Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
257 Cards in this Set
- Front
- Back
|
heterochromatin
|
transcriptionally inactive
condensed = sterically inaccessible |
|
|
euchromatin
|
transcriptionally active
less condensed = accessible to DNA transcription proteins |
|
|
nucleosome consists of
|
H2A, H2B, H3, H4
H1 is not in the nucleosome - exists between nucleosomes |
|
|
amino acids in histone proteins
|
lots of lysine and arginine (positive charge)
|
|
|
G-C bond vs A-T bond
|
3 hydrogen bonds in G-C bond - higher melting point
2 hydrogen bonds in A-T bond |
|
|
nucleoside vs nucleotide
|
nucleoside is base + ribose
nucleotide is base + ribose + phosphate |
|
|
amino acids needed for purine synthesis
|
glycine, aspartate, glutamine
|
|
|
purine precursor
|
PRPP -> IMP -> AMP or GMP
|
|
|
pyrimidine precursor
|
orotic acid + PRPP -> UMP ->->-> CTP, TMP
|
|
|
purine and pyramidine synthesis requires
|
glycine, aspartate, glutamate, THF
|
|
|
hydroxyurea
|
inhibits ribonucleotide reductase needed for conversion of ribonucleotides into DEOXYribonucleotides
|
|
|
6-mercaptopurine
|
blocks purine synthesis
|
|
|
5-fluorouracil
|
inhibits thymadine synthase
decreased dTMP |
|
|
methotrexate
|
inhibits dihydrofolate reductase
decreases dTMP |
|
|
trimethoprim
|
inhibits bacterial dihydrofolate reductase
antibiotic |
|
|
orotic aciduria
|
inability to convert orotic acid to UMP for pyrimadine synthesis
auto recessive increased orotic acid in urine megaloblastic anemia that does not respond to B12 or folic acid no hyperammonemia treat with oral uridine |
|
|
adenosine deaminase deficiency
|
excess ATP and dATP causes inhibition of ribonucleotide reductase -> prevents DNA synthesis
major cause of SCID by decreasing lymphocytes |
|
|
lesch nyhan syndrome
|
deficiency of HGPRT
X linked recessive --> excess purine synthesis -> hyperuricemia -> gout build up of uric acid -> retardation, self-mutilation, agression |
|
|
only amino acid with one codon
|
methionine (AUG)
|
|
|
silent mutation
|
base change usually in 3rd position of codon
same AA encoded |
|
|
missense mutation
|
changed AA
if new AA is similar to chemical structure - conservative mutation |
|
|
nonsense mutation
|
"stop the nonsense"
change resulting in early stop codon |
|
|
frameshift mutation
|
change resulting in misreading of ALL nucleotides downstream
often causes a truncated nonfunctional protein |
|
|
DNA polymerase III
|
prokaryotic only
elongates leading strand by adding deoxynucleotides to 3' end (5'->3') proofreads with 3'->5- exonuclease activity |
|
|
DNA polymerase I
|
prokaryotic only - degrads RNA primer and fills in the gap with DNA
|
|
|
fluroquinolones
|
inhibit DNA gyrase (prokaryotic specific)
|
|
|
xeroderma pigmentosum
|
defect in nucleotide excision repair - prevents repair of thymidine dimers due to UV exposure
dry skin, and increased melanoma and other cancer |
|
|
hereditary nonpolyposis colorectal cancer (NHPCC)
|
mutation in mismatch repair system
|
|
|
types of singly strand DNA repair
|
nucleotide excision
base excision repair mismatch repair |
|
|
5' end of nucleotide has
|
the triphosphate
|
|
|
mRNA is read
|
5' to 3'
|
|
|
amino acid synthesis froms from
|
N to C
|
|
|
most abundant type of RNA
|
rRNA
|
|
|
longest RNA
smallest RNA |
mRNA
tRNA |
|
|
mRNA start codon
stop codons |
start: AUG
stop: UGA, UAA, UAG |
|
|
RNA polymerases of Eukaryotes
|
RNA pol 1 - makes rRNA
RNA pol 2 - makes mRNA, opens DNA at promotor site RNA pol 3 - makes tRNA |
|
|
alpha-amanitin
|
found in death caps mushrooms
inhibits RNA pol II liver failure |
|
|
prokaryotic RNA pol
|
1 protein makes all 3 kinds of RNA
|
|
|
RNA processing
|
occurs in eukaryotes only in the nucleus
cap the 5' polyA tail splice out introns only processed RNA is transported out of nucleus its only called mRNA when it is capped and tailed |
|
|
polyadenylation signal
|
AAUAAA
|
|
|
snRNP
|
key protein in spliceosome
lupus -> make antibodies to spliceosome |
|
|
splicing
|
1. primary transcript combines with snRNP to form spliceosome
2. lariat shape intermediate 3. lariat is release to remove introl and join 2 exons |
|
|
tRNA structure
|
75-90 nucleotides in clover leafform
3' end carries amino acid covalently 3' end has CCA and modified bases |
|
|
aminoacyl tRNA synthetase
|
scrutinizes aa before and after it binds tRNA
resposible for accuracy of amino acid selection |
|
|
tetracycline
|
bind 30s preventing attachment of aminoacyl tRNA
|
|
|
tRNA wobble
|
accurate binding required only for first 2 nucleotide positions of mRNA codon
the 3rd position nucleotide can be variable due to degenerate code |
|
|
protein synthesis - initiation
|
activated by GTP hydrolysis - initiation factors help assemble 40S ribosome with tRNA
form the initiation complex |
|
|
protein synthesis - elongation
|
aminoacyl-tRNA binds to A site (except the initiator tRNA which binds to the P)
