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330 Cards in this Set
- Front
- Back
cystinuria is a defect of which aa transporter?
|
positively charged aas--> cysteine, ornithine, lysine, arginine
|
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cystinuria - where is the transporter located that is defective?
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proximal convoluted tubule of kidney
|
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What are two signs of cystinuria?
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cystinuria and cysteine kidney stones
|
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What's the inheritance pattern for cystinuria?
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autosomal recessive
|
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What's the treatment for cystinuria?
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acetazolamide to alkalinize the urine
|
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In cystinuria, how would stones be described?
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yellow-brown, hexagonal morphology
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homocysteinuria- what enzyme is deficient (2)?
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homocysteine methyltransferase or cystathionine synthase
|
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What is a way you can get homocysteinuria besides having an enzyme deficiency?
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cystathionine synthase could have decreased affinity for B6
|
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Draw the pathway for how you get from methionine --> cysteine
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see FA
|
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increased homocysteine in urine, MR, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis (MI, etc). Dx?
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homocysteinuria
|
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Does purine synthesis start with base or sugar?
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sugar
|
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What is the rate-limiting enzyme of purine synthesis?
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Glu-PRPP amidotransferase
|
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Where does 6MP act?
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Inhibits PRPP synthetase (purine synthesis)
|
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Where does mycophenolic acid act?
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Blocks IMP --> GMP (enzyme is inosine monophosphate dehydrogenase), purine synthesis
|
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Describe how SCID related to adenosine deaminase deficiency works.
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Adenosine deaminase is needed to break down adenosine --> inosine which then goes to hypoxanthine.
You can't break down ATP/dATP so it feedback inhibits ribonucleotide reductase and leads to decreased DNA synthesis and lymphocyte count |
|
How does UV light damage DNA?
|
pairs thymine to thymine on same strand
|
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What does DNA helicase do?
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unwinds DNA
|
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What does DNA topoisomerase do?
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relieves supercoils
|
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What antibiotic inhibits prokaryote topoisomerase?
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fluoroquinonlones
|
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Name a fluoroquinonlone
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ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enoxacin
|
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What does prokaryotic DNA pol III do?
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elongates leading strand by adding nucleotides to 3' end and elongates lagging strand til it reaches the primer of the preceding fragment
|
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What does prokaryotic DNA pol I do?
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degrades primer and fills in gap with DNA
|
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What type of DNA repair goes wrong in xeroderma pigmentosum?
|
nucleotide excision repair
|
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What are signs/symptoms of xeroderma pigmentosum?
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dry skin with melanoma and other cancers (like basal cell carcinoma)
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Name 4 diseases that are from DNA repair defects:
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ataxia telangiectasia, bloom's syndrome, HNPCC, BRCA1/BRCA2
|
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For each type or RNA (r, m, t), say one characteristic
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r- most abundant (rampant), m- massive (longest), t- smallest (tiny)
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Which type of RNA pol makes which type of RNA?
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rRNA- pol I, mRNA- pol II, tRNA pol III
|
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What is the mRNA start codon?
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AUG
|
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What does mRNA start codon code for in eukaryotes?
|
methionine
|
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What are the 3 mRNA stop codons?
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UGA, UAA, UAG
|
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Describe where ATP and GTP are needed in translation.
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ATP- needed to charge tRNA
GTP- needed to add charged tRNA to A-site and translocation |
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Which antibiotic class inhibits the 50s peptidyl transferase (2)?
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chloramphenicol and streptogramins
|
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Which antibiotic classes bind 50s and block translocation?
|
macrolides, clindamycin, linazolid
|
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Where are ribosomes synthesized?
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in the nucleus
|
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Name 3 degradation mechanisms for proteins.
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ubiquitinylation (proteasomal)
lysosomal degradation Ca2+ dependent enzymes |
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How many ATPs per NADH?
|
3
|
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How many ATPs per FADH2?
|
2
|
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How many ATPs per glucose?
|
24 from TCA cycle + 12 (or 14) from glycolysis
|
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Where does TCA cycle occur?
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mitochondria
|
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Name the TCA intermediates in order
|
citrate --> isocitrate --> alpha-ketoglutarate --> succinyl coA --> succinate --> fumarate --> malate --> OAA
(can remember Citrate Is Krebs' Starting Substrate For Making OAA) |
|
What are the cofactors required for alpha-ketoglutarate dehydrogenase?
|
thiamine (B1), lipoic acid, CoA (B5), FAD (B2), NADH (B3)
|
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Which proteins can you not synthesize in abetalipoproteinemia?
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Apo B 100 (VLDL secretion), Apo B48 (chylomicron secretion)
|
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Where do lipids accumulate in abetalipoproteinemia?
|
In enterocytes
|
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What are the physical findings in abetalipoproteinemia?
