-
What enzyme catalyzes the formation of cAMP?
Adenylate cyclase
-
cAMP pathway uses what type of receptor?
G protein--7 transmembrane domains
-
When a hormone binds a G protein, GDP is exchanged for what?
GTP
-
What are the 3 subunits of G protein?
-
Upon binding of a hormone, what subunit dissociates and binds the enzyme?
alpha
-
GTPase activity is present on what subunit?
alpha S
-
cAMP activates what kinase?
protein kinase A
-
Phosphorylation is usually on what a.a residue?
-
O glycosidic bonds are formed from what a.a?
-
What effect does Cholera have on the G protein activity?
activation of alpha s subunit which constitutively activates protein kinase A
-
Cholera uses what receptor?
GM1--ganglioside
-
ADP ribosylation of alpha s subunit of Gprotein is caused by what toxin?
Cholera
-
What causes constitutive activatio of alpha s Subunit of G protein?
Cholera
-
What inhibits GTPase activity of alpha s subunit?
Cholera
-
What is the sourse of ADP ribosylation?
NAD
-
What hormones act thru Gi receptor?
- ach
- angiotensin II
- somatostatin
-
What is the difference between Gs and Gi receptor proteins?
- upon activation of Gs--cAMP is activated
- Upon activation of Gi--cAMP is deactivated
-
What hormone stimulates phosphodiestarase?
Insulin
-
Methyl Xanthine has what effect on phosphodiesterase?
it inhibits it----possible hyperglycemia
-
What are the two types of Guanylyl cyclase?
-
What are the hormones that act thru cGMP?
-
ANF acts thru what type of cGMP receptor, membrane or cytosolic?
membrane
-
NO acts thru what type of cGMP receptor, membrane or cytosolic?
cytosolic (soluble)
-
cGMP stimulates what protein kinase?
protein kinase G
-
What is the action of Silenafil?
- inhibits phophodiesterase
- prevents breakdown of
-
Insulin is needed for entry of glucose into what cells?
What receptor?
- adipocytes
- skeletal muscle
- GLUT-4
-
Mutation of RAS gene causes what?
- decreased hydrolysis of GTP to GDP
- G protein is constitutively active
-
Source of ADP ribosylation?
NAD
-
What two toxins do ADP ribosylation?
-
Cholera and E.coli cause what by constitutively activating alpha s subunit?
diarhea bc of increased Cl secretion which takes water out
-
What effect does Pertussis toxin have?
whooping cough
-
Mode of action of pertussis toxin?
ADP ribosylation of Gi receptor protein
-
Insulin is made up of how many a.a?
51
-
Insulin has what kind of chains?
- intra chain disulfide bonds
- inter chain disulfide bonds
-
Initially insulin is synthesized as what?
Proinsulin
-
Where is the one polypeptide proinsulin is cut into two peptides?
Golgi Apparatus
-
Glucagon is made up of how many a.a?
29
-
Glucagon acts on what organ?
Liver
-
Glucagon stimulates glycogen metabolism in what organ?
Liver
-
What happens to acetone that is produced?
it is exhaled
-
What are the 2 organs that undergo gluconeogenesis?
-
How does the kidney compensate for the ketoacidosis?
it uses ammonia to neutralize H+
-
What kind of obesity has worse health consequence
Android
-
What is the mode of action of Orlistat?
Inhibits pancreatic lipases and gastric lipases
-
How does sibutramine work?
Serotonin or norepinephrine reuptake inhibitor
-
"Metabolic Syndrome" is associated with what?
insulin resistance
-
Why do men loose fat more easily because?
Has access to portal circulation
-
Lipoprotein lipase digests TAG found where?
-
Class III obesity is what BMI?
over 40
-
Class II obesity is what BMI?
35-40
-
Class I obesity is what BMI?
over 30
-
Numbering of purine rings is done in what direction?
Counterclockwise direction
-
Numbering of carbon and nitrogen atoms in a pyrimidine is in what direction?
clockwise
-
What is the difference between ribose and deoxyribose?
- ribose--OH on 2'
- deoxyribose--H on 2'
-
Methylation of uracil produces what?
thymine
-
What is the rate determining step of De novo purine synthesis?
Glutamine PRPP amidotransferase
-
Sulfonamides like Trimethropin inhibits what enzyme?
formyltransferase
-
Methotrexate inhibits what enzyme?
dihydrofolate reductase
-
What is the only enzyme that uses thiamine only?
trans ketolase
-
6-Mercaptopurine is an inhibitor of what 2 enzymes?