ribosomal rRNA catalyzes peptide bond formation, transfers growing polypetide to the A site ribosome advances 3 nucleotides toward the 3' end of mRNA, moves the peptidyl RNA to P site A site - incoming aminoacyle tRNA P site - accomodates growing Peptide E site - holds Empty tRNA as it exists |
|
|
protein synthesis - termination
|
stop codon is recognized by release factor - completed protein is released
|
|
|
eukaryotic ribosome structure
|
40S + 60S -> 80S
Eukaryotic is Even |
|
|
aminoglycosides MOA
|
inhibit initiation complex and cause misreading of mRNA
|
|
|
chloramphenicol MOA
|
inhibits 50S peptidyltransferase
|
|
|
macrolides and clindamycin MOA
|
bind 50s prevent translocation
|
|
|
postranslational modifications
|
trimming - removing C or C terminal peptides - think zymogens
covalent alteration - phosphrylation, glycosylation, hydroxylation proteasomal degradation - attachment of ubiquitin |
|
|
ATP and GTP uses in protein synthesis
|
ATP used for tRNA Activation - charging the tRNA
GTP used for Gripping and Going places - translocation |
|
|
tumor supressor genes in cell cycle
|
Rb and p53 inhibit G1 to S progression
|
|
|
Cyclin CDK
|
must be both activated for cell cycle progression
Cyclins are cell phase specific and activate CDKs - regulatory effect on cell cycle CDK - cyclin dependent kinase that are constitutively expressed and are inactive until binding to cyclin |
|
|
cell types depending on cell growth
|
permanent - remain in G0 and regenerate from stem cells - neurons, skeletal, cardiac, RBC
stable - enter G1 from G0 only if stimulated - hepatocytes, lymphocytes labile - never go to G0, are dividing rapidly with short G1 - bone marrow, gut epithelium, skin, hair |
|
|
rough endoplasmic reticulum
|
site of synthesis of secretory/EXPORTED proteins
N linked oligosaccharide addition see alot of RER in mucus cells (goblet cells) and plasma cells |
|
|
nissl body
|
RER in neurons synthesize enzymes and neurotransmitters
|
|
|
free ribosomes
|
synthesis of cytosolic or organelle proteins
|
|
|
smooth endoplasmic reticulum
|
steroid synthesis and detoxification of durgs and poison
see a lot of SER in liver cells and steroid hormone producing cells |
|
|
I cell disease
|
defect in addition of mannose 6-phosphate to lysosomal proteins
lysosomal storage disorder - enzymes that should be in the lysosome are secreted out of the cell instead see coarse facial features, clouded cornea, restricted joints, high plasma levels of lysosomal proteins - often fatal |
|
|
COP1 protein
|
vesicular trafficking proteins - retrograde golgi -> ER
|
|
|
COP2 protein
|
vesicular trafficking proteins - anteriograde
RER -> cis golgi |
|
|
Clathrin
|
vesicular trafficking protein
trans golgi -> lysosomes AND plasma membrane -> endosomes |
|
|
golgi apparatus
|
distribution center of proteins and lipids from ER to lysosomes, secretory vesicles, plasma membrane
modifies N-oligosaccharides on asparagine adds O-oligosaccharides to serine and threonine mannose 6 phosophate targeting to lysosomes proteoglycan assembly sulfation of surgars in preteoglycans and selected tyrosines |
|
|
microtubules
|
alpha and beta tubulin in helical array
dimer has 2 GTP bound see in cilia, flagella, mitotic spindles grows slowly and collapses quickly |
|
|
dynine
|
transportation retrograde to micotubules
+ to - transportation toward the cell center |
|
|
kinesin
|
transportation anteriograde to microtuble
- to + transportation away from cell center towards the periphery |
|
|
drugs that inhibit microtubules
|
mebendazole/thiabendazole
griseofulvin vincristine/vinblastine paclitazel colchicine |
|
|
chediak-higashi syndrome
|
microtubule polymperization defect -> decreased phagocytosis
recurrent pyogenic infections, partial albinism, peripheral neuropathy |
|
|
cilia structure
|
9+2 arrangement of mcrotubules
axonemal dyenin - ATPase links peripheral 9 doublets causes bending of celium |
|
|
kartageners syndrome
|
immotile cilia due to dynein arm defect -> infertility, bronchiectasis, sinusitus
associated with situs inversus |
|
|
actin and myosin - where do you find it
|
microvilli
muscle contraction cytijeubesus adherens junctions |
|
|
microtubules - where are they found
|
cilia, flagella, mitotic spindle, neurons, centrioles
|
|
|
intermediate filaments
|
vimentin
desmin cytokeratine glial fibrillary acid proteins neurofilaments |
|
|
plasma membrane fluidity
|
high cholesterol or long saturated fatty acid content -> increased melting temperature and decreased fluidity
|
|
|
vimentin stain
|
stains connective tissue
|
|
|
desmin stain
|
stains muscle
|
|
|
cytokeratin stain
|
epithelial cell
|
|
|
GFAP stain
|
neuroglia
|
|
|
neurofilament stain
|
neurons
|
|
|
ouabain
|
inhibits Na/K ATPase pump by binding to K site
like digoxin |
|
|
cardiac glycoside
|
digoxin and digitoxin
inhibit Na/K ATPase which leads to indirect inhibition of Na/Ca exchange causes build up of Ca in muscle cell -> incresaed contraction |
|
|
type 1 collagen is found where
|
bone, skin, tendon, dentin, fascia, cornea, late wound repair
acronym: bONE - Bone is mostly type ONE collagen |
|
|
type 2 collagen is found where
|
carTWOlage is mostly type TWO
