open questions Flashcards
substrates + cofactors for methyl malonyl Coa mutase
L-methylmalonyl –> succinyl Coa
cofactor: B12
what organs will be affected by glycogen storage disease
skeletal m + liver
position of the OH group in primary bile acids + config
(3,7,12) alpha- outward position
threonine dehydratase. cofactor and sub + prod
threonine –> a-ketobutyrate
cofactor: PLP
get free NH3 !!!
precursors of LDL, what enzyme?
IDL, hepatic lipase
enzymes in FA synt that reduces NADPH
b-ketoacyl ACP reductase
enoyl-ACP reductase
enzymes that covalent modi PDH
pyruvate DH kinase - inhibits PDH
pyruvate DH phosphatase - activates PDH
what does PP1 do?
activate glycogen synthase (by dephosphos) inhibit GP (by depos), GPK
what does phosphoglucose mutase
G-6-P –> G-1-P
UMP synthase - reaction
UMP synthase consist of both orotate phosphoribosyl transferase and OMP decarboxylase.
Orotate –> omp –> UMP
need PRPP and get CO2
hydroxybutyrate DH reaction + cofactor
b-hydroxybutyrate –> acetoacetate
need NAD+
what is the low affinity glucose transporter?
GLUT-2
what does glycogen phosphorylase
glygocen –> G-1-P
what kind of nucleotide binding site does muscle glycogen phosphorylase have?
AMP
common cofactors required for both a-KG DH and pyruvate DH
TPP (E1) Lipoid acid (E2) CoA-SH (E3) NAD (E3) FAD (E3)
which reaction is catalyzed by UDP-glucose pyrophosphorylase?
G-1-P –> UDP-glucose
enzymes req for transport of long chain FA into mitochon
Acyl Coa synthase
CAT1
CAT2
(Translocase)
how many FADH2 is prod per palmitate (16C)?
7 FADH2
2 diff cell receptors in cholesterol uptake in hepatocytes
SR-B1
LDL receptors
major intracellular target of statins?
HMG Coa reducctase
ALAT
Alanine –> pyruvate
w/help of a-KG –> glu
Glutamate DH
Glutamate –> a-KG
w/ NADPH+ H2O –> NADP + NH3
enzyme blocked in fructosesuria
Frucotse kinase
enzyme blocked in fructose intoleranse
Aldolase B
Pyruvate carboxylase, substrate, prod + cofactors
Pyruvate –> Oxaloactetate
cofactor: biotin, Mg2+
Acetyl CoA carboxylase - function + cofactor
Acetyl Coa –> malonyl CoA
Cof: Biotin
name an ionophore that uncouples proton pumping for ATP synthesis in mitochondria.
DNP-2,4-dinitrophenol
Cholesterol uptake by liver
LDL+IDL transport cholesterol to LDL-receptors
HDL takes up excess cholesterol and brings it into the liver via SC-B1
Adenylyl cyclase reaction
ATP–> cAMP + Pi
Which cell have GLUT 2?
Pancreatic B-cells
Liver
Potassium ion is located in ____ of potassium ion chanel
Selectivity filter leading to the central cavity
Enzyme for glucoronidation?
UDP-glucuronosyltransferase (UGT)
What type of HDL component is resp for atherosclerosis?
Defective Apo-A1
CFTR is phosphorylated by what?
PKA
how do you inhibit NE
MAO, COMT
Biotransformation phase II reactions
Glucoronidation, sulfatation and glutathione
What can be detected in urine during metabolism of dopamine?
Homovanilic acid (HVA)
What can be detected in urine during metabolism of serotonin?
5-hydroxy indolence acid/monoamide oxidase
What can be detected in urine during metabolism of NE
MHPG and VMA
Primary target for Quabain/strophantine?
inhibition of Na+/K+ ATPase
how do we inhibit Na+/K+ ATPase?
Quabain/strophantine
the open probability of ion channels range from?
0-1
treatment of diabetes mellitus, how?
By sulphonylureas - these binds to the SUR unit and depolarize the insulin from the beta cells.
under normal condition ATP-sensitive K+ channels are activated by and inhibit by?
Activated by: ADP, Diazoxide
inhibited by: ATP, sulfonylureas
how is fibrinolysis terminated?