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failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness
|
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Treatment for abetalipoproteinemia?
|
Vitamin E
|
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Familial hypercholesterolemia:
Cholesterol levels in homozygotes and heterozygotes? |
Homo-700+ mg/dL, hetero- ~300 mg/dL
|
|
Familial hypercholesterolemia:
Complications? |
atherosclerotic disease, tendon xanthomas, MI
|
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Familial hypercholesterolemia:
Where do xanthomas tend to form? |
achilles
|
|
Familial hypercholesterolemia:
Inheritence pattern? |
autosomal dominant
|
|
Hyperchylomicronemia:
What is elevated? |
TG (very) and cholesterol (less so)
|
|
Hyperchylomicronemia:
What are the sequelae? |
pancreatitis, hepatosplenomegaly, xanthomas
NOT athero |
|
What is elevated in hypertriglyceridemia?
|
TGs only
|
|
What are the sequelae of hypertriglyceridemia?
|
pancreatitis
|
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What 3 aas are needed for purine synthesis?
|
glycine, aspartate, glutamine
|
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What are the sources of carbon for purine molecules?
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CO2, TH4 (FOLATE), glycine
|
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What substances are needed to make pyrimidines?
|
glutamine + CO2 --> carbamoyl phosphate
+ aspartate, glutamine, TH4 |
|
What substances provide the carbons in pyrimidine?
|
aspartate, CO2
|
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Do you start with sugar or base for purine synthesis?
|
Sugar (think PURE SUGAR)
|
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Do you start with sugar or base for pyrimdine synthesis?
|
base
|
|
What's the rate-limiting enzyme for pyrimidine synthesis?
|
carbamoyl phosphate synthase II
|
|
Where does hydroxyurea act?
|
blocks ribonucleotide reductase (pyrimidine synthesis)
|
|
Where does 5 FU act?
|
blocks thymidylate synthase; pyrimidine synthesis
|
|
Where does methotrexate act?
|
blocks dihidrofolate reductase which is needed to go from DHF to THF , which is then turned into N5,N10 methylene THF and needed for pyrimidine synthesis
|
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What is the equivalent of methotrexate for bacteria?
|
trimethoprim
|
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less condensed chromatin is called?
|
euchromatin
|
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Name the purines
|
Guanine, adenine
|
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Pyrimidines are (names)
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cytosine, thymidine, uracil
|
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chemical group on guanine?
|
ketone
|
|
what reaction changes cytosine --> uracil?
|
deamination
|
|
What's the chemical group on thymine?
|
methyl
|
|
G forms hydrogen bonds with which base?
How many? |
C
3 |
|
A forms H bonds with which base?
How many? |
T
2 |
|
Base + ribose is called?
|
nucleoside
|
|
Base + ribose + phosphate is called?
|
nucleotide
|
|
Duchenne's/Becker's muscular dystrophy:
Inheritence? |
x-linked recessive
|
|
What gene is affected in Duchenne/Becker's?
|
dystrophin
|
|
Duchenne/Beckers:
What is the molecular different between the two? |
In Duchenne, dystrophin gene is deleted; in Becker's, it's mutated (more mild phenotype)
|
|
What does dystrophin do?
|
helps anchor muscle fibers, especially in skeletal and cardiac muscle
|
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How do you diagnose Duchenne/Beckers?
|
Increased CPK + muscle biopsy
|
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What are the physical findings in Duchenne/Beckers?
|
pseudohypertrophy of calf muscles, Gowers maneuver (using upper extremities to help stand up)
|
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Neurofibromatosis Type 1: physical findings
|
neurofibroma (brain), schwannoma, optic nerve glioma, hamartoma of the iris (aka Lish nodule), cafe au lait spots, and skeletal (scoliosis/kyphosis)
|
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NF1 is also called?
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von Recklinghausen's disease
|
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NF type 1 is found on what chromosome?
|
Chromosome 17
|
|
NF 2- gene and chromosome
|
NF2 gene on chromosome 22
|
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NF2 findings (two)
|
bilateral acoustic schwannomas, juvenile cataracts
|
|
Tuberous Sclerosis:
Findings? |
Cortical tubers (hamartomas), seizures, MR, astrocytomas, retinal hamartomas, ash leaf spots, angiofibromas (adenoma sebaceum on face), rhabdomyoma, renal angiomyolipomas
|
|
Tuberous Sclerosis:
What genetic concept is demonstrated? |
Incomplete penetrance, variable presentation
|
|
Von Hippel Lindau:
Associated tumors |
hemangioblastomas of retina/cerebellum/medulla, multiple bilateral renal cell carcinomas, pheochromocytomas
|
|
Von Hippel Lindau:
What does the gene deletion lead to? |
constituitive expression of HIF transcription factor --> activation of angiogenic growth factors
|
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What two drugs are metabolized by XO?
|
6MP/azathioprine
|
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What happens when you give azathioprine/6MP + allopurinol?
|
The first drug is too strong bc XO is blocked and can't metabolize it
|
|
Enzyme HGPRT catalyzes what reaction?
