First Aid Biochem Flashcards
1
Q
What are the purines/pyrimadines
A
Pure As 2 Gold rings
C,U,T the py
2
Q
Pyrimidine and Purine synthesis fuckups
Leflunomide, Methotrexate/Trimethoprim/pyrimethanmine, F-5U, 6-Mp, Ribavirin, Hydroxyurea
A
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
3
Q
Adenosine Deaminase Deficiency (ADA)
whats the inheritance
A
major cause of SCID
you cant degrade adenosine into Inosine —> TOO MUCH ATP
leads to toxicity in Lymphocytes (no B or T cells)
AR
4
Q
Lesch-Nyhan syndrome
whats the deficiency and Tx
A
Defect in Purine synthesis
Lack of HGPRT: you cant convert
Hypoxanthine –> IMP / Guanine –>GMP
results in Excess uric Acid
Tx- Allopurinol or Febuxostat
5
Q
DNa replication functions
Single Stranded binding protiens / Primase / DNA polymerase III / Exonuclease / DNA polymerase I / DNA Topoisomerase / DNA ligase / DNA helicase
A
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
6
Q
Which drugs block DNA topoisomerase (gyrase)
A
Flouroquinolones
7
Q
Mismatch repair SS
deficiency leads to what dz?
presentation
A
fixes AG CT repairs
Lynch (HNPCC)
microstellate instability
8
Q
Base excision repair SS
what causes the damage
A
Repairs damaged bases (toxic deamination-oxygen radicals) via glycoslyase
DNA polymerase-b fills the gap
Apurinic/Apyrimidinc site
9
Q
Nucleotide excision Repair SS
defective repair leads to
A
Endonucleases cleave off damaged bases.
repairs bulky helix-distorting lesions
defective in Xeroderma pigmentosum (pyrimidine dimers) due to UV-B
10
Q
Non homologous end joining Repair DS
whats the damage caused by?
A
Repair Double Strand breaks
ionizing radiation/ free radicals
11
Q
What are the RNA polymerases in Eukaryotes?
A
RNA Polymerase I: rRNA
RNA polymerase II: mRNA (biggest)
RNA Polymerase III: tRNA (three)
12
Q
What toxin is found in Death cap mushroom and how does it work?
A
inactivates RNA polymerase II (mRNA)
causes hepatotoxicity
13
Q
How does rifampin work?
A
Inhibits RNA Polymerase in prokaryotes
14
Q
How is RNA processed from hnRNA to mRNA
A
1) Capped at 5’ end w/ 7-methylgaunosine cap
2) Tailed via polyadenation Poly-A tail
3) Spliced (spliceosome) snRNPs
15
Q
Function of Rough ER
A
Site of Synthesis of secretory proteins & N-linked oligosacharide
-Nissl Bodies in neurons
16
Q
Funciton of Smooth ER
which cells have a ton?
A
Steroid synthesis and detox of drugs and poison
(liver hepatocytes and steroid hormones of adrenal cortex)
17
Q
Kartageners syndrome
whats fucked up? whats the defect
presentation
A
a Primary Cilia fuck up.
immotile cilia due to dynein arm defect
Infertile, bronchiectasis, Situs inversus
18
Q
What are the precursor proteins in Collagen
A
Glycine - Proline - Lysine
19
Q
if you have scurvy what is the mess up
A
Deficient in Vit. C so you cant properly hydroxylize Proline and lysine
20
Q
Whats wrong in Osteogenisis Imperfecta
why do you get blue sclera?
A
You have trouble forming the Triple helix of Procollagen
Choroidal veins
21
Q
Whats wrong in Ehlers Danlos
A
You have problem with cleaving procollagen at N and C terminals
and Cross-linking
22
Q
Whats up with Menkes Dz
presentation
A
X-linked
Impaired copper absorption
defective Menkes protein ATP7A
-kinky hair, growth retard, hypotonia
23
Q
what are the wrinkles of aging due to?
A
Decreased collagen and elastin
24
Q
Polymerase chain Reaction (PCR)
what are the steps
A
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
25
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
26
Blotting - Northern Blot
Similar to DNA blot but you use **RNA**
useful for **mRNA** levels & **Gene expression**
27
Blotting - Western Blot
**Protein** is used.
Labeled Antibody is used to bind relevant protein
confirmatory test for **HIV** after **ELISA**
28
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**
29
_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)
30
Whats Mccune Albright
mutation affecting the G- protien
Cafe au lait, fibrous dysplasia, precocious puberty, endocrine abnormalities
31
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
32
_Edwards (18)_
presentation screening?