find in cartilage, vitreous body, nucleus pulposis |
|
|
type 3 collagen is found where
|
reticulin - skin blood vessels, uterus, fetal tissue, granulation tissue
|
|
|
type 4 collagen is found where
|
basement membrane or basal lamina
type FOUR is under the FLOOR (Basement membrane) |
|
|
collagen synthesis process
|
1. RER synthesis of preprocollagen - Gly-X-Y structure (X and Y are proline, hydroxyproline, or hydroxylysine)
2. hydroxulation of proline and lysine requires Vit C 3. glycosulation of pro alpha chain lysine and formation of procollagen 4. exocytosis of procollagen into extracellular space 5. proteolytic processing - cleavage of terminal region of rpcollagen into INSOLUABLE tropocollagen 6. crosslinking of tropocollagen by covalent lysine-hydroxylysin crosslinks (by lysil oxidase) |
|
|
vitamin C in collagen synthesis
|
needed for hydroxylation of proline and lysine residue
|
|
|
lysyl oxidase
|
needed to covalently crosslink collagen fibrils
needs copper |
|
|
scurvy pathogenesis
|
lack of vit C - cannot hydrxylate lysine and proline in collagen synthesis
|
|
|
osteogenesis imperfecta pathogenesis
|
most common form auto dominant defect in type I collagen -> multiple fracture, blue sclerae, hearing loss, dental imperfection
substitution of a bulkier AA for glycine cannot form triple helix procollagen form |
|
|
ehlers danlos syndrome
|
inheretance varies
defect occurs after procollagen has been secreted outside of cell and converted to tropocollgen prevent collagen filbril formation with crosslinks hyperextensible skin tendency to bleed hyperbobile joints type III collagen most effected possible: berry eneurysms, organ rupture |
|
|
alport syndrome
|
usually X linked recessive
abnormal type IV collagen progresive hereditary nephritis and DEAFness need type IV for basememnt membrane |
|
|
marfan syndrome
|
defect in fibrillin - a protein that is important in creation of a sheet around elastin
|
|
|
elastin
|
stretch protein within lungs, large arteries, leastic ligaments, vocal cords, ligamenta flava
rich in proline and glycine |
|
|
southern blot vs northern blot vs western blot
|
southern - looking for DNA with DNA
northern - looking for RNA with DNA western - looking for protein with antibody |
|
|
pleiotropy
|
1 gene has more than 1 effect on individual phenotype
|
|
|
dominant negative mutation
|
exerts a dominant effect even tho only 1 gene is effected and the other is normal
due to nonfunctional altered protein from the defective gene preventing the normal gene from functioning |
|
|
locus heterogeneity
|
mutations at different loci can produce the same phenotype
|
|
|
heteroplasmy
|
presence of both normal and mutated mtDNA -> variation expression in mitcochondrial inhereted disease
|
|
|
uniparental disomy
|
offspring recieves 2 copies of chromosome from 1 parent and none from the other
|
|
|
prader willi syndrome
|
deletion of normally active Parental allele
Chr 15 mental retardation, hyperphagia, obesity, hypogonadism, hypotonia |
|
|
angelman syndrome
|
deletion of normally Maternal allele
Chr 15 mental retardation, siezures, ataxia, inappropriate laughter |
|
|
Hypophophatemic rickets
|
known as vitamin D resistant rickets
X linked dominant increased phosphate wasting at proximal tubule - looks like rickets |
|
|
leber's hereditary optic neuropathy
|
degeneration of retinal ganglion cells and axons - acute loss of central vision
mitochondrial inheritance |
|
|
achondroplasia
|
autosomal dominant defect in FGFR3
dwarfism, short limbs head and trunk are normal size associated with advanced paternal age |
|
|
autosomal dominant polycystic kidney disease
|
adults
always bilateral enlargement of kidneys due to large cysts, flank pain, hematuria, hypertension, renal failure APKD1 on Chr. 16 also see berry aneryrsms, mitral valve prolapse, polycystic liver |
|
|
familial adenomatous polyposis
|
auto dom defect in APC gene on Chr. 5
colon covered with adenomatous polyps after puberty turns into colon cancer |
|
|
familial hypercholesterolemia
|
auto dominant defect LDL receptor
atherosclerotic disease early in life - see xanthomas, MI before age 20 |
|
|
hereditary hemorrhagic telangiectasia (osler - weber-rendu)
|
auto dominant - disorder of blood vessels
see telangiectasia, epistaxis, skin discolor, AV malformation |
|
|
hereditary spherocytosis
|
auto dom
due to spectrin or ankyrin defect see hemolytic anemia treat with splenectomy |
|
|
huntington's disease
|
tricucleotide repeat disorder - autosomal dominant
depression, progressive dementia, choreiform movements, caudate atrophy decreased GABA and ACh Chr 4 |
|
|
marfan's yndrome
|
auto dom fibrillin gene mutation
tall with long extremities, pectus excavatum, hpyerextensive joints, long tapering finbers and toes cystic medial necrosis of aorta -> diessecting aortic aneuyrsm floppy mitral valves subluxation of lenses |
|
|
MEN syndromes
|
auto dominant
MEN1 - 3Ps - pitutiary tumor, parathyroid tumor/hyperplasia, pacreatic tumor MEN2a and 2b associated with ret MEN2a - 2Ps - pheos and parathyroid tumor, + medulliary thyroid carcinoma MEN2b - 1P - pheo, medullary thryoid carcinoma, + marfanoid habitus |