|
Guanine or hypoxanthine (base w/ no sugar or phosphate) --> GMP or IMP (nucleotide +sugar, + phosphate)
|
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What are the findings in Lesch Nyhan syndrome?
|
hyperuricemia, gout, aggression, self-mutilation, choreoathetosis (involuntary movements)
|
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What is the inheritance pattern of Lesch Nyhan syndrome?
|
x-linked recessive
|
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Familial Adenomatous Polyposis:
Chromosome & gene that's mutated |
APC gene on chromosome 5
|
|
Familial Adenomatous Polyposis:
Name two other diseases (besides FAP) that have APC gene mutations |
Turncott's and Gardiner's syndrome
|
|
Autosomal Dominant Polycystic kidney disease:
What do kidneys look like? |
bilateral, massive enlargement, multiple large cysts
|
|
Autosomal Dominant Polycystic kidney disease:
How does disease present? |
flank pain, hematuria, hypertension, renal failure
|
|
Autosomal Dominant Polycystic kidney disease:
90% of cases due to mutation in ? |
ADPKD1 gene
|
|
Autosomal Dominant Polycystic kidney disease:
Other pathology associated with ADPKD (3)? |
polycystic liver disease, berry aneurysms, and mitral valve prolapse
|
|
Achondroplasia:
Due to defect in ? |
FGF receptor 3
|
|
Achondroplasia:
Inheritance? |
autosomal dominant
|
|
Hereditary Hemorrhagic Telangiectasia:
What is it also called? |
Oscar-weber-rendu syndrome
|
|
Hereditary Hemorrhagic Telangiectasia:
Name 4 findings |
telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations
|
|
Hereditary Hemorrhagic Telangiectasia:
Inheritance? |
Autosomal dominant
|
|
Hereditary Spherocytosis:
What is the genetic defect? |
Problem with spectrin/ankyrin
|
|
Hereditary Spherocytosis:
Presentation |
spherocytes, hemolytic anemia, increased MCHC
|
|
Hereditary Spherocytosis:
Treatment? |
splenectomy
|
|
Hereditary Spherocytosis:
diagnosis? |
osmotic fragility test
|
|
Hereditary Spherocytosis:
inheritance? |
autosomal dominant
|
|
Edwards Syndrome:
What would you see on quad screen? |
decreased betaHCG, dec. AFP, dec. estriol
|
|
Edwards Syndrome:
Findings |
severe MR, rocker-bottom feet, micrognathia, low-set ears, clenched hands, prominent occiput
|
|
Patau Syndrome:
Findings |
severe MR, rocker-bottom feet, microcephatly, microophthalmia, cleft lip/palate, holoprosencephaly, polydactyly
|
|
What findings are unique to Edwards syndrome?
|
micrognathia, clenched hands
|
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What sx are unique to Patau syndrome?
|
cleft lip, holoprosencephaly, polydactyly
|
|
22q11 deletion syndromes (general):
Findings |
cleft palate, abnormal facies, thymic aplasia, cardiac defects, HYPOCALCEMIA
|
|
Findings specifically in diGeorge syndrome?
|
thymic, parathyroid, and cardiac defects
|
|
Findings specifically in velocardiofacial syndrome?
|
palate, facial, cardiac
|
|
22q11 deletion syndromes:
Due to aberrant development of? |
3rd and 4th branchial pouches
|
|
NAD associated with which vitamin?
|
Niacin (B3)
|
|
FAD associated with which vitamin?
|
Riboflavin (B2)
|
|
Describe enzyme & sx:
Essential fructosuria |
Enzyme- fructokinase
Sx- asymptomatic but fructose appears in blood and urine |
|
Describe enzyme & sx:
Fructose intolerance |
Enzyme- aldolase B
Sx- end up with inc. fructose 1-P and less free phosphate --> hypoglycemia, jaundice, cirrhosis, vomiting |
|
Treatment for fructose intolerance?
|
decrease intake of fructose & sucrose (glucose + fructose)
|
|
What drug inhibits alcohol --> acetaldehyde?
|
fomepizole
|
|
What drug inhibits acetaldehyde --> acetate?
|
disulfiram
|
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An end product of alcohol metabolism is acetyl co-A. Name two things acetyl-co A can be made into.
|
1) ketone bodies
2) fatty acids |
|
Describe how alcohol inhibits gluconeogenesis.
|
Because NADH is a cofactor to change OAA to malate, which stops OAA --> PEP --> glucose via gluconeogenesis
|
|
Pyruvate dehydrogenase deficiency would lead to what symptoms?
|
lactic acidosis, neurologic defects
|
|
What is the treatment for pyruvate dehydrogenase deficiency?
|
increase ketogenic foods bc that will bypass pyruvate dehydrogenase and enter the TCA cycle later
|
|
Give examples of ketogenic nutrients (what do they contain?)