**Rocker-bottom feet,** small jaw, lowset ears, clenched hand overlapping fingers.
-everything is decreased AFP, b-hCG, estriol, inhibin A
33
Patau syndrome (13)
Rockerbody feet, cleft li**p/P**alate, holo**P**rosencephaly
**P**olydactyl
34
_Cri-du-chat_ (chromosome deletion)
whats the deletion
Crying/**mewing** like a cat
Microdeletion of short arm of **Chromosome** **5**
microencephaly/ VSD
35
_Williams syndrome_ (chromosome deletion)
delation of **chromosome 7**
**elvin facies**, hypercalcemia
36
22q11 deletions
CATCH-22
**C**left palate, **A**bnormal face, **T**hymic dysplasia (T-cell deficiency) **C**ardiac defects, **H**ypocalcemia (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)
37
Trinucleotide repeats
**Try** **hunting** for **my fried egg**
E**X** **G**f **F**irst **A**id **H**elped **A**ce **M**y **T**est
38
_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 **A**cne
Deficiency: **Night blindness,** dry scaly skin, **Bitot spots** (cornea of eye)
-**teratogen,** alopecia, dry skin
39
**B1 Thiamine**
deficiency?
Cofactor of **dehydrogenase enzymes**
**\***think ATP\*
**A-keto glutarate, transketolase, pyruvate dehydrogenase**
**-**Beriberi / Wernicke korsakoff. seen in alcoholics
**imparied glucose breakdown**
40
B2 Riboflavin
deficiency
FAD
- **C**heilosis (inflam of lips and scaling of mouth)
- **C**orneal vasculation
41
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
42
which vitamins arent in breast milk
D & K
43
_Kwashiorkor_
Malnutrition due to **Protein deficiency**
Lil kid with **Fat belly** (edema due to decr. oncotic pressur), **Fat liver**, and anemia
44
_Marasmus_
Malnutrition of **Protein** & **Calories**
Super skinny muscle wasting
45
Whats **Fomepizole** and how does it work
what is it an antidote for?
It inhibits **Alcohol dehydrogenase**
**Methanol/ethylene glycol** poisoning
46
whats **Disulfram** and moa
Inibits **Acetylaldehyde dehydrogenase**
Acetylaldehyde buildup is the reason for hangover symptoms
47
what does the buildup of NADH lead to?
build up of **lactate** (*Lactic acidosis)* and **Malate** (hypoglycemia)
Pyruvate ---NADH--\> Lactate
Oxaloacetate ---NADH--\> Malate
48
whats the only source of energy for RBC
Glycolysis
49
Pyruvate kinase deficiency
means you cant make **pyruvate** in glycolysis so you cant form ATP which means RBCs die via Hemolytic anemia
50
What cofactors are needed for **pyruvate dehydrogenase**. whats the purpose of this enzyme
Pyruvate ----Dehydrogenase--\> Acetyl CoA
**TLC** **F**or **N**ancy
Thiamine, Lipoic acid, Co A, Favin (b2), NAD (b3)
51
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**
52
What does **arsenic poisoning** due?
fucks up **Lipoic acid** so no more *pyruvate dehydrogenase*
## Footnote
**Garlic breath**
53
_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
54
Main funciton of TCA cycle
generate fuel for **ATP synthesis**
55
What is **citrate** used for?
shuttles Acetyl CoA out of mitochondria for Fatty acid synthesis
56
Electron transport chain/Ox phos
function? how are they transported?
Take the **3***NADH* and **1***FADH* from _TCA cyle_ and generate **ATP**
NADH transported via **malate-aspartate** shuttle/ **Glycerol 3 phosphate** shuttle
FADH complex II
57
Electron Transport inhibitors
Moa?
inhibit electron transport flow (causing decr. in proton gradient)
**blocks ATP synthesis**
_Roten**ONE**_ fucks up complex **ONE** (NADH dehydrogenase)
_An-**3**-mycin A_ (antiymycin) fucks up Complex **3** (Cytochrome Bc)
**CO/CN** fucks up **4** (Cytochrome C)
58
whats the antidote to Cyanide poisoning?
**Thiosulfate**
59
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**
60
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,
61
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
62
function of NADPH
required for reductive reactions:
**glutathione,** fatty acid and cholesterol synthesis
63
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
64
_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
65
**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
66
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**
67
Classic Galactosemia
what enzyme is deficient
**Galactose-1-P uridyltransferase**
cataracts (due to Galactisol), MR, E. coli spsis
phosphate deficiency
68
_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.
69
what sugars is lactose made of?
