First Aid Biochem Flashcards
What are the purines/pyrimadines
Pure As 2 Gold rings
C,U,T the py
Pyrimidine and Purine synthesis fuckups
Leflunomide, Methotrexate/Trimethoprim/pyrimethanmine, F-5U, 6-Mp, Ribavirin, Hydroxyurea
Pyrimidine fuck up
Leflunomide: messes up dihydroorate dehydrogenase (Carbomyl phosphate –> orotic acid)
MTX/TMP: messes up dihydrofolate reductase
F-5U: messes up thymidine synthesis
Purine fuck ups
6-Mp: messes with PRPP –> IMP
Ribavirn: fucks up IMP –> GMP
Hydroxyurea: fucks up both pyrimidine and purine
Adenosine Deaminase Deficiency (ADA)
whats the inheritance
major cause of SCID
you cant degrade adenosine into Inosine —> TOO MUCH ATP
leads to toxicity in Lymphocytes (no B or T cells)
AR
Lesch-Nyhan syndrome
whats the deficiency and Tx
Defect in Purine synthesis
Lack of HGPRT: you cant convert
Hypoxanthine –> IMP / Guanine –>GMP
results in Excess uric Acid
Tx- Allopurinol or Febuxostat
DNa replication functions
Single Stranded binding protiens / Primase / DNA polymerase III / Exonuclease / DNA polymerase I / DNA Topoisomerase / DNA ligase / DNA helicase
SSBPs: prevent single strands from reannealing (fusing)
Primase: Creates RNA primer for DNA polymerase to start replication on
DNA Polymerase III: Prokaryotes only. 5-3 synthesis
Exonuclease: proofreads
DNA Polymerase I: removes primer
DNA Topoisomerases: removes supercoils by nicking the dna
DNA ligase: seals the okazaki fragments by making phosphodiester bonds
DNA Helicase: Unwinds DNA
Which drugs block DNA topoisomerase (gyrase)
Flouroquinolones
Mismatch repair SS
deficiency leads to what dz?
presentation
fixes AG CT repairs
Lynch (HNPCC)
microstellate instability
Base excision repair SS
what causes the damage
Repairs damaged bases (toxic deamination-oxygen radicals) via glycoslyase
DNA polymerase-b fills the gap
Apurinic/Apyrimidinc site
Nucleotide excision Repair SS
defective repair leads to
Endonucleases cleave off damaged bases.
repairs bulky helix-distorting lesions
defective in Xeroderma pigmentosum (pyrimidine dimers) due to UV-B
Non homologous end joining Repair DS
whats the damage caused by?
Repair Double Strand breaks
ionizing radiation/ free radicals
What are the RNA polymerases in Eukaryotes?
RNA Polymerase I: rRNA
RNA polymerase II: mRNA (biggest)
RNA Polymerase III: tRNA (three)
What toxin is found in Death cap mushroom and how does it work?
inactivates RNA polymerase II (mRNA)
causes hepatotoxicity
How does rifampin work?
Inhibits RNA Polymerase in prokaryotes
How is RNA processed from hnRNA to mRNA
1) Capped at 5’ end w/ 7-methylgaunosine cap
2) Tailed via polyadenation Poly-A tail
3) Spliced (spliceosome) snRNPs
Function of Rough ER
Site of Synthesis of secretory proteins & N-linked oligosacharide
-Nissl Bodies in neurons
Funciton of Smooth ER
which cells have a ton?
Steroid synthesis and detox of drugs and poison
(liver hepatocytes and steroid hormones of adrenal cortex)
Kartageners syndrome
whats fucked up? whats the defect
presentation
a Primary Cilia fuck up.
immotile cilia due to dynein arm defect
Infertile, bronchiectasis, Situs inversus
What are the precursor proteins in Collagen
Glycine - Proline - Lysine
if you have scurvy what is the mess up
Deficient in Vit. C so you cant properly hydroxylize Proline and lysine
Whats wrong in Osteogenisis Imperfecta
why do you get blue sclera?
You have trouble forming the Triple helix of Procollagen
Choroidal veins
Whats wrong in Ehlers Danlos
You have problem with cleaving procollagen at N and C terminals
and Cross-linking
Whats up with Menkes Dz
presentation
X-linked
Impaired copper absorption
defective Menkes protein ATP7A
-kinky hair, growth retard, hypotonia
what are the wrinkles of aging due to?