PAI 1/2, a2 antiplasmin a2 macroglobulin
clearance of fibrinolytic factors through liver
substrates for thrombin
anticogagulant:
- T+heprain –> ATIII
- T+TM –> protein C
Procoagulant:
- T+TM –> TAFI
- T+fibrin –> XIII
- T+PLT –> V,VIII,XI, PAR
- Fibrinogen –> fibrin
what is the dominant reaction in the first phase of biotransformation?
Oxidation - performed by cyp p450
what kind of metabolizer phenotypes are known due to SNP-s of drug metabolizing enzymes?
Poor metabolizer/extensive metabolizer
which enzymes catalyzes glucoronidation?
UDP-glucoronosyltransferase
wha kind of DNA binding domain is characteristic for steroid-thyroid-retinoid receptors?
Zinc-finger binding domain
which phase of biotransformation is mediated by transporters?
Phase 3 - multidrug resistant transporters
which are the most important xenobiotic inducer of CYP1 isoenzyme?
PAHs
What inhibits blood coagulation at sites of vessel wall injury?
Protein C - it binds w/thombin and TM.
List 3 triggers of platelets
ADP, thombin, PAF, Thromboxane A2
Malic enzyme - sub+prod+cofac
malate –> pyruvate
makes NADPH!!!!!
absence of which enzyme causes accumulation of methyl malonyl CoA?
methyl malonyl coa mutase
What enzyme is deff in orotic aciduria?
UMP-synthase
which consist of dihydroorotate DH and rotate phosphoribosyl transferase
role of GLUT-2 and glucokinase
both of them have high KM and low aff to glucose.
both regulate insulin secretion.
name a transcription factor/protein that initiates transcript:
TATA box binding protein
name a transcription inhibitor
rifampicin (only prokaryotes), actinomycin D(both), a-amatin (eukary)
activity of telomerase
reverse transcriptase - add to the free 3’end
which protein binds to the 5’cap during eukaryotic translation initiation?
eIF4
from which vitamin does CoA derive from?
B5
which metal ion can be found in the structure of vitamin B12?
Cobalt
what is the fundamental difference between senescent and quiescent cells?
sensescent = have stopped dividing! quiscent = cell cycle is postponed. cell is in non-dividing phase.
name at least 3 potential coenzymes for DH enzymes.
CoA, NAD+, FAD+
what binds the central position of hemoglobin?
Heme
what are the proteins of mismatch repair?
MutS, MutH, MutL
what enzyme adds the cap to mRNA?
Cap methyltransferase
what sorts of bonds get disrupted in case of DNA denaturation?
H-bonds and non covalent bonds between base pairs.
It destroys the secondary and tertiary structure.
how many 2,3 BPG molecules are bound to a single myoglobin molecule?
none. its not bound to myoglobin but to hemoglobin.
how dooncogens of DNA tumor viruses promote tumor formation?
they inhibit tumor suppressor proteins (ex.p53)
what is the characteristic structure of silk fibrin?
beta pleated sheets.
what is the secondary structure of collagen?
collagen helix
role of zinc fingers
transciption factors
direct targets of p53
p21, BAX, cyclin B
2 inhibitors of G/S checkpoint of cell cycle
p53, p21, Rb
2 inhibitors of G2/M checkpoint of cell cycle
ATM, Chk1, p53
3 proteins involved in DNA repair
endonucleases, DNA polymerase, DNA ligase
what is wobble principle?
that one AA might be coded by more than one codon!!
the third position
role of the mRNA cap
help mRNA bind to ribosome + stability
what checkpoint in the cell cycle are not controlled by embryonic stem cells?
G1/S
types of DNA repair systems
mismatch repair, base excision repair, nucleotide excision, recombinant DNA repair.
what is produced in the zona glomerulosa?
produce and secrete mineralocorticoid aldosterone
hyperuricemia - which enzyme?
HPRT - lesch-Nyhan syndrome.
cogenital adrenal hyperplasia?
defect in cyt P450
3 ways to decrease blood cholesterol levels:
inhibition of HMG-Coa reductase by statins.
activation of LCAT
increase LDL receptors.
Metabolic effects of LXR
LXR will sense oxysterol (which is a oxidized form of cholesterol). (so if we have a lot of oxysterol we will also have a lot of cholesterol, this mechanism is to decrease the cholesterol in the cel)This will regulate transcription factors:
CYP7A1 - increased bile acid synthesis
ABCA1 - increased cholesterol efflux
IDOL - decreased LDL receptors.
what happens to glycolysis during hypoxia?
it increases (this is determined by PFK1. )
what enzyme produces GTP in TCA cycle?
succinyl CoA synthase.
give at least two functions of peroxisomes
B-oxidation of very long-chain fatty acids.
oxidation of alcohol to acetaldehyde
what are the functions of SR-B1?
the scavenger receptors are involved in uptake of cholesterol esters from HDL.
what enzyme catalyze the formation from testosterone –> estradiol? what group of enzymes does it belong to?
aromatase.
