Biochem Flashcards
What is the structure of chromatin? Heterochromatin? Euchromatin?
Beads on a string. Histone octamer=2 x (H2A, H2B, H3, H4). DNA string. H1 bound to nucleosome (histone) and DNA.
HC=Highly condensed. Inactive
Euchromatin=active, truly transcribed.
What is the purpose of DNA methylation? At CpG islands? Histone methylation? Acetylation?
DNA methylation helps it be recognized by mismatch repair enyzmes
At CpG islands=mute
Histone methyl=mute
Acetyl=active
Which nucleotides are purines? How are purines made? What substances are required?
PURe As Gold (adenosine, glycine)
Ribose 5-P is turned into PRPP by PRPP synthetase.
A base is then added to form IMP.
IMP can be converted to AMP or GMP.
Which NTs are pyrimidines? Structure? How are they made? Requirements?
CUT the PY=cytosine, uracil, thymidine
Pie is sweet-requires carbamoyl phosphate and aspartate.
A pie is a circle-only one ring
Glutamine and CO2 are converted to carbamoyl phosphate by CPS-II.
Aspartate is added to make orotic acid.
PRPP is added to orotic acid to form UMP.
UMP is converted to UDP
UDP can be converted to CTP.
UDP can also be converted to dUDP by ribonucleotide reductase
dUDP is converted to dUMP which is converted to dTMP by thymidylate synthase which requires THF.
DHF is converted to THF by DHFR.
Describe the purine salvage pathway.
AMP is converted to adenine by APRT.
It can also be converted to adenosine.
Adenosine is converted to Inosine by ADA.
Inosine is conv. to hypoxanthine.
Hypoxanthine can be converted to IMP by HGPRT
It can also be converted to xanthine by XO
GMP is converted to guanosine then guanine.
Guanine can be converted to GMP by HGPRT
It can also be converted to xanthine.
Xanthine is converted to uric acid by xanthine oxidase
Uric acid is excreted in the urine.
What is adenosine deaminase deficiency? Pathophys? Consequences?
Excess ATP leasd to NT imbalances, descrease lymphocyte count. Major cause of SCID.
Symptoms of Lesch-Nyhan? Pathophys?
Absent HGPRT
Hyperuricemia, gout, pissed off (aggression/self-mutilation), retardation, dystonia)
What are the differences between DNAP III and DNAP I. Direction of DNA, RNA, and protein synth? mRNA read?
III has 5’ to 3’ synth and 3’ to 5’ exonuclease (proofreading)
I has 5’ to 3’ exonuclease for RNA primer.
5’ to 3’ and N to C
Describe the lac operon and how and when it leads to lactose metabolism
Low glucose leads to adenylyl cyclase leads to cAMP leads to CAP which leads to transcription of lactose metabolism proteins.
High lactose leads to an unbinding of a repressor protein from the operator site which leads to increase transcription.
In what phase does NT excision repair occur? What does a defect lead to? Same questions for mismatch repair? What does a defect of nonhomologous end joining lead to?
NT excision=G1=xeroderma pigmentosum
mismatch=G2=HNPCC
non homologous=ataxia telangiectasia, fanconi anemia, BRCA?
What does M6P signal? Where does it occur? Where does n-linked oligosaccharide addition occur? What does COP I do? COPII? Clathrin?
Trafficking to lysosome. Golgi
oligosaccharide addition-RER
COPI-Retrograde along golgi, golgi to ER
COPII-ER to golgi
Clathrin-trans golgi to lysosomes or plasma membrane, PM to endosomes
What is the role of the peroxisome?
catabolism of VLCFA, branched chain FAs, and AAs.
What are the function of microfilaments? What is an example? Same questions for intermediate filaments (examples)? Same questions for microtubules. What immunohistochemical stain is used for the various intermediate filaments/tissue location?
Micro-muscle contr., cytokinesis=actin
intermediate-maintain cell structure=vimentin (CT), Desmin (muscle), cytokeratin (epithelial), GFAP (neuroglial), neurofilaments (Neurons)
microtubules-movement, cell division=cilia, flagella, mitotic spindle, axonal trafficking, centrioles
What is the structure of cilia? What is kartagener syndrome? Another name? symptoms?
9+2 arrangement of microtubule doublets
Primary ciliary dyskinesia. No axonemal dynein which links doublets.
Male and female infertility (sperm and fallopian tube), increased risk of ectopic, bronchiectasis, recurrent sinusitis, and situs inversus.
Which types of collagen make up the different tissues?
Be (So Totally) Cool, Read Books
type I=bone, Skin, tendon
II=cartwolage
III=reticulin (blood vessels)
IV=basement membrane
Describe the various steps of collagen synth, where they occur, and what can go wrong with each step.
synth (RER)=Translation of alpha chains, usually gly, pro, lys
Hydroxylation of pro/lys=Vit. c needed (scurvy).