Decreased collagen and elastin
Polymerase chain Reaction (PCR)
what are the steps
used to Amplify a desired fragment of DNA
diagnostic tool for HIV, herpes, encephalitis
1) Denature DNA with heat. along with 2 DNA primers beginning and end
2) Annealing: now that DNA is separated, it cools and the primers anneal to the strands
3) Elongation
Blotting - Southern Blot
DNA Sample
1) cleaved to smaller pieces then separted on gel electrophoresis then moved to a filter
2) Filter is exposed to radiolabed DNA probe that recognizes and anneals to the small pieces from 1
3) you end up with double stranded labeled pieve of DNA
Blotting - Northern Blot
Similar to DNA blot but you use RNA
useful for mRNA levels & Gene expression
Blotting - Western Blot
Protein is used.
Labeled Antibody is used to bind relevant protein
confirmatory test for HIV after ELISA
Fluorescence in Situ Hybridization (FISH)
fluorescent DNA or RNA probe binds to specifice gene site of interest on chromosoes
can tell- microdeltion, translocation, dubplication
detect location
Genetic terms
Pleiotropy / linkage disequillibrium / mosaicism / uniparental disomy
Pleiotropy: one gene contributes to multple phenotypic effects
Linkage diseq: tendance for certain alleles at 2 linked loci to occur together more or less than expected by chance
Mosaicisim: presence of genetically distinct cell lines in the same individual ie Mccune-albright
Uniparental disomy: offspring recieves 2 copies of chromosome from 1 parent and no copies from the other. Correct # of chromosomes (recessive disorder when only one parent is a carrier)
Whats Mccune Albright
mutation affecting the G- protien
Cafe au lait, fibrous dysplasia, precocious puberty, endocrine abnormalities
Downsyndrome (21)
presentation, what is a risk factor leading to it?
what are some comorbidities of Downs
First trimester Ultrasound
2nd trimester quad screen
Flat face, epicanthal folds, single palmar crease
- incr. maternal age
- Alzheimers, Hirschprung, Duodenal atresia, Congenital heart anomalies
- incr. nuchal transluncency
-incr. B-hcg, inhibin A / decr. AFP, estriol
Edwards (18)
presentation screening?
Rocker-bottom feet, small jaw, lowset ears, clenched hand overlapping fingers.
-everything is decreased AFP, b-hCG, estriol, inhibin A
Patau syndrome (13)
Rockerbody feet, cleft lip/Palate, holoProsencephaly
Polydactyl
Cri-du-chat (chromosome deletion)
whats the deletion
Crying/mewing like a cat
Microdeletion of short arm of Chromosome 5
microencephaly/ VSD
Williams syndrome (chromosome deletion)
delation of chromosome 7
elvin facies, hypercalcemia
22q11 deletions
CATCH-22
Cleft palate, Abnormal face, Thymic dysplasia (T-cell deficiency) Cardiac defects, Hypocalcemia (no parathyroid)
fuck up of the 3rd and 4th branchial pouch
Digeorge- thymic, parathyroid, cardiac defects (no face)
Velocardiofacial syndrome- palate, facial, cardiac defects (no parathyroid probs)
Trinucleotide repeats
Try hunting for my fried egg
EX Gf First Aid Helped Ace My Test
Vit A
usues? Deficiency? Toxicity?
part of Visual pigiments, differentation of epithelial cells to special tissue: pancreatic cells, mucus secreting, prevents squamous metaplasia
-Wrinkles and Acne
Deficiency: Night blindness, dry scaly skin, Bitot spots (cornea of eye)
-teratogen, alopecia, dry skin
B1 Thiamine
deficiency?
Cofactor of dehydrogenase enzymes
*think ATP*
A-keto glutarate, transketolase, pyruvate dehydrogenase
-Beriberi / Wernicke korsakoff. seen in alcoholics
imparied glucose breakdown
B2 Riboflavin
deficiency
FAD
- Cheilosis (inflam of lips and scaling of mouth)
- Corneal vasculation
Vit B3 (Niacin)
wheres it derived from? deficiency? toxicity
NAD,
derived from Tryptophan,
-Pellagra: 3D’s- Diarrhea, Dementia, Dermatitis(c3/c4) necklace rash
-toxicity: flushing
which vitamins arent in breast milk
D & K
Kwashiorkor
Malnutrition due to Protein deficiency
Lil kid with Fat belly (edema due to decr. oncotic pressur), Fat liver, and anemia
Marasmus
Malnutrition of Protein & Calories
Super skinny muscle wasting
Whats Fomepizole and how does it work
what is it an antidote for?