|
|
Neurofibromatosis (von Recklinghausen)
|
auto dominant
NF1 on Chr 17 long arm see cafe au lait, neural tumors, lisch nodules also: optic gliomas, scoliosis |
|
|
neurofibromatosis type 2
|
auto dominant
bilateral acoustic schannomas, juveinle cateracts NF2 gene on Chr 22 |
|
|
tuberous sclerosis
|
auto dominant
see facial lesions, ash leaf spots on skin, cortical and retinal hamartoma, siezures, mental retardation, renal cyst, renal angiomyolipoma, cadiac rhabdomyomas increased astrocytoma variable penetrance |
|
|
von hippel lindau
|
auto dominant chr 3 VHL gene
hemangioblastomas of retina/cerebellum/medulla also see bilateral renal cell carcinoma |
|
|
cystic fibrosis
|
auto recessive
CFTR gene Chr 7 encodes chloride channel - needed for secretion of chloride in lungs and GI, absorption of Cl in sweat mucus plugs lungs, pancreas, liver lung infectiou by pseudomonas infertility in males due to bilateral absence of vas deferins fat soulable vitamin deficiency sweat test |
|
|
x-linked recessive disorders
|
Be Wise, Fools GOLD Heeds Silly Hope
burton agammaglobulinemia wiskott aldrich fabry G6PD def ocular albinism lesch-nyhan duchenne (and becker) hunter's syndrome hemophilia A/B females less effected due to random X inactivation |
|
|
ducheene's muscular dystrophy
|
x-linked frame shift mutation
deleted dystrophin gene -> accelerated muscle breakdown - replacement with fatty tissue pseudohypertrophy of calf muscle gower's maneuver to get up onset before age 5 |
|
|
becker's muscular dystrophy
|
x-linked dystrophin gene mutation
less severe than duchenne onset in adolescence or early adulthood |
|
|
dystrophin
|
anchors muscle fibers in skeletal and cardiac muscle
gene is the longest known human gene - high rate of spontaneous mutation |
|
|
trinucleotide repeat disorders
|
huntingtons (CAG)
Fragile X (CGG) myotonic dystrophy (CTG) friedreich ataxia (GAA) tri Hunting for Myo Fried eXggs |
|
|
fragile X syndrome
|
x linked defect of FMR1 gene
chromosomal breakage 2nd most common cause of genetic mental retardation after down's macro-orchidism, long face, long jaw, elevated ears, autisim, mitral valve prolaps CGG repeat |
|
|
down syndrome
|
trisomy 21 - most common chromosomal disorder
most common cause of mental retardation flat facies, epicathal folds, simian crease increased risk of atrial septal defect, ALL, alzheimers (early onset) usually due to nondisjunction of homologous chromosome due to advanced maternal age |
|
|
screening for down syndrome
|
quad screen
decreased AFP increased HCG decreased estriol increased inhibin A ultrasound - increased nuchal translucency |
|
|
edwards syndrome
|
trisomy 18
mental retardation unique findings: small jaw (micognathia), clenched hands death usually within 1 year of birth |
|
|
patau's syndrome
|
trysomy 13
mental retardation unique findings: cleft lip/palate, holoporsencephaly, polydactyly death within 1 year of birth usually |
|
|
robertsonian translocation
|
13, 14, 15, 21, 22 most involved chromosomes
nonreciprocal when 2 acrocentric chromosomes fuse at centromere - 2 short arms are lost, long arms remain if balanced - no abnormal phenotype, but offspring may be affected if unbalanced - miscarriage, stillbirth, chromosomal imbalance |
|
|
cri-du-chat snydrome
|
microdeletion of short arm of chromosome 5 (46, XX or XY, 5p-)
microcephaly, mental retardation, high pitch crying, epicathal folds, cardiac abnormalities |
|
|
williams syndrome
|
microdeletion of long arm of chromosome 7
elfin facies, mental retardation, hypercalcemia well developed verbal skills, extreme friendliness with strangers includes elastin gene deletion - cardiovascular problem |
|
|
22q11 deletion syndromes (2)
|
due to aberrant dev of 3rd and 4th branchial pouches
CATCH-22 Cleft palate Abnormal facies Thymic aplasia -> T cell def Cardiac defects Hypocalcemia variable presentations: digeorge syndrome - thymic, parathyroid, and cardiac defects velocardiofacial snydrome - palate, facial, cardiac defects |
|
|
fat soluable vitamines
|
A - Vision
D - Bone calcification, Ca++ homeostasis E - antioxidant K - clotting |
|
|
Vitamin C
|
water soluable
antioxidant important in collagen synthesis |
|
|
Vitamins important for metabolic funciton
|
Thiamine B1 (needed for TPP)
Riboflavin B2 (needed for FAD, FMN) Niacin B3 (needed for NAD+) Pantothenic acid B5 (needed for CoA) Pyridoxine B6 (needed for PLP, amino acid metabolism) Biotin B7 (needed for many carboxylases - gluconeogenesis, fatty acid synth) all water soluable |
|
|
Cobalamin
|
Vit B12
important for blood, CNS water soluable |
|
|
Folate
|
Vit B9
important for blood, neural dev water soluable |
|
|
symptoms of B complex vitamin deficiency
|
dematitis, glossitis, diarrhea
|
|
|
vitamin A function
|
retinol
antioxidant, needed in visual pigments, differentiation of epithelial cells into specilized tissue treats measles |
|
|
what vitamin escess is described by these symtpoms?