|
high in fat, lysine, leusine
|
|
How many pyruvates / glucose metabolized?
|
2
|
|
Two things that activate PFK-1
|
AMP, fructose 2,6, BP
|
|
Two things that inhibit PFK-1
|
ATP, citrate
|
|
PEP --> pyruvate (enzyme?)
|
pyruvate kinase
|
|
What increases action of pyruvate kinase?
|
fructose 1,6 BP
|
|
What decreases action of pyruvate kinase (2 things)?
|
ATP, alanine
|
|
Draw out how PRK 1 regulation works
|
See FA p. 98
|
|
Which enzyme to convert glucose to G6P is only in liver/ beta cells of pancreas?
|
glucokinase
|
|
Which enzyme to convert glucose to G6P is ubiquitous?
|
hexokinase
|
|
Which enzyme that converts glucose to G6P has high affinity?
|
hexokinase
|
|
Which enzyme that converts glucose to G6P is induced by insulin?
|
glucokinase (bc you want liver to make glycogen w. the glucose)
|
|
Which enzyme that converts glucose to G6P has a high vmax?
|
glucokinase (is a GLUTTON)
|
|
What's the most common human enzyme deficiency?
|
G6PD deficiency
|
|
Two associated RBC pathologies with G6PD deficiency?
|
bite cells, heinz bodies
|
|
Name the drugs that cause oxidative damage.
|
FIND SPAIN
F- fava beans, I- isoniazid, N-naphthalin, D-dapsone, S-sulfonamide, P-primaquine, A-aspirin, I-ibuprofinm, N-nitrofurantoin |
|
Name an enzyme deficiency aside from G6PD that causes RBC lysis.
|
pyrvuate kinase deficiency
|
|
What's the rate limiting enzyme of gluconeogenesis?
|
fructose 1,6, bisphosphatase
|
|
In gluconeogenesis, from pyruvate, where do you do and what's the cofactor?
|
pyruvate --> OAA, pyruvate carboxylase, cofactor is biotin
|
|
Fructose 1, 6, BP --> fructose 6 P is catalyzed by?
|
fructose 1, 6 bisphosphatase
|
|
Fructose 1, 6, bisphosphatase is the opposite of which enzyme in glycolysis?
|
PFK-1
|
|
What enzyme catalyzes G6P --> glucose?
|
glucose 6 phosphatase
|
|
Why do only odd-chain fatty acids net glucose when they enter the TCA cycle?
|
Because acetyl-coA is a breakdown product of even chain fatty acids, and when acetyl coA enters TCA cycle, first step is to add OAA, which leads to lost CO2 and thus you don't actually keep the carbon you are putting into the cycle
|
|
Name three causes of cherry-red spot on macula
|
- Tay Sachs, Niemann Pick, and central retinal artery occlusion
|
|
5% of Down syndrome cases are due to two genetic phenomenae... what are they?
|
1) robertsonian translocation (4%)
2) down mosaicism (1%) |
|
What chromosome is affected in cri du chat?
|
5
|
|
What chromosome is affected in Williams syndrome?
|
7
|
|
Findings in Williams syndrome?
|
well-developed verbal skills, MR, hypercalcemia, elfin facies, extreme friendliness w/ strangers, heart problems
|
|
Glycogen Synthesis-
1) Rate limiting enzyme 2) What type of linkage is the linear? 3) What kind of linkage is the branch? |
1) glycogen synthase
2) alpha 1,4 3) alpha 1,6 |
|
Describe the impact (molecular) and the name of the associated disease:
1) glucose 6 phosphatase 2) Lysosomal alpha 1,4 glucosidase 3) Debranching enzyme 4) skeletal muscle glycogen phosphorylase |
1) can't turn glycogen back into glucose and can't complete glycolysis- Von Gierke
2) can't break down glycogen in lysosomes; Pompe's disease 3) Can't break branches down (once there are four glucoses left), Cori's disease 4) can't break down glycogen in muscle; McArdle's disease |
|
Glycogenolysis:
1) Rate-limiting enzyme |
1) glycogen phosphorylase
|
|
Name the glycogen storage disease with these findings:
1) muscle cramps, myoglobinurea with exercise 2) cardiomegaly, systemic findings 3) mild, normal blood lactate levels 4) severe hypoglycemia (fasting), highly increased liver glycogen, increased blood lactate, hepatomegaly |
1) McArdles
2) Pompe's 3) Cori's 4) Von Gierke's |
|
What do you get lactic acidosis in Von Gierke's disease?
|
Because you can't complete gluconeogenesis so you do more glycolysis and some of that goes to lactate
|
|
In which glycogen storage disease do you normally see death by age 3?
|
Pompe's disease
|
|
Ocular albinism genetics?
|
x-linked recessive
|
|
Wiskott-Aldrich syndrome genetics?
