normal variant that comprises 2-5% of normal adult Hb
Hb Gower
zeta2epsilon2 = earliest Hb found in fetus. synthesized by yolk sac, replaced by Hb Portland, then Hb Gower 2 before HbF production begins at 10-12 wks
Hb Bart
= gamma4. found in homozygous alpha-thal, where 0 alpha chains are synthesized. very high O2 affinity, does not release it to tissues -> hypoxia -> hydrops fetalis -> death in utero
HbS aggregates
in deoxygenated state. HbS polymers form fibrous strands that reduce RNC membrane flexibility and promote sickling. sickling occurs under all conditions associated w/anoxia: low pH, high 2,3-DPG. also low blood volume
SS mutation
nonpolar valine replaces charged glutamate at position 6 of beta-chain
2,3-DPG
ionically binds 2 beta chains and stabillizes the taut (T) deoxygemoglobin. this binding decreases O2 affinity of Hb and facilitates O2 release to tissues. when 2,3-DPG is depleted, O2 affinity increases -> O2 uptake
Kozak sequence
defined by the sequence: (gcc)gccRccAUGG, where R = adenine or guanine. when AUG is positioned near beginning of mRNA w/in Kozak, it serves as an initiator (-> ribosome binding). if A or G at R is replaced by C or G, initiation won’t work right (e.g. in thalassemia intermedia).
translocation
catalyzed by elongation factor eEF2, requires FTP hydrolysis
peptide bond formation
catalyzed by peptidyl transferase on eukaryotic ribosomes. defect in mRNA coding for ribosomes would interfere w/this fxn
termination of polypeptide sequence
occurs at stop codons. happens early when mutations create misplaced stop codons
protein targeting
achieved by AA sequence of N-terminal section of formed protein. often removed from final protein once it reaches it’s destination
thalassemia intermedia
form of beta-thal that is clinically less severe than beta-thal major. hypochromic, microcytic anemia = classic lab finding of thalassemia.
thalassemia RBC morphology
variable depending on type, but can include anisopoikilocytosis, target cells, tear drop cells, and/or heintz bodies
spherocytosis
caused by variety of molecular defects in genes encoding RBC membrane proteins, e.g. spectrin, ankyrin, band 3 protein, protein 4.1
mitochondrial biochemical processes
b-oxidation of FAs, ketogenesis, TCA cycle, parts of urea cycle (carbamoyl phosphate synthetase 1 and ornithine transcarbamoylase) and pyruvate carboxylation
transketolase
enzyme of pentose phosphate pathway. uses B1 as a cofactor. all pentose phosphate pathway rxns occur in cytoplasm
pyruvate carboxylase
catalyzes initial step in gluconeogenesis by converting pyruvate to oxaloacetate. requires biotin as a cofactor. fxns w/in mitochondria