Glycosylation=allows the formation of the triple helix of 3 alpha chains (OI)
Exocytosis from RER and cell into EC space
Proteolytic processing=cleavage of disulfide bonds forming tropocollagen
Cross-linking=covalent lysine-hydroxylysine crosslinkage by copper containing lysyl oxidase to make collagen fibrils. (Ehlers-Danlos and Menkes)
What is the genetics of OI? Pathophys? Symptoms?
AD
Decreased production of normal type I collagen (can’t form triple helix)
multiple fractures, blue sclerae, hearing loss, dental imperfections.
symptoms of ehlers-danlos? Types/collagen involved? pathophys?
hyperextensible skin, tnedency to bleed, hypermobile joints.
Berry and aortic aneurysms, organ rupture
hypermobility type (most common)
Classical type=both skin and joint (type V collagen)
VAscular type (vascular and organ rupture)=type III collagen
What are the genetics of Menkes disease? Pathophys? Symptoms?
X linked
Impaired copper absorption and transport due to defective menkes protein (ATP7A)—>less lysyl oxidase.
Brittle kinky hair, growth retardation, and hypotonia
What do southern/northern/western/southwestern blot quantify?
SNoW DRoP
Southern=DNA
Northern=RNA
Western=Protein
Southwestern=DNA-binding proteins
What is the difference between a direct ELISA and an indirect ELISA?
Direct ELISA-test antibody connected to a color generating enzyme to see if a specific antigen is present
Indirect ELISA-test antigen or antibody used to see if a specific antibody or antigen is present. Another antibody coupled to a color generating enzyme then checks to see if the test antigen or antibody bound.
What can karyotyping be performed on? How does FISH work?
Bone marrow, amniotic fluid, placental tissue
flourescent DNA/RNA probe binds to a gene site on a chromosome. Localization of genes/anomalies.
What is codominance?* Variable expressivity? Incomplete penetrance? Pleiotropy? Anticipation?* Loss of heterozygosity?* Dominant negative mutuation? Linkage disequilibrium? Mosaicism?* Locus heterogeneity?* Allelic heterogeneity?* Heteroplasmy? Uniparental disomy?* Imprinting?* Examples of each?*
codominance? both allelles contribute to phenotype=ABO, alpha 1 antitrypsin
Variable expressivity? phenotype varies with same genotype
Incomplete penetrance? Not all individuals with genotype show phenotype
Pleiotropy? One gene leads to multiple phenotypic effects.
Anticipation? Increased severity over generations; trinucleotide repeats
Loss of heterozygosity? patient develops a mutaiton in a tumor suppressor gene, the complementary allele must be deleted before cancer develops. Not true of oncogenes.
Dominant negative mutuation? Exerts a dominant effect. A heterozygote produces a non-functional altered protein that also prevents normal protein from functioning.
Linkage disequilibrium? Certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in populations, not families.
Mosaicism? Genetically distinct cell lines in same individual. Somatic=after fertilization, propagates through multiple tissues. Gonadal=only in egg or sperm cells (future generations)=McCune Albright
Locus heterogeneity? Similar phenotype due to mutations at different loci. Albinism.
Allelic heterogeneity? Different mutations in the same locus produce the same phenotype. Beta thalassemia
Heteroplasmy? Normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease.
Uniparental disomy? Offspring received 2 copies of a chromosome from one parent and no copies from the other
Imprinting? At some loci, only one allele is active. The other is inactive. With one allele inactivated, if the active allele is deleted—>disease. Prader Willi and Angelman=chromosome 15.
What is hardy weinberg genetics? When do they apply? How are they adapted in x-linked recessive diseases?
p^2 + 2pq + q^2=1 and p+q=1.
2pq = heterozygosity
p^2 and q^2 =homozygous
The frequency of x-linked recessive disease in males is q and in females is q^2.
No mutations occurring, no net migration, completely random mating.
What is the pathophys of prader-willi? Symptoms? Same questions for angelman?
Prader-Willi=Paternal gene deleted, hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.
AngelMan Syndrome=Maternal gene deleted. Happy puppet=inappropriate laughter, seizures, ataxia, and severe intellectual disability.
What are mitochondrial myopathies like? Cause?
Heteroplasmy. Rare. Myopathy, lactic acidosis, and CNS disease. Secondary to failure in oxidative phosphorylation. Muscle biopsy shows ragged red fibers.
What are some x linked recessive disorders?