|
x-linked recessive
|
|
HMP Shunt:
1) Rate limiting enzyme 2) Name two important HMP intermediates |
1) G6PD
2) NADPH, ribulose 5 phosphate (used in purine synth) |
|
Name at least 4 processes where NADPH is used
|
steroid/fatty acid synthesis, respiratory burst, glutathione reductase, p-450
|
|
How many ATPs are used in HMP shunt?
|
0
|
|
How is NADPH used to generate respiratory burst?
|
It's a cofactor for NADPH oxidase to turn O2 into oxygen free radical
|
|
Describe the changes (enzymes and intermediates) to go from O2 --> HOCl.
|
See FA p. 102
|
|
How is NADPH used to help protect cells from oxidative damage?
|
NADPH reduces glutathione and reduced glutathione accepts oxygen from H2O2 to form H2O
|
|
What is the job of apoprotein A-1?
|
activates LCAT
|
|
What is the job of apoprotein B100?
|
binds LDL receptor, mediates VLDL secretion (from liver)
|
|
What is the job of apoprotein C-II?
|
cofactor for lipoprotein lipase
|
|
What is the job of Apo B-48?
|
mediates chylomicron secretion
|
|
What is the job of apoprotein E?
|
mediates extra remnant uptake
|
|
What are the symptoms of ammonia intoxication?
|
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurred vision
|
|
What is the treatment for ammonia toxicity (due to urea cycle disorders)
|
benzoate or phenylbutyrate + less protein in diet
|
|
Tx for ammonia toxicity due to liver failure?
|
lactulose
|
|
What is mechanism of action of lactulose to treat ammonia toxicity secondary to liver failure?
|
creates acidic environment in colon and draws NH4+ to it (osmotic diarrhea)
|
|
What receptor does liver use to take up chylomicron remnants?
|
LRP - LDL receptor protein
|
|
What two forms of lipoproteins are released from the liver?
|
VLDL, HDL
|
|
What enzyme transfers cholesterol from cells to nascent HDL?
|
LCAT
|
|
What enzyme does HDL use to deposit cholesterol onto LDL (which then goes back to liver)?
|
CETP (cholesterol ester transfer protein)
|
|
How does HDL deposit cholesterol directly onto liver?
|
SRB1
|
|
What happens to cholesterol in liver?
|
turned into bile acids, which can be excreted or reabsorbed
|
|
Where does fatty acid synthesis occur?
|
cytosol
|
|
What is the rate limiting enzyme in fatty acid synthesis?
|
acetyl coA carboxylase
|
|
What is the rate-limiting enzyme of fatty acid breakdown?
|
carnitine acyltransferase 1
|
|
sx of carnintine deficiency?
|
weakness, hypotonia, hypoketotic hypoglycemia
|
|
Where does fatty acid degradation occur?
|
mitochondria
|
|
What enzyme esterifies 2/3 of body cholesterol?
|
LCAT (lecithin-cholesterol acyl transferase)
|
|
What is the first enzyme in the urea cycle? Where is it located?
|
carbamoyl phosphate synthetase 1, in mitochondria
|
|
What enzyme catalyzes carbamoyl phosphate --> citrulline + ornithine
|
ornithine transcarbamoylase
|
|
Name three findings in OTC deficiency
|
decreased BUN (no urea in blood), hyperammonemia, increased orotic acid in blood and urine
|
|
What must a transcription factor do?
|
bind to promotor region
|
|
What are other names for the promotor region?
|
-25 Hogness/pribnow/TATA box/-75 CAAT
|
|
Name 4 structural motifs TFs can have to bind DNA
|
helix loop helix, helix turn helix, zinc finger, leucine zipper
|
|
What is the difference between a repressor/inducer in the operator region and an enhancer or repressor region?
|
the former controls whether or not transcription occurs, the latter controls the rate of transcription when bound by protein factors
|
|
What chemical inhibits eukaryotic RNA pol II?
|
alpha amanitin, found in death cap mushrooms
|
|
What antibiotic inhibits prokaryotic RNA polymerase?
|
rifampin
|
|
Where is rRNA synthesized?
|
nucleolus
|
|
Where is tRNA/mRNA synthesized?