CYP 450 superfamily of monooxygenases
what causes phenylketonuria?
deficiency in Phe hydroxylase
which amino acids have negative charge at ph=7?
Asp, Glu
which amino acids have no charge at ph=7?
Tyr, Ser, Cys
which amino acids have positively charged (polar) side chains at pH=7?
Lys, Arg, His
What are the essential AA?
His, Ile, Leu, Lys, Met, Phe, Trp, Thr, Val
Just remember: I Like To Teach His Mad Vets Lumbar Puncture
what is the turnover number?
Mol(product)/mol(enzyme) x sec
what is in the active site of serine proteases?
His, Ser, Asp
what is Km?
the substrate concentration, where we can measure the half of the maximum speed.
Vmax?
at high substrate concentration all enzymes are in enzyme-substrate complex therefore the speed of the enzyme reaction has reached its maximum value (Vmax)
inhibitors of F-1,6 BPase
AMP/ADP and Fru-2,5-BP
Glutathione consist of which AAs?
Glu-Cys-Gly
Which protein can regulate/phosphorylate the CFTR channel?
cAMP dependent protein kinase
which enzymes are needed to make dihydroorotate from Gln and Asp?
CPS II
Asp transcarbamoylase
Dihydroorotase
write the reaction for fatty acid activation
S: Fatty acid+ATP+Hs-CoA
P:acyl-Coa + AMP + 2Pi
E: Acyl Coa synthase
for the testosterone receptor, which has the highest affinity, testosterone or dihydrotestosterone
Dihydrotestosterone
Probability for an ionchannel
can range from 0 to 1
Von Gierkes disease
Glycogen storage disease
Glucose-6- phosphatase
List 3 regulators for HMG-Coa reductase
Statins
Cholesterol (neg.feedback via Serb-Scap)
AMP activated protein kinase.
What is the function of SR-B1?
Scavenger receptor. Involved in uptake of CE from HDL
List the mechanism which can cause an increase in intracellular Ca level and name the molecules responsible for this.
IP3, Strophantine
Ach >IP3>increased Ca2+
Strophantine inhibits NA-K ATPase
Na-Ca reversal
Name 2 eicosanoids
Thromboxane A2
PGE1
PCI2
At least two function of peroxisomes
- Beta oxidation of very long chain fatty acids
- Oxidation of alchohol to acetaldehyde
- Production of plasmalogen (in myelin)
- Contains catalase which oxidizes H2O2
Causes for increased free FA in serum:
Diabetes
Starvation
Heavy exercise
Targeted channel protein in Myasthenia Gravis
nicotinic Ach receptor at NMJ
Which are the most important ligands of nuclear receptors?
Mineralocorticoid, glucocorticoid, progesterone, androgen, estrogen, drugs
Which are the three most common types of DNA binding domains found in intracellular receptors?
- Zinc finger binding domain
- Leucine zipper
- Helix-turn- helix
Name at least 3 serine protease examples
Chymotrypsin, Trypsin, Elastase
What enzymes are deficient in hyperurocemia
- Glucose-6-phosphatase deficiency
- HGPRT: hypoxanthine-guanine phosphoribosyltransferase deficiency
- Elevated 5’-phosphoribosyl-1’-pyrophosphate synthetase (PRPP synthetase)
If there is an excessive citrulline, which enzymes are deficient?
Arginosuccinate Synthetase
Way to reduce cholesterol blood level
- Statins
- Cholestrol free diet/ lifestyle
- Decrease LDL receptors
- Activate LCAT
- RESINS
What enzyme deficiency causes immunodeficiency?
ADA : Adenosine Deaminase
Monosaccharide unit and bond type of lactose, glycogen, sucrose
Glycogen: glucose- glucose a(1>4) + braches a(1>6)
Lactose: glucose – galactose b(1>4)
Sucrose: glucose- fructose a(1>b2)
Which enzymes do CYP11B2 encodes for?
11-OHase, 18OHase, DH aldosterone synthase
Which enzymes do CYP11B1 encodes for?
11-hydroxylase
Which enzymes do