- adenylosuccinase
- IMP dehydrogenase
-
6-Mercaptopurine blocks synthesis of what 2 nucleotides?
-
Why is GTP used in the synthesis of AMP and ATP used in the synthesis of GMP?
To balance the use of nucleotides
-
Lesch-Nyhan syndrome is caused by a deficiency of what enzyme?
HGPRT (hypoxanthine-guanine
-
What enzyme is involved in the making of uric acid?
Xanthine Oxidas
-
What amino acidpathy mimics the symptoms of Uric acid?
Alkaptonuria
-
Gout is caused by deposition of what?
uric acid
-
Allopurinol action?
Inhibitor of xanthine oxidase
-
What is a competitive inhibitor of Aspartate transcarbamoylase?
Glycine
-
5 Fluorouracil does what?
inhibits thymidylate synthesis
-
Trimethropin does what?
inhibits bacterial dihydrofolate reductase
-
Methotrexate does what?
inhibits bacterial dihydrofolate reductase
-
Ribonucleotide reductase is inhibited by what?
Hydroxy urea
-
What enzyme is used to reduce the 4 ribonucleotides?
ribonucleotide reductase
-
What reducing agent is used to reduce ribonucleotides?
NADPH
-
What is used along with ribonucleotide reductase to reduce ribonucleotide
Thioredoxin
-
What is the result of dATP binding to ribonucleotide reductase activity site?
- decreased catalytic activity
- prevents DNA synthesis
-
Adenosine deaminase deficiency primarily affects what kinds of cells?
Lymphocytes
-
High levels of dATP have what effect?
decreased ribonucleotide reductase activity
-
What chemical prolongs the half life of adenosine deaminase?
PEG --polyethylene glycol
-
What are the enzymes that require vit b 1?
- Transketolase
- pyruvate dehydrogenase
- alpha keto acid dehydrogenase
- branched chain AA dehydrogenase
-
Beri Beri results from a deficiency of what?
Vit b 1
-
BeriBeri results in what?
- Cardiomegaly
- Peripheral neuropathy
- Foot-Drop
- Wrist Drop
-
In alcoholics with vit b1 deficiency you get what?
Wernicke-Korsakoff syndrome
-
Vit B1 and 2 are found where?
Animal Products
-
Deficiency of Vit b2?
2 C's
- Chelosis
- Corneal Vascularization
-
What does Folate carry/Transfer?
methyl
-
What is checked at end of G1 phase?
pre-replicative damage
-
Is the pentose sugar or the nitrogenous base labeled with the " prime" symbol?
pentose sugar
-
What kind of bond connects the phosphate in a nucleotide?
ester bond
-
What are the precursors of purine?
glycine, CO2, N-10 tetrahydrofolate, glutamine, aspartate
-
What is the rate limiting step in de novo purine synthesis?
glutamine PRPP amidotransferase
-
What activates Glutamine PRPP amidotransferase?
Pi
-
What inhibits Glutamine PRPP amidotransferase
purine nucleotides
-
Sulfanamides inhibit what?
synthesis of Folate
-
What is the mode of action of Sulfanamides?
- PABA analog
- blocks Dihydropteroate synthase
-
Trimethropin inbihits what?
dihydrofolate reductase
-
Methotrexate inhibits what?
Human dihydrofolate reductase
-
Conversion of IMP to AMP requires what type of high energy molecule?
GTP
-
Conversion of IMP to GMP requires what type of high energy molecule?
ATP
-
Mycophenolic acid blocks what enzyme?
IMP dehydrogenase
-
What drug is used in preventing graft rejection?
Mycophenolic acid
-
Degradation of nucleic acids produces what?
Uric acid
-
Hypoxanthine-guanine phosphoribosyltransferase uses what two precursorse to produce IMP and GMP?
- Hypoxanthine + PRPP--->IMP
- Guanine + PRPP----> GMP
-
How are dietary sources of vitamin A absorbed?
- esters are broken down into retinol
- retinol is absorbed
- retinol is esterified into esters
-
Lipid soluble vitamins are carried how from the intestinal cell?
in the chylomicron
-
Too much retinoic acid causes what?
tumor
-
Are teratogens mutagens?
no
-
Examination of what PTH derivative establishes its presence?
PTH (35-84)
-
How does calcium exist in plasma?
- 50 % free (ionized)
- 50% protein bound
-
How does a malignant myeloma cause hypercalcemia?
causes PTHrp
-
What are the 2 signs of Hypocalcemia?