athralgias, fatigues, headcahge, skin changes sore throat, alopecia teratogenic - cleft palate |
vitamin A excess
|
|
|
vitamin A deficiency
|
night blindness, dry skin
|
|
|
vitamin B1 function
|
thiamine
find in thiamine pyrophosphate TPP needed in : pyruvate dehydroenase (glycolysis) alpha-ketoglutarate dehydrogenase (TCA cycle) transketolase (HMP shunt) Branched chain AA dehydrogenase |
|
|
vitamin B1 deficiency
|
impaired glucose breakdown -> ATP depletion
brain and heart affected first because highly aerobic --> wernicke-Korsakoff snydrome and beriberi often seen deficiency in alcoholics |
|
|
wernicke korsakoff
|
thiamine deficiency
confusion, ophthalmoplegia, ataxia, personality change, memory loss dmg to medial dorsal nucleus of thalamus and mammallary bodies |
|
|
dry beriberi
|
polyneuritis, symmetrical muscle wasting (peripheral nerves affected)
|
|
|
wet beriberi
|
high output cardiac failure (dilated cardiomyopathy, edema
|
|
|
vitamin b2 function
|
riboflavin
confactor for oxidation and reduction - FAD, FMN B2 = 2 ATP |
|
|
vitamin b2 deficiency
|
cheilosis - inflam of lips, scaling, fissures at corners of mouth
corneal vascularization |
|
|
vitamin b3 function
|
niacin
NAD, NADP used in redox reaction (needs nicin, tryptophan and B6) B3 = 3 ATP |
|
|
vitamin b3 deficiency
|
glossitis, pellagra (diarrhea, dermatitis, dementia)
can be caused by deficient intake OR: hartnup disease (decreased tryptophan absorption) carcinoid syndrome (increased tryptophan metabolism) isonizid (decreased B6 needed for niacin synth) |
|
|
vitamin B3 excess
|
facial flushing
niacin often used for treatment of hyperlipidemia |
|
|
vitamin B5 function
|
panthonate
essential component of CoA needed for acyl transfer and fatty acid synthase |
|
|
vitamin B5 deficiency
|
dematitis, enteritis, alopecia, adrenal insufficiency
|
|
|
vitamin B6 function
|
pyridoxine
converted to pyridoxal phosphate needed for transamination reaction (ALT and AST), decarboxylation reaction, glycogen phosphorlyase, cystathone synthesis, heme synth needed for niacin synth |
|
|
vitamin B6 deficiency
|
convulsions, hyperirritability, peripheral neuropathy, sideroblasic anemia
can be caused by isonizid and oral contriceptives |
|
|
vitamin B12 function
|
cobalamin
needed for homocystine methyltransferase - needed for transfering methyl groups important in THF formation |
|
|
vitamin B12 deficiency
|
caused by malnutrition, lack of intrsinic factor, absence of terminal ileum
-> macrocytic, megaloblastic anemia, hypersegmented PMN, neurologic sytmpoms due to abnormal myelin prolonged deficinecy - severe neurologic dmg |
|
|
folate function
|
converted to THF for 1 carbon transfer/methylation
needed for synthesis of nucleic acids in DNA/RNA |
|
|
folate deficiency
|
macrocytic megaloblastic anemia
no neurological symptoms like B12 deficiency see with alcoholism and pregnancy, certain drugs (phenytoin, sulfonamides, MTX) need to supplement folate to pregnant women to prevent neuro tube defects |
|
|
green leafy vegetables key sources of
|
vitamin A and folate
|
|
|
S-adenosyl-methionine
|
SAM transferes methyl units
via ATP and homocysteine methyltransferase requires B12 and folate |
|
|
biotin function
|
cofactor for carboxylation reaction
pyruvate carboxylase acetyl-CoA carboxylase propionyl-CoA carboxylase |
|
|
biotin deficiency
|
dermatities, alopecia, enteritis
caused by antibiotic use or excessive raw egg eating (avidin binds biotin) |
|
|
vitamin C function
|
antioxidant
iron absorption hydroxylation of proline and lysine in collagen synthesis dopamine beta-hydroxylase - convert dopamine to NE |
|
|
vitamine C deficiency
|
scurvy - swollen gums, bruising, hemarthrosis, anemia, poor wound healing
weak immune system |
|
|
vitamin D forms
|
D2 - ergocalciferol - plants
D3 cholecalciferol - milk, sun 25-OH D3 - storage form 1,25-OH D3 active form |
|
|
vitamin D function
|
intestinal absorption of calcium and phosphate
increase bone resorption |
|
|
vitamin D deficiency
|
rickets in children - bending bones
osteomalcia in adults - soft bone hypocalcemia -> tetany breast milk is low in Vit D need to supplement especailyl in dark skinned people |
|
|
vitamin D excess
|
sarcoidosis - increased vit D activation from epithelioid macrophages