It inhibits Alcohol dehydrogenase
Methanol/ethylene glycol poisoning
whats Disulfram and moa
Inibits Acetylaldehyde dehydrogenase
Acetylaldehyde buildup is the reason for hangover symptoms
what does the buildup of NADH lead to?
build up of lactate (Lactic acidosis) and Malate (hypoglycemia)
Pyruvate —NADH–> Lactate
Oxaloacetate —NADH–> Malate
whats the only source of energy for RBC
Glycolysis
Pyruvate kinase deficiency
means you cant make pyruvate in glycolysis so you cant form ATP which means RBCs die via Hemolytic anemia
What cofactors are needed for pyruvate dehydrogenase. whats the purpose of this enzyme
Pyruvate —-Dehydrogenase–> Acetyl CoA
TLC For Nancy
Thiamine, Lipoic acid, Co A, Favin (b2), NAD (b3)
pyruvate dehydrogenase deficiency
how do you treat it?
cant turn Pyruvate into Acetyl Coa
So you get a build up of pyruvate that get turned into Lactate acid (
Lactic acidosis & incr. serum Alanine
Ketogenic nutrients Lysine/Leucine
What does arsenic poisoning due?
fucks up Lipoic acid so no more pyruvate dehydrogenase
Garlic breath
Pyruvate metabolism
what all does pyruvate turn into and its enzymes
Pyruvate
—-Alanine transaminase–>Alanine
—-Lactate dehydrogenase—>Lactate
_______
in mitochondira
—-Pyruvate dehydrogenase–>ACetyl Coa
—-Pyruvate carboxylase—>Oxaloacetate
Main funciton of TCA cycle
generate fuel for ATP synthesis
What is citrate used for?
shuttles Acetyl CoA out of mitochondria for Fatty acid synthesis
Electron transport chain/Ox phos
function? how are they transported?
Take the 3NADH and 1FADH from TCA cyle and generate ATP
NADH transported via malate-aspartate shuttle/ Glycerol 3 phosphate shuttle
FADH complex II
Electron Transport inhibitors
Moa?
inhibit electron transport flow (causing decr. in proton gradient)
blocks ATP synthesis
RotenONE fucks up complex ONE (NADH dehydrogenase)
An-3-mycin A (antiymycin) fucks up Complex 3 (Cytochrome Bc)
CO/CN fucks up 4 (Cytochrome C)
whats the antidote to Cyanide poisoning?
Thiosulfate
ATP synthase inhibitors
Uncoupling agents?
this directly inhibits mitochondrial ATP synthse
Oligomycin
__________________
decr proton gradient and incr O2 consumption Produces Heat
2,4 Dinitrophenol, thermogenin in brown fat
Glucose Transporters
fuctions of GLUT 1-4 and locatoin
Glut 1: normal uptake at basal layer / many places
Glut 2: low affinity glucose uptake / hepatocytes, pancratic B cells,
Glut 3: brain neurons
Glut 4: insulin controlled/ Muscles myocytes,
HMP (hexose-monophosphate) shunt
function? reactions involcved
provides source of NADPH from glucose-6-P
it also creates Ribose for Nucleotide synthesis
________
G6P —G6PD—> NADPH + Ribose
function of NADPH
required for reductive reactions:
glutathione, fatty acid and cholesterol synthesis
G6PD deficiency
what does it lead to?
what will you see on smear?
failure to produce NADPH
without NADPH you cant keep glutathione reduced.
without Glutathione you cant detoxify free radicals
___
Hemolytic anemia since RBCs cant handle oxidative stress
____
Heinz bodies (denatured Hb inside RBC)
Bite cells due to splenic macrophages removing Heinz bodies
Essential fructosuria
whats the defect. what is it? what are symptoms
Fructokinase defect - you cant break down fructose
Benign since fructose isnt trapped in cells
symptoms: fructose appears in blood and urine
Fructose intolerance
whats the deficiency? what cant you break down?
whats the huge fuck up? when do symptoms present?