|
nucleoplasm
|
|
Name two ways of prokaryotic transcription termination
|
- GC rich region followed by uracil rich region
- Rho factor of e. coli- ATPase just clips off polymerase |
|
Maple Syrup Urine Disease
1) What is the malfunction (inc. enzyme) 2) Which aas are affected? 3) What are the physical findings? |
1) can't break down branched chain aas (lack of alpha keto acid dehydrogenase)
2) leucine, isoleucine, valine 3) Urine smells like maple syrup, CNS defects, MR, death |
|
Hartnup's Disease
1) Genetics? 2) What's defective? 3) Where is it? 4) Findings? |
1) autosomal recessive
2) neutral aa transporter 3) renal and intestinal epithelial cells 4) pellagra (bc tryptophan needed to make niacin), tryptophan excretion from urine |
|
For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Fabry's |
1) Enzyme: alpha galactosidase
2) Substrate: ceramide trihexoside 3) Genetics: x-linked recessive 4) Findings: peripheral neuropathy of hands/feet, angiokeratomas, cardio/renal disease |
|
For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Gaucher's |
1) Enzyme: beta-glucocerebrosidase
2) Substrate: glucocerebroside 3) Genetics: autosomal recessive 4) Findings: hepatosplenomegaly, aseptic necrosis of femur, bone crises, crumpled tissue paper macrophages |
|
For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Niemann Pick Disease |
1) Enzyme: sphingomyelinase
2) Substrate: sphingomyelin 3) Genetics: autosomal recessive 4) progressive neurodegeneration, hepatosplenomegaly, cherry red macula, foam cells, severe MR |
|
For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Tay-Sachs Disease |
1) Enzyme: hexosaminidase A
2) Substrate: GM2 ganglioside 3) Genetics: autosomal recessive 4) Findings: progressive neurodegeneration, seizures, developmental delay, cherry red macula, lysosomes w/ onion skinning |
|
For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Krabbe's Disease |
1) Enzyme: Galactocerebrosidase
2) Substrate: galactocerebroside 3) Genetics: autosomal recessive 4) Findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells |
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For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Metachromatic Leukodystrophy |
1) Enzyme: Arylsulfatase A
2) Substrate: Cerebroside Sulfate 3) Genetics: autosomal recessive 4) Findings: central and peripheral demyelination with ataxia, dementia |
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For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Hurler's |
1) Enzyme: alpha-L-iduronidase
2) Substrate: heparan sulfate, dermatan sulfate 3) Genetics: autosomal recessive 4) Findings: developmental delay, gargoylism, airway obstruction, corneal clouding |
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For each disease, name the deficient enzyme, accumulated substance, genetics, and main findings:
Hunter's |
1) Enzyme: iduronadate sulfatase
2) substrate- dermatam sulfate, heparan sulfate 3) Genetics: x-linked recessive 4) Mild Hurler's + aggressive behavior, NO corneal clouding |
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I Cell Disease
1) Description 2) Molecular consequences 3) Findings |
1) Failure of addition of mannose 6 phosphate to lysosome proteins
2) enzymes secreted outside the cell instead of targeted to lysosomes 3) Findings: coarse facial feature, restricted joint movement, high plasma levels of lysosomal enzymes +/- MR |
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Which lysosomal storage disease is associated with renal failure?
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Fabry's disease
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Which two lysosomal storage diseases are x-linked recessive?
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Fabry's and Hunter's
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Most common lysosomal storage disease?
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Gaucher's
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Which lysosomal storage diseases are associated with early death?
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Tay Sachs, Niemann Pick, Krabbe's
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Which lysosomal storage disease is a demyelinating disease?
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Metachromatic Leukodystrophy
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Which disease are these deficiencies associated with?
1) alpha-L-iduronidase 2) Iduronadate sulfatase 3) Failure of addition of mannose 6 phosphate to lysosome proteins |
1) Hurler's disease
2) Hunter's 3) I-cell disease |
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Name the disease assoc. with these enzyme deficiencies:
1) alpha galactosidase A 2) beta glucocerebrosidase 3) sphingomyelinase 4) hexosaminidase A |
1) Fabry's
2) Gaucher's 3) Niemann Pick 4) Tay Sachs |
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Name the disease assoc. with these enzyme deficiencies:
1) galactocerebrosidase 2) arylsulfatase A |
1) Krabbe's disease
2) metachromatic leukodystrophy |
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3 complications of marfan syndrome
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1) aortic incompetence --> dissecting aortic aneurysms
2) floppy mitral valve 3) subluxation of lenses also berry aneurysms |
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Genetics of marfan syndrome
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autosomal dominant
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Albinism could be a deficiency of what two things?
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tyrosinase (enzyme that catalyzes tyrosine --> melanin) or defective tyrosine transporters
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What is a non-enzymatic cause of albinism?
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failure of neural crest cells to migrate
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What type of inheritence is tyrosinase deficiency?
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autosomal recessive
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Describe how transaminases are made
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based on donor of amino group (ie alanine aminotransferase)
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What cofactor is required for aminotransferases? what is it derived from?
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cofactor- pyridoxal phosphate
derived from- vitamin B6 |
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What are the cofactors needed by the pyruvate dehydrogenase complex?
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thiamine (B1), lipoic acid, coA (B5), FAD (B2), NAD (B3)
"Tender Loving Care for No One" |
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What rxn does pydruvate dehydrogenase complex catalyze?
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pyruvate --> acetyl coA
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Where does glucose 6P --> glucose?
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in the ER
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What does the CFTR transporter do?
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actively secretes Cl- in lungs and GI tract and actively reabsorbs Cl- from sweat
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What is the most common mutation in CF?
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Deletion of Phe 508
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CF complications?