hypercalcemia, hypercalciruia, loss of appeetite, stupor |
|
|
vitamin E function
|
antioxidant - protects erythrocytes and membranes from free radicles
|
|
|
vitamin E deficiency
|
increase fragility of erythrocytes -> hemolytic anemia
muscle weakness, posterior column and spinocerebellar tract demyelination |
|
|
vitamin K function
|
gamma carboxylation of flutamic acid - important for blood clotting
factors 2, 7, 9, 10, C, S synthesized by intestinal flora |
|
|
vitamin K deficiency
|
neonatal hemorrhage - see increased PT and aPTT but normal bleed time (neonates dont have bacterial production of vit K)
can occur with broad-spec antibiotics |
|
|
zinc deficiency
|
delayed wound healing, hypogonadism, decreased adult hair, dysgeusia, anosmia
need zinc for lots of things |
|
|
alcohol dehydrogenase
|
ethanol -> acetaldehyde
zero order kenetics located in cytosol needs NAD+ inhibited by fomepizole which is useful for methanol and ethylene glycol poisoning |
|
|
acetaldehyde dehydrogenase
|
acetaldehyde -> acetate
Needs NAD+ located in mitochondria inhibited by disulfuram -> accumulation of acetaldehyde -> hangover |
|
|
ethanol hypoglycemia
|
increases NADH/NAH+ ratio
this causes diversion of pyruvate-> lactate and OAA -> malate inhibits gluconeogenesis and diverts to fatty acid synth get hypoglycemia and fatty liver |
|
|
kawshiorkor
|
protein malnutrition - not enough protein, but still has caloric intake
MEAL: malnutrition, edema, anemia, liver (fatty) small child with swollen belly |
|
|
marasmus
|
energy malnutrition
tissue and muscle wasting, less subcut fat, some edema |
|
|
which metabolic processes occur in both mitochondria and cytoplasm
|
Heme Synth
Urea Cycle Gluconeogenesis |
|
|
NADPH
|
made from HMP shunt
important in anabolic processes (steroid and fatty acid), respiratory, P450, glutathion reductase (NAD+ is more catabolic) |
|
|
hexokinase vs glucokinase
|
hexokinase - high Km and high Vmax - found in liver/pancrease only - important incase excess glucose - allows storage in response to inulin
glucokinase - low Km and low Vmax |
|
|
glycolysis steps requiring ATP
|
hexokinase/glucokinase
PFK-1 |
|
|
glycolysis steps making ATP
|
Phosphoglycerate kinase
pyruvake kinase |
|
|
FBPase-2/PFK-2
|
single protein complex but 2 ezymes
PBPase activated by glucagon - promotes gluconeogenesis PFK-2 activated by insulin - promotes glycolysis |
|
|
fructose 2,6 bisphosphate
|
converted from fructose 6-P via PFK-2 activation by insulin
F 2,6 bisP is important alosteric activator of PFK-1 from glycolysis to occur (convert F6P to F1,6BP) |
|
|
arsenic
|
inhibits lipoic acid needed in pyruvate deydrogenase complex
|
|
|
cofactors needed in pyruvate dehydrogenase complex (converts pyruvate to acetyl-CoA)
|
pyrophosphate (Vit B1 - thamine)
FAD (B2 riboflavin) NAD (B3 niacin) CoA (B5 pantothenate) Lipoic acid |
|
|
purely ketogenic amino acids
|
lycine and lucine
|
|
|
pyruvate dehydrogenase deficeincy
|
back up of substrate - pyruvate and alanine
neuological problems either due to congenital or B1 deficency treat with high intake of ketogenic nutrients (ketones used by the brain) |
|
|
fates of pyruvate
|
alanine
oxaloacetate Acetyl CoA lactate |
|
|
1 acetyl CoA makes
|
3 NADH, 1 FADH2, 2CO2, 1 GTP
|
|
|
electron transport inhibitors
|
prevent proton gradient and block ATP synth
e.g. Rotenone, CN-, antimycine A, carbon monoxide |
|
|
ATPase inhibitors
|
oligomycin
see increase in proton gradient - electron transport and ATP synthesis will stop |
|
|
uncoupling agents
|
increased permeability of membrane -> decreased proton gradient and INCREASED O2 consumption
ATP synthesis stops, electron transport continues -> HEAT e.g. 2,4 DNP, asprin, thermogenin (Brown fat) |
|
|
chronic granulomatous disease
|
NADPH oxidase deficiency - can't make H2O2
can't fight catalse producing bugs (S. Aureus, aspergillis) because they neutralized H2O2 |
|
|
G6PD deficiency
|
X linked recessive
can't produce NADPH needed to reduced glutathione for protection against free radicals G6PD especially important in RBC because no mitochondria see heinz bodies and bite cells |
|
|
heinz bodies
|
precipiated OXIDIZED hemoglobin within RBC
see with G6PD deficiency |
|
|
Bite cells
|