Aldolase B -
you cant break down Fructose-1-P (it accumulates)
causes decrease in available phosphate
*** inhibits Glycogenolysis + Gluconeogenis***
after eating fruit, juice, or honey
Galactokinase deficiency
what does it lead to?
cant turn Galactose into Galactose-1-P
galactosemia, infantile cataracts,
incr. Galactisol (accumulates in lens of eye)
failure to develop social smile
Classic Galactosemia
what enzyme is deficient
Galactose-1-P uridyltransferase
cataracts (due to Galactisol), MR, E. coli spsis
phosphate deficiency
Sorbitol metabolism
function? what happens if you get too much sorbitol buildup and where?
Alternative pathway of trapping glucose in the cell is by converting it to its alchol form (sorbitol)
Glucose —Aldose reductase–> Sorbitol
Sorbitol —Sorbitol dehydrog–>fructose
____
if you dont have sorbitol dehydrogenase then sorbitol will accumulate. its osmotically active which can cause damage. Schwann cells, retina, and kidney dont have it.
what sugars is lactose made of?
Glucose and Galactose
Lactase deficiency
where does lactase work? 2 ways to get it?
how do you test?
Lactose intolerance
functions on the brush border to digest lactose
1) age dependent decline of lactase 2) loss of brush border
- incr. hydrogen with lactose hydrogen breath test
Urea cycle
function? where does the excess Nitrogen go?
whats a big main function
Amino Acid catabolism that results in formation of metabolites used in TCA cylce for ATP synthesis
-turned int Urea for pee
way to get rid of ammonia
Hyperammmoniemia
what are the 2 deficiencies
N-acetylglutamate Synthase
Carbamoyl phosphate synthetase I deficiency
Ornithine Transcarbamylase deficiency
findings
Urea cylce disorder
Body cant eliminate ammonia
Excess Carbamoyl phosphate —-> Orotic acid (pyrimidine synthesis)
Incr. Orotic acid/ decr. BUN/ hyperammonemia
Ammonia transport
how is it transported from tissues to be excreted
glutamate and alanine
Pyruvate transport (glucose-alanine cycle)
Hartnup Disease
cant transport Tryptophan –> means you get a deficiency in Serotonin and Niacin
lack of niacin–> Pallagra smptoms
What are the amino acid derivatives
Phylalanine:Tyrosine (thyroxine), DOPA(melanin), dopamine, NE, epi
Tryptophan: Niacin (NAD/NADP), Serotonin (melotonin)
Histidine: Histamine
Glycine: Protoporphyrin, Heme
Glutamate: GABA, Glutathione
Aspargine: Urea, Creatine, NO
PKU
whats the deficiency? presentation? tx? what must they avoid
inability to breakdown Phenyalanine
decr. Phenylalanine hydroxylase/ tetrahydrobiopterin
incr. pheynlalanine levels (duh)–> excess phenylketones in urine
- MR, growth retard, siezure, fair skin, eczema, musty body odor
tx- You gotta remove phenylalanine from diet and Incr. Tyrosine to bypass the defect.
must avoid aspartame (artificial sweetener that contains phenylalanine)
Maple syrup urine dz
whats decreased? presentation? tx?
Decreased degredation of branced amino acids
Isoleucine Leucine Valine
(I love vermont Maple syrup Branches1)
Decr. alpha keto acid dehydrogenase
- CNS defects, urine smells like maple/burnt sugar
- restriction of ILV from diet. Thiamine supplement
Alkaptonuria
finding
congenital deficiency of homogentisate oxidase
Cant turn Tyrosine into Fumarate
-Bluish-black skin & sclera / arthritis
pee turns dark after exposure to air
Homocystinuria
what causes it? presentaiton
Build up of homocystine
due to lack of b6 (pyridoxine) or b12(cobalamin)
marfans/vessel damage
walk thru Glycogenolysis & glycogenesis
Glycogenolysis
Glucagon or Epi attaches to muscle or liver. Activates Adenylase Cyclase which incr. cAMP. this stimulates Protein Kinase A which stimulates Glycogenphosphorylase kinase –> Glycogen phosphorylase —> breaks down glycogen
Glycogenesis
Insulin binds to muscle and liver via tyrosine kinase
stimulates protein phosphorylase –> stimulates Glycogen synthase –> makes glycogen
Glycogen storage dz
Very poor Carb metabolism
Type 1: Von Gierks dz
Type 2: Pompe dz
Type 3: Cori dz
Type 5: McArdle dz
Von Gierke Dz
what enzyme is deficient? findings
Type 1 glycogen Storage dz
Glucose-6-phosphatase
Cant turn Glucose into G6P
- severe fasting hypoglycemia, increased glycogen in liver
- body relies on fat and protein metabolism so
Incr. triglycerides, blood lactate, and uric acid (gout)
Pompe dz
whats special bout this one
Type 2 glycogen storage dz
Lysosomal
Pompe trashes the Pump (severe heart problems)
Cori dz
deficiency
glycogen storage dz Type 3
debranching enzyme A-1,6 glucosidase
normal lactate levels
McArdle dz
deficiency? what happens when they exercise?