- Trusseau's sign
- Chvostek's sign
-
Hypocalcemia in kids?
Rickets
-
Hypocalcemia in adults?
osteomalacia
-
What is the abreviation of dicarboxylic glutamate?
GLA
-
What is the rate determining step in purine synthesis?
Glutamine-PRPP amidotransferase
-
What inhibits xanthine oxidase?
allopurinol
-
What prevents reabsorption of uric acid in the PCT?
probenecid
-
Glutamine-PRPP amidotransferase is inhibited by?
IMP, GMP, AMP
-
IMP dehydrogenase is inhibited by?
GMP
-
Adenylosuccinate is inhibited by?
AMP
-
What deoxyribonucleotide inhibits Ribonucleotide reductase?
dATP
-
What stimulates the activity of Ribonucleotide Reductase?
ATP
-
Hydroxyurea blocks what enzyme?
ribonucleotide reductase
-
Severe combined Immunodeficiency diseases is caused by a deficiency of what enzyme?
adenosine deaminase
-
What accumulates in Adenosine Deaminase deficiency?
dATP from adenosine
fyi..adenosine + PRPP-->AMP-->ADP-->dADP--dATP
-
What is the consequence of accumulated dATP on Nucleotide synthesis?
- dATP inhibits Ribonucleotide Reductase--> no nt
- no nt--> low division of cell especially..lymphocytes
- -->immuno-suppressed
-
What extends the life of AD?
PEG
-
What is the rate limiting enzyme pyrimidine synthesis?
carbamoyl phosphate synthase II
-
What two sources give rise to a pyrimidine ?
- Aspartate
- carbamoyl Phosphate
-
What enzyme converts dUMP to dTMP?
Thymidylate synthase
-
What drug binds to thymidylate synthase and thus preventing the conversion of dUMP to dTMP?
5 Fluoro Uracil (5FU)
-
What is the methyl donor in the conversion of dUMP to dTMP?
N5N10 methylene tetrahydrofolate
-
CTP synthase is inhibited by what?
activated by what?
-
What drugs allows for suicide inhibition?
5-FU
-
Methotrexate and Trimethropin are what type of inhibitors?
competitive
-
What are the degradation products of Pyrimidines?
- Thymine--->methylmalonyl coA-->succinyl coA
- Uracil---->acetyl coA
-
Receptors for steroid hormones, thyroid and retinoic acid have what 2 domains on the intracellular receptors?
- ligand binding domain for the hormone
- DNA binding domain
-
Gs protein is also called what?
Gprotein
-
Which subunit of a Gs protein has GTPase activity?
alpha
-
What subunit of the G protein detaches with the GTP and binds to AC?
alpha
-
Phosphorylation takes place on what a.a residue?
serine or threonine
-
What toxin causes ribosylation of the alpha subunit?
cholera toxin
-
What hormones act thru the Gi proten?
- acetylcholine
- ATII
- somatostatin
-
What calcium binding protein is used intracellularly?
calmodulin
-
Receptor for what hormone has intrinsic kinase activity?
- Insulin
- GF
- GH
- PDGF
- VEGF
- Prolactin
-
How does mutated ras gene cause uncontrolled proliferation?
alpha s subunit is constitutively active
-
What 2 toxins cause ribosylation of alpha s subunit?
By what mechanism is the cholera brought on?
- cholera
- E.coli----no degradatation of GTP to GDP
- phosphorylation of CFTR channel--loss of Cl
- water follows--->diarhea
-
Proinsulin to insulin cleavage occurs where?
in the Golgi Apparatus
-
Which 2 G.I hormones stimulate the release of Insulin?
- cholecystikinin
- Gastric Inhibitory Protein
-
What is the mechanism of insulin secretion after glucose uptake?
- glucose metabolized--> high ATP
- High ATP---> prevents efflux of K+
- high Intracellular K+---> depolarization
- depolarization-->Ca influx
- Ca influx---> fusion of vesicle with PM
-
What effect does insulin have on HMP shunt?
it promotes it b/c in fed state you can allow urself to maintain upkeep..which HMP shunt does by producing NADPH and Ribulose-5-phosphate
-
What is the a.a chain length of insulin?
Glucagonn
-
Branched chain a.a are primarily metabolized where?
skeletal muscle
-
What are two symptoms of Hypoglycemia?
- Adrenergic---due to epi
- Neuroglycopenia---low glucose in brain
-
What are the 2 regulatory systems that respond to hypoglycemia?
- alpha cells of islets of langerhans--glucagon
- hypothalamus---acth---cortisol
- epinephrine
-
What BMI is overweight?