result from phagocytic removal of heinz bodies by macrophages
|
|
|
essential fructosuria
|
defect in fructokinase
autosomal recessive benign - see fructose in blood and urine |
|
|
fructose intolerance
|
hereditary deficiency of aldolase B
autosomal recessive - see increase in F1P -> decreased avialble phosphate inhibits glyocogenlolysis and gluconeogenesis ---> hypoglycemia, jaundice, cirrhosis, vomiting treat with decrease fructose and sucrose intake |
|
|
glactokinase deficiency
|
galactitol accumulets
auto recessive see galactose in blood and urine, infantile cataracts - mild symptoms may present as inability to tract objects or social smile in infant |
|
|
classic glacotsemia
|
absence of glactose 1 phosphate uridyltransferase
auto recessive accumulation of toxic substances - glactitol failure to thrive, jaundice, hepatomegally, cataracts, retardation eliminate galactose and lactose from diet |
|
|
sorbitol
|
converted from glucose via aldose reducase
if no sorbitol dehydrogenase in the cell to convert sorbitol to fructose, then sorbtol will build up -> osmotic damage |
|
|
tissues suseptable to sorbitol osmotic damage
|
schwann cells, lens, retina, kidneys
don't have sorbitol dehydrogenase (liver, ovaries, seminal vesicles have both enzymes) |
|
|
essential amino acids
|
gluconeoginic: MEt, Val, Arg, His
Ketogenic: Leu, Lys Both: Ile, Phe, Thr, Trp |
|
|
amino acids important in growth
|
Arg and His
|
|
|
transport of ammonium occurs through what amino acid
|
alanine (from muscle to liver)
|
|
|
rale limiting step of urea cycle
|
carbamoyl phosphate synthetase I
|
|
|
hyperammonemia
|
-> ammonia intoxication -> tremor, slurred speech, tiredness, vomiting, cerebral edema, vision blurring
excess NH4+ depletes alpha-ketoglutarate -> inhibits TCA cycle treat with limiting protein, beonzoate, or phenylbutyrate |
|
|
most common urea cycle disorder
|
ornithine transcarbamoylase deficiency
X linked recessive body cannot eliminate ammonia see back up of carbamoyl phsphatase which is converted to orotic acid look for high orotic acid in blood and urine, decreased BUN, and increased ammonia |
|
|
glycine derivative
|
prophyrin, heme
|
|
|
arginine derivatives
|
creatine, urea, nitric oxide
|
|
|
glutamate derivatives
|
GABA
Glutathione |
|
|
tryptophan derivatives
|
niacin -> NAD
serotinin -> meatonin |
|
|
phenylketonuria (PKU)
|
decreased phenylalanine hydroxylase OR decreased tetrahydrobiopterin cofactor
cannot convert phenylalanine to tyrosine (makes tyrosine an essential AA) excess phenylalaine leads to mental retardation, growth restriction, siezures, MUSTY body odor phenylketones in urine - phenylacetate, phenyllactate, phenlypyruvate control with diet (especially during pregnancy - Maternal PKU) |
|
|
alkapotonuria
|
deficienct in homogentistic acid oxidase
auto recessive dark connective tissue, brow sclera, urine turns black, arthralgias |
|
|
albinism
|
deficient tyrosinase or tyrosine transporters
defective melanin production can result from lack of migration of neural crest cells |
|
|
homocystinuria (3 forms)
|
auto recessive
3 forms: 1. cystathionase synthase def (treatment by decreasing methionine and increased cysteine and B12 and folate in diet) 2. decreased affinity of cystathionine synthase for pyridoxal phosphate (treat with lots of B6) 3. homocystine methyltransferase deficiency **in all 3 see increased homocysteinine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis |
|
|
cystinuria
|
defect in tubular renal amino acid transporters for cysteine, ornithine, lysine, and arginine
excess cystine ->cystine kidney stones treat with acetocolamide to alk the urine |
|
|
maple syrup urine disease
|
blocked degen of branched amino acids (Ill, Leu, Val)
decreased alpha ketoacid dehydrogenase CNS defects, mental retardation, death urine smells like maple syrup "I Love Vermont" maple syrup from branched maple trees |
|
|
Hartnup disease
|
leads to pellagra (diarrhea, dermatitis, dementia)
inability to reabsorb tryptophan in urine and decreases absorption in the gut no niacin from tryptophan |
|
|
glycogen phosphorylase kinase
|
activated by glucagon/epinephrine and Ca++/calmodulin
converts glygocgen phosphorylase (rate limiting enzyme) to active form for glycogenolysis |