Be Wise, Fool’s GOLD Heeds Silly HOpe
Bruton’s agammaglobulinemia, Wiskotts aldrich, fabry disease, G6PD, ocular albinism, lesch-nyhan, duchenne and becker muscular dystrophy, hunter syndrome, Hemophilia A and B, and Ornithine transcarbamylase deficiency
What are the genetics of duchenne muscular dystrophy? pathophys? Symptoms? Age? complications? Diagnosis? How does becker differ from Duchenne?
X linked-frameshift
Truncated dystrophin, loss of anchoring–>myonecrosis
Weakness beginning in pelvic girdle muscles, progresses up. Pseudohypertrophy of claves (fibrofatty replacement),
Gower maneuver, waddling gait.
Onset before age 5
Dilated cardiomyopathy
Increased CPK and aldolase; Western blot and muscle biopsy
BECKER
X-linked-non frameshift insertions into dystrophin gene.
Less severe, onset in adolescence
Genetics of myotonic type I muscular dystrophy? Pathophys? Symptoms?
AD. CTG trinucleotide repeat expansion in the DMPK gene—>abnormal expression of myotonin protein kinase—>My Tonia, My Testicles (atrophy), My Toupee (frontal balding), and My Ticker (arrhythmia) , cataracts.
What is the inheritance of fragile x? Which gene is involved? What is the mutation like? What are the findings?
Extra large testes, jaw (with long face), ears
Autism, Mitral valve prolapse
Graham!
X linked-CGG repeat-FMR1 gene.
What are 4 trinucleotide repeat expansion diseases? What patterns of NTs are in each? What are the genetics like?
Try Hunting for my fried eggs (Trinucleotide: Huntingtons, myotonic type musc dyst, friedrichs ataxia, fragile X)
Fragile X, Huntingtons, and myotonic dystrophy are each C-blank-G
Friedrichs is GAA.
X-Girlfriends First Aid Helped Ace My Test (Fragile X=CGG, Friedrich=GAA, Huntingtons=CAG, Myotonic=CTG
May show anticipation
What are some symptoms/associations of down syndrome? Chromosome involved? Same questions for Edwards? Same questions for Patau? How are the 3 differentiated during pregnancy screening?
DS=chromosome 21 (Drinking age starts with D)
intellectual disability, gap b/w first 2 toes, duodenal atresia, hirschsprungs, ASD, Brushfield spots, alzheimers, ALL and AML.
First tri U/S=incr. nuchal translucency, hypoplastic nasal bone, decr. serum PAPP-A, free beta hCG is incr.
2nd tri quad screen=decr. alpha fetoprotein, incr. beta hcg, decr. estriol, and incr. inhibin A
Edwards=chromsome 18 (election age starts with E)
Intell. disabil., rocker bottom feet, small jaw, low set ears, clenched hands with overlapping fingers, prominent occiput, congenital heart disease, death within a year
1st tri=PAPP=A and beta hcg are decreased
Quad=decr. alpha fetoprotein, decr beta hcg, decr. estriol and decr. or normal inhibin
Patau=chromosome 13 (puberty starts with P)
intell. disabil, rock bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease, cutis aplasia. Death in first year
1st tri=decr. free beta hcg, decr PAPP-A, and incr. nuchal translucency.
What are the findings of Cri-Du-Chat? What part of the genetic code is involved?
Congenital microdeletion of short arm of chromosome 5.
Microcephaly, moderate to severe intellectual disability, high pitched mewing/crying, epicanthal folds, cardiac abnormal (VSD)
What are the findings in Williams Syndrome? What part of the genetic code is involved? Which gene is affected?
Congenital microdeletion of long arm of chrom. 7 (part of elastin gene)
Elfin facies, intellectual disabil, hypercalcemia (incr.sens. to vit. D), well developed verbal skills, extreme friendliness with strangers, and CV problems.
What are the symptoms of 22q11 deletion syndromes both individually and collectively? What part of the body is involved?
CATCH 22=cleft palate, abnormal facies, thymic aplasia, cardiac defects, and hypocalcemia secondary to parathyroid aplasia
3rd and 4th pharyngeal pouches
DiGeorge=hypocalcemia, thymic aplasia, and cardiac defects
Velocardiofacial syndrome=palate, facies, and cardio
What is the function of Vit. A? Another name? What occurs in defiency? What is it used to treat? What is the main worry with excess?
Retinol
Antioxidant
Part of visual pigments
Differentiation of epithelial cells into specialized tissue (prevents squamous metaplasia)
Used to treat measles, AML subtype M3, wrinkles, and acne
Nightblindness (nyctalopia) dry, scaly skin (xerotis cutis) corneal degeneration (keratomalacia) Bitot spots on conjuctiva Immunosuppression
In excess—>teratogenic (cleft palate, cardiac)
Before isotretinoin is prescribed for severe acne, a pregnancy test is given.