- overweight-- >25
- Obese class I--- >30
- Obese Class II--- >35
- Obese Class III --- >40
-
Men's obesity is classified as what?
Android
-
Woman's obesity is classified as what?
Gynecoid
-
What type of obesity, Android or Gynecoid has worse health consequences?
Android
-
Why do men tend to loose faster?
- because the abdominal fat(android) has a
- - higher turnover rate
- - more hormone sensitive
-
Leptin is produced by what cells?
Adipocytes
-
What action does leptin have on the hypothalamus?
leptin inhibits hunger center in the brain
-
Nutritional hormones relay to what part of the brain?
Hypothalamus
-
What 2 nuclei in the hypothalamus control fuel intake and metabolism?
-
What hypothalamic nucleus stimulates eating?
orexigenic
-
Orexigenic nucleus secretes what peptide to stimulate eating?
neuropeptide Y
-
Anorexigenic nucleus produces what signal that prevent eating?
alpha-MSH
-
Is Leptin appetite stimulating or inhibiting?
leptin is appetite inhibitng
-
Is ghrelin appetite stimulating stimulating or inhibitng?
appetite stimulating
-
Which neurons, orexigenic or anorexigenic are inhibited by leptin?
orexigenic---neuropeptide Y
-
TNF-alpha has what effect on insulin resistance?
increases insulin resistance
-
What effect does PYY-36 have on the appetite?
in inhibits it
-
What 3 hormones inhibit the orexigenic neurons from releasing neuropeptide Y?
-
What are the 3 components of metabolic syndrome?
- Dyslipidemia
- glucose intolerance
- insulin resistance
-
How does insulin resistance lead to dyslipidemia?
- hormone senstitive lipase is not inhibited by insulin
- HSP breaks down TAGs
- increases of FA and cholesterol
-
What does orlistat do?
prevents release of pancreatic and gastric lipase
-
What does subatramine do?
serotonin and norepinephrine reuptake inhibitor
-
Prothrombin Time (PT) tests which clotting pathway?
Extrinsic
-
PTT tests which clotting pathway?
Instrinsic
-
What receptor does Insulin and Growth hormone use?
associated tyrosine kinase
-
What receptor do growth factors like PDGF, Insulin?
Intrinsic tyrosine kinase
-
What receptor uses JAK/STAT?
associated tyrosine kinase
-
15-17 translocation produces what condition?
Acute Meylegenous Leukemia
-
11-22 translocation produces what cancer?
Ewing's sarcoma
-
11-14 translocation produces what cancer?
Mantle cell Lymphoma
-
Koilychia and dysphagia are caused by what?
iron deficiency anemia
-
What effect do nitrates have on hemoglobin?
nitrates oxidize ferrous iron to ferric
-
What is responsible for the polymerization of HbS?
hydrophobic interactions between the globin genes because of the valine instead of the glutamate
-
What is the antidote for cyanide poisoning?
administration of nitrites b/c nitrites oxidize hemoglobin to methemoglobin which binds CN- with high affinity sequestering it from the mitochondria
-
Radiation has what 2 effects on cells?
- introduces double strand breaks
- produces free radicals
-
The most abundant amino acid in collagen?
glycine
-
During exercise what metabolite stimulates the breakdown of glycogen?
Ca
-
Disulfide bond is an example of what type of protein structure?
super-secondary
-
Where does CO2 bind on a hemoglobin molecule?
amino terminal of
-
Which hemoglobin form T or R has higher oxygen affinity?
R
-
Alport's syndrom is due to what?
abnormal type IV collagen
-
What are the 3 symptoms of Alport's syndrome?
- nephritis
- deafness
- ocular disturbances
-
What is an example of super-secondary structure?
- Leucine-zipper
- Zinc-finger
- Helix-turn-helix
-
Proteins with super-secondary protein structures usually perform what function?
Transcription factors
-
Proteins with sequences are degraded ubiquitously without selection?
PEST sequences
-
Digestion of what is mostly affected in cystic fibrosis?
fat---steatorhea
-
Which monosaccharide is not dependent on sodium- monosaccharide synport?
Fructose
-
What activates trypsin?
enterokinase/enteropeptidase
-
What is the mode of action of orlistat?
blocks gastric and pancreatic lipases
-
Gamma glutamyl transferase is used for what?
amino acid transport across the cell membrane of the intestinal cell
-
What traps the glucose in the cell?
phosphorylation via glucokinase
-
What effect does HPV have on p53?
E6 protein degrades p53
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