|
|
glycogen storage diseases
|
Very Poor Carbohydrate Metabolism
Von Gierke (type 1) Pompe's (type II) Cori's (type III) McArdle (type V) |
|
|
Von Gierke's disease
|
deficient glucose 6-phosphatase
see hypoglacemia, increased glycogen, increased lacate, hepatomegaly |
|
|
pompe's disease
|
lack lysosomal alpha 1,4 glucosidase (acid maltase)
see cardiomegaly, systemic findings -> death |
|
|
Cori's disease
|
lack debranching enzyme
increased limit dextran mild form of type 1 (von gierke) with NORMAL LACTATE levels |
|
|
McArdles disease
|
lack skeletal muscle glycogen phosphorylase
increased glycogen in muscle, cannot break it painful cramps, myoglobinuria during strenuous exercise McArdles = Muscle |
|
|
most common lysosomal storage disease
|
gaucher's disease - deficienct beta-clucocerebroside -> increased glucocerebroside
hepatosplenomegaly, asceptic necrosis of femur see gaucher cells which are macrophages that look like crumpled tissue |
|
|
Fabry disease
|
lack alpha galactosidase A
x-linked rec accumulates ceramide trihexoside peripheral neuropathy of hands and feet, angiokeratomas, CV/Renal disease |
|
|
Niemann Pick disease
|
lack sphingomyelinase
auto rec build up sphingomyelin get neurodegeneration, hepatosplenomegaly, foam cells , cherry red spot on macula |
|
|
tay sachs disease
|
lack hexosamindase A
auto rec build up GM3 ganglioside get neurodegeneration, dev delay, cherry red spot on macula, lysosomes with onion skin NO hepatosplenomegaly |
|
|
niemann pick vs tay sachs
|
niemann pick - hepatosplenomegaly
|
|
|
krabbe's disease
|
lack galactocerebrosidase
auto rec galactocerebroside build up peripheral neuropathy, developmental delay, optic atrophy, globoid cells |
|
|
Metachromatic leukodystrophy
|
lack arylsulfatase A
auto rec build up cerebroside sulfate central and peripheral demyelination - ataxia, dementia |
|
|
hurlers syndrome
|
mucopolysaccharidosis
lack alpha L iduronidase auto rec build up heparan and dermatan sulfate developmental delay, garoylism, airway obstruction, corneal clouding |
|
|
hunter's syndrome
|
mucopolysaccharadosis
lack iduronate sulfatase build up heparan and dermatin sulfate X linked rec mild hurlers + aggressive behavior, no corneal clouding Hunters see clearly and aim for the X |
|
|
carnitine deficiency
|
inability to transport small chain fatty acids into mitochondria -> accumulation
CARnitine is CARnage of fatty acids weakness, hypotonia, hypoketotic hyperglcemia |
|
|
acyl-CoA dehydrogenase def
|
increased dicarcboxylic acids
decreased glucose and keytones |
|
|
when are ketone bodies relied on for energy by brain and heart?
|
starvation after day 3
|
|
|
when does the body start using FFA as main energy source?
|
starvation between days 1-3 after glycogen stores run out
|
|
|
when do glycogen reserves deplete usually
|
after day 1 of starvation
|
|
|
chylomicron apolipoprotines
|
B-48, A-IV, C-II, E
|
|
|
VLDL apolipoprotines
|
B-100, C-II, and E
|
|
|
IDL apolipoprotines
|
B-100 and E
|
|
|
LDL apolipoprotines
|
B-100
|
|
|
what ware the kinds of apolipoprotines
|
A-I - Activates LCAT
B-100 - Binds LDL receptor, mediates VLDL secretion C-II Cofactor for lipoprotein lipase B-48 - mediates chylomicrosecretion E - mediates extra remnant uptake |
|
|
LCAT
|
lecithin cholesterol acyltransferase - catalyze esterification of cholesterol
|
|
|
CETP
|
cholesterol ester transfer protein
mediates transfer of choelsterol esters to other lipoproteins |
|
|
hyperhylomicronemia
|
familial dyslipidemia type 1
see increased chylomicrons, elevated TG and cholesterol due to lipoprotein lipase deficiency or altered apoC-II --> pancreatities, hepatoslenomegaly, xanthomas NO RISK FOR ATHEROSCLEROSIS |
|
|
familial hypercholesterolemia
|
autosomal dominant familial dyslipidemia type IIa
increased LDL and cholesterol due to decreased LDL receptors accelerated atherosclerosis, xanthomas, corneal arcus |
|
|
hypertriglyceridemia
|
famililal dyslipidemia
increased VLDL and TGs due to overproduction of VLDL -> panceratitis |
|
|
abeta-lipoproteinema
|
can't synthesize liporoteins due to deficiencies in apoB-100 and apoB-48
auto recessive accumulation within enterocytes see failure to thrive, steatorrhea, acanthocytosis, ataxia, nigh blindness |