type 5 glycogen storage dz
glycogen phosphorylase*** / ***muscle phosphorylase
Incr. glyocen in Muslce becase you cant break it down w/o glycogen phosphorylase
Muscle cramps, Myoglobinuria (red urine) with excercise / 2nd wind phenomenon
Lysosomal storage dz’s
list em
Sphingolipidoses
Fabry, Gaucher, Niemann-Pick, Tay-Sachs, Krabbe, Metachromatic leukodystrophy
Mucopolysaccharidoses
Hurler, Hunter
Fabry Dz
Deficient enzyme? and build up of what
lysosomal storage dz
Triad: Periph neuropathy, angiokeratomas, hypohidrosis (diminished sweating)
A-galactosidase A / Ceramide trihexoside
Gaucher dz
deficient in? what builds up? findings
lysosomal storage dz
B-glucocerebrosidase / Glucocerebroside
cells look like crinkled tissue paper.
Hepatosplenomegaly, aseptic necrosis of femur
Niemann-Pick dz
deficient? build up? findings
Lysosomal storage dz
Sphingomyelinase / Sphingomyelin
neurodegeneration/ cherry red macula / Hepatosplenamegaly
Tay-sachs dz
deficient? build up? findings
lysosomal storage dz
Hexosaminidase A / GM2 ganglioside
Cherry red on macula, onion skin lysosomes, (no hepatosplenomegaly)
Krabbe dz
deficient? build up? findings
lysosomal storage dz
B-galactocidase / Galactocidase + psychosin
Optic atrophy, destroys myelin sheath
Metachromatic leukodystrophy
deficient? build up? findings
Lysosomal Storage do / demyelinating do
Arylsulfatase A / Sulfatides
destroys myelin, ataxia, dementia
Hurler Syndrome
deficiency? build up? findings?
lysosomal storage dz - Gargoylism
A-L-iduronidase / heparan & dermatan sulfate
Gargoylism, corneal clouding
Hunter Syndrome
deficiency? buildup? findings
lysosomal storage dz
Iduronate sulfatase / heparan & dermatan sulfate
aggresive behavior, no corneal clouding
what is needed in fatty acid Synthesis
whats the end product?
Citrate
from the mitochondria “SYtrate”
palmitate
what is needed for Fatty acid degredation
what mechanism is used and where?
deficiency of transporter?
Carnitine
B-oxidation in the mitochondria
Carnitine deficiency- inherited defct in transport of LCFA into mitochondria
–>weakness, hypotonia, hypoketoic hypoglycemia
what happens in alcoholism (excess NADH)
Prolonged starvation
excess NADH which shunts
pyruvate–>lactate
Oxaloacetate–>malate
________
oxaloacetate gets used up by gluconeogeneisis
both cause a build up of acetyl-CoA which shunts glucose and FFA to Ketone bodies
What are the ketone bodies?
Acetone, Acetoacetate , B-hydroxybutyrate
Acetone gets breathed off
B-hydroxy –> Acetoacetate which gets converted to acetyl coa (used for TCA cylce to make ATP) in tissues
Dietary fuel
kcal of protein, carb, fat, alcohol
1g of protein/carb: 4 kcal
1g of fat: 9 kcal
1g of alcohol: 7kcal
what happens after a fed state?
Insuline stimulates storage of lipids, proteins, glycogen
via Glycogen synthase
what happens in a fasting state (between meals)
Hepatic glycogenolysis
via glucagon & epinephrine stimulation
glycogen phosphorylase
Cholesterol
function? rate limiting step?
used to maintain cell membrane,
synthesize bile acid, steroids and Vit D.
HMG-CoA reductase is rate limiting