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recurrent pulmonary infections, bronchiti, bronchiectasis, pancreatic insufficiency, meconium ileus
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Why are males who have CF infertile?
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bilateral absence of vas deferens
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Name two bacteria that cause infection in CF
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pseudomonas & S. aureus
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Name another disease associated with meconium ileus
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Hirschsrpung's disease
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signs/sx of prader willi
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hypotonia, poor feeding, almond shaped eyes, down-turned mouth. later: hyperphagia, obesity, short stature, MR, behavior disorders (skin picking), hypogonadotropic hypogonadism
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Signs/sx of Angelman syndrome
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"happy puppet" syndrome, ataxia, inappropriate laughter
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Name sample & probe for southern, northern, western blots:
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Southern- sample DNA, probe DNA
Northern- sample RNA, probe DNA Western- sample protein, probe Ab |
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Describe how FISH works
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fluorescent DNA or RNA probe binds to gene of interest --> fluorescence indicates gene of interest is present
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What phase of mitosis are chromosomes in for karyotype?
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metaphase
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What type of antiobiotic binds 30s subunit, preventing tRNA attachment?
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tetracycline
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What type of antiobiotic inhibits formation of the inititation complex and causes misreading of mRNA?
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aminoglycosides
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Which site does first Met get put in in ribosome?
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P site
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Where do other incoming tRNAs get put?
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A site
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What does ribozyme (aka peptidyl transferase) do?
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transfers growing polypeptide (P site) to new aa (A site)
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Findings in Down Syndrome?
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MR, flat facies, prominent epicanthal folds, simian crease, gap bt 1st and 2nd toes, duodenal atresia, congenital heart disease (endocardial cushion defects)
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What 3 things are DS patients at risk for later in life? (other than heart problems)
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ALL, AML, Alzheimer's disease
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What would you see on quad screen with Down Syndrome?
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decreased AFP, increased beta hCG, decreased estriol, increased inhibin A
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What would DS ultrasound show?
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nuchal translucency (could also see with Turner's)
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What would you use for definitive DS diagnosis?
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FISH
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95% of cases of DS are due to?
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meiotic nondisjunction
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Describe what's being made and being used:
post absorptive period (4-6 hours) |
made- glucose (via glycogenolysis and a little bit of gluconeogenesis), adipose is releasing FFAs
Mostly glucose is being used |
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Describe what's being made and being used:
early starvation (24 hours) |
Made- glucose via glycogenolysis (less) and gluconeogenesis (more), FFAs
Brain/RBCs use glucose, muscle & liver use FFAs |
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Describe what's being made & being used: intermediate starvation (2-3 days)
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glucose made via gluconeogenesis, FFAs, ketone bodies
Brain uses glucose and ketone bodies, muscle/liver use FFAs, ketone bodies (can't be used by liver) |
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Which organ can't use ketone bodies?
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liver
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Name 3 diseases where you would see high ketone bodies?
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1) diabetic ketoacidosis
2) alcoholism 3) prolonged starvation |
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What is the rate limiting enzyme for ketogenesis?
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Hmg CoA synthase
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Name the essential aas
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Phe, Val, Trp, Thr, Ile, Met, His, Arg, Leu, Lys
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Name three basic aas
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Arg, Lys, His
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When do you need to supplement ketogenic aas?
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in pyruvate dehydrogenase deficiency
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Draw the pathway of phenylalanine to Epi
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See FA p. 106
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What's the treatment for classic galactosemia?
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avoid galactose and lactose
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Huntington's disease:
1) Chromosome 2) Trinucleotide repeat? 3) Findings? 4) Neurotransmitters that are unusual |
1) 4
2) CAG 3) Depression, dementia, choreiform movements, caudate atrophy 4) Decreased GABA, decreased AcH |
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Myotonic dystrophy, trinucleotide repeat?
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CTG
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What is the inheritence of phenylketonuria?
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autosomal recessive
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What is the inheritence of hemochromatosis?
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autosomal recessive
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What is the inheritence of thalassemias?
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autosomal recessive
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What is the inheritence of sickle cell anemias?
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autosomal recessive
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Findings in fragile x?
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macro-orchidism (enlarged testes), long face with large jaw, large everted ears, autism, mitral valve prolapse
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Trinucleotide repeat in fragile x?
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CGG
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Electron Transport:
What happens at complex I? |
NADH --> NAD+
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Electron Transport:
What happens at complex II? |
FADH --> FAD+
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Protons are being transferred from where to where in electron transport chain?
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mitochondrial matrix --> intermembranous space, across inner mitochondrial membrane
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Drugs that inhibit complex I?
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amobarbital, rotenone, amytal, MPP (from meperidine, street drug)
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Drugs that inhibit complex III?
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Antimycin A
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Drugs that inhibit complex IV?