Glucose and Galactose
70
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
71
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**
72
Hyperammmoniemia
what are the 2 deficiencies
N-acetylglutamate Synthase
Carbamoyl phosphate synthetase I deficiency
73
Ornithine Transcarbamylase deficiency
findings
Urea cylce disorder
Body cant eliminate ammonia
Excess Carbamoyl phosphate ----\> Orotic acid (pyrimidine synthesis)
Incr. **Orotic acid**/ decr. BUN/ **hyperammonemia**
74
Ammonia transport
how is it transported from tissues to be excreted
glutamate and alanine
75
Pyruvate transport (glucose-alanine cycle)
76
Hartnup Disease
cant transport Tryptophan --\> means you get a deficiency in Serotonin and **Niacin**
lack of niacin--\> Pallagra smptoms
77
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
78
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)
79
Maple syrup urine dz
whats decreased? presentation? tx?
Decreased degredation of **branced** amino acids
**I**soleucine **L**eucine **V**aline
(I love vermont *Maple syrup Branches*1)
Decr. alpha keto acid dehydrogenase
- CNS defects, urine **smells** like **maple/burnt sugar**
- restriction of ILV from diet. Thiamine supplement
80
Alkaptonuria
finding
congenital deficiency of **homogentisate oxidase**
Cant turn **Tyrosine into Fumarate**
-**Bluish-black skin & sclera /** arthritis
**pee turns dark** after exposure to air
81
Homocystinuria
what causes it? presentaiton
Build up of homocystine
due to lack of b6 (pyridoxine) or b12(cobalamin)
marfans/vessel damage
82
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
83
Glycogen storage dz
**V**ery **p**oor **C**arb **m**etabolism
Type 1: Von Gierks dz
Type 2: Pompe dz
Type 3: Cori dz
Type 5: McArdle dz
84
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* (**g**out)
85
Pompe dz
whats special bout this one
Type 2 glycogen storage dz
Lysosomal
**P**ompe trashes the **P**ump (severe heart problems)
86
Cori dz
deficiency
glycogen storage dz Type 3
**debranching enzyme A-1,6 glucosidase**
normal lactate levels
87
McArdle dz
deficiency? what happens when they exercise?
type 5 glycogen storage dz
***_glycogen phosphorylase***_ / _***muscle phosphorylase_***
Incr. glyocen in **M**uslce becase you cant break it down w/o glycogen phosphorylase
**M**uscle cramps, **M**yoglobinuria (red urine) with excercise / 2nd wind phenomenon
88
Lysosomal storage dz's
list em
_Sphingolipidoses_
Fabry, Gaucher, Niemann-Pick, Tay-Sachs, Krabbe, Metachromatic leukodystrophy
_Mucopolysaccharidoses_
Hurler, Hunter
89
Fabry Dz
Deficient enzyme? and build up of what
lysosomal storage dz
Triad: Periph neuropathy, angiokeratomas, hypohidrosis (diminished sweating)
**A-galactosidase A** / **Ceramide trihexoside**
90
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
91
Niemann-Pick dz
deficient? build up? findings
Lysosomal storage dz
**Sphingomyelinase** / **Sphingomyelin**
neurodegeneration/ **cherry red macula / Hepatosplenamegaly**
92
Tay-sachs dz
deficient? build up? findings
lysosomal storage dz
**Hexosaminidase A / GM2 ganglioside**
**Cherry red on macula,** onion skin lysosomes, (no hepatosplenomegaly)
93
Krabbe dz
deficient? build up? findings
lysosomal storage dz
**B-galactocidase / Galactocidase + psychosin**
Optic atrophy, **destroys myelin sheath**
94
Metachromatic leukodystrophy
deficient? build up? findings
Lysosomal Storage do / demyelinating do
**Arylsulfatase A / Sulfatides**
destroys myelin, ataxia, dementia
95
Hurler Syndrome
deficiency? build up? findings?
lysosomal storage dz - **Gargoylism**
**A-L-iduronidase** / **heparan & dermatan sulfate**
Gargoylism, **corneal clouding**
96
Hunter Syndrome
deficiency? buildup? findings
lysosomal storage dz
**Iduronate sulfatase** / **heparan & dermatan sulfate**
aggresive behavior, no corneal clouding
97
what is needed in fatty acid **Synthesis**
whats the end product?
**Citrate**
from the mitochondria "SYtrate"
**palmitate**
98
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
99
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**
100
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
101
Dietary fuel
kcal of protein, carb, fat, alcohol
1g of protein/carb: 4 kcal
1g of fat: 9 kcal
1g of alcohol: 7kcal
102
what happens after a fed state?
Insuline stimulates storage of **lipids, proteins, glycogen**
via Glycogen synthase
103
what happens in a fasting state (between meals)
Hepatic glycogenolysis
via **glucagon & epinephrine** stimulation
glycogen phosphorylase
104
Cholesterol
function? rate limiting step?
used to maintain **cell membrane**,
synthesize **bile acid, steroids** and **Vit D**.
**HMG-CoA reductase** is rate limiting