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H2S, CO, CN-, N3
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Name three uncoupling agents
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2,4 DNP (wood preservation agent), aspirin, thermogenin in brown fat
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What's the difference between kinase and phosphorylase?
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kinase- uses ATP to add PO4
phosphorylase- no ATP to add PO4 |
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What does phosphatase do?
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removes phosphate
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What does dehydrogenase do?
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oxidizes substrate
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What does carboxylase do?
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adds one carbon
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What is the normal cofactor for carboxylase?
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biotin
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Name the chemical moiety carried by the carrier:
ATP |
phosphoryl groups
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Name the chemical moiety carried by the carrier:
NADH/FADH2 |
electrons
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Name the chemical moiety carried by the carrier:
coenzyme A/lipoamide |
acyl groups
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Name the chemical moiety carried by the carrier:
biotin |
CO2
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Name the chemical moiety carried by the carrier:
TH4 |
1-carbon units
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Name the chemical moiety carried by the carrier:
SAM |
methyl groups
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Name the chemical moiety carried by the carrier:
TPP |
aldehyde
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Describe how methionine --> homocysteine (and back)
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see FA insert page that I added (near p. 68
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Name enzyme and sx:
Galactokinase deficiency |
enzyme- galactokinase
sx- milder, galactose in blood/urine, infantile cataracts, developmental delay |
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Name the enzyme and sx:
Classic galactosemia |
enzyme: galactose-1-phoasphate uridyl transferase
Findings: galactitol accumulates in lens of eye --> cataracts, failure to thrive, MR, jaundice, hepatomegaly |
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How is classic galactosemia different from Hurler's/Hunter's disease (regarding eyes)?
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galactosemia- cataracts, Hurler's- corneal clouding & gargoylism, Hunter's- no eye pathology
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Name the enzyme:
Tyr --> DOPA |
Tyrosine hydroxylase
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DOPA --> dopamine
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dopa decarboxylase
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What drug inhibits DOPA decarboxylase?
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carbidopa
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What enzymes break down dopamine and NE?
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MAO and COMT
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What is the dopamine breakdown product?
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homovanillic acid (HMA)
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What is the NE breakdown product?
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vanillymanelic acid (VMA)
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What two things can go wrong that --> PKU
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missing phenylalanine hydroxylase
missing BH4 cofactor |
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What aa "becomes" essential in PKU?
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tyrosine
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Name three phenylketones & what are they?
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They are the product of having excess Phe-
Phenylacetate, phenyllactate, and phenylpyruvate |
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Findings in PKU?
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musty body odor, increased phenylketones, fair skin (no melanin), eczema, MR, seizures, growth retardation
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Findings in babies with untreated PKU moms?
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microcephaly, MR, growth retardation, heart defects
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Alkaptonuria:
What is deficienct? |
homogentisic acid oxidase
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Alkaptonuria:
What does the deficient enzyme normally do? |
tyrosine --> fumarate
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Findings in alkaptonuria?
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dark connective tissue, pigmented sclera, urine turns black on standing, can get arthralgias
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Name three post-translational modifications of mRNA before it leaves the nucleus
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5' cap, poly A tail, splicing out of introns
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Where on the tRNA molecules does the aminoacyl tRNA synthetase add an AA?
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the 3' hydroxyl
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Which antibiotics bind the 30S subunit, preventing aminoacyl tRNA attachment?
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tetracyclines
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CF treatment?
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N-acetylcysteine (cleaves disulfide bonds and loosens mucus plugs), antibiotics, pancreatic enzymes, fat soluble vitamins
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MEN 1 - common malignancies
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parathyroid (PTH), pancreatic, pituitary
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MEN 2A- common malignancies
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medullary thyroid, pheochromocytoma, parathyroid
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MEN 2B- common malignancies
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medullary thyroid, pheochromocytoma, oral/intestinal ganglioneuromatosis (assoc. with marfanoid habitus)
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Two of the MEN syndromes are associated with a mutation; which ones, and what mutation?
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MEN2A/2B, ret mutation
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Inheritence of MEN syndromes?
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autosomal dominant
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Friedrich's ataxia- associated trinucleotide repeat?
|
GAA
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Fragile X syndrome:
1) Genetics 2) Gene involved? 3) What does # 2 do? 4) Name the two most common causes of genetic MR. |
1) x-linked recessive
2) FMR1 (fragile mental retardation) 3) codes for FMR protein--> found in brain and testes, involved in axon/dendrite mRNA translation 4) Down Syndrome & fragile x |
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Tryptophan --> (2 things)
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1) Niacin, 2) Serotonin
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histadine -->
Cofactor? |
histamine , B6
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Glycine --> ? --> ?
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porphyrin, heme
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Arginine --> (3)
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1) creatine
2) urea 3) Nitric oxide |
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glutamate --> (2)
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1) GABA
2) Glutathione |
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Cofactor for glutamate --> GABA?
|
B6
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Name the enzyme:
Phe --> Tyr |
Phe hydroxylase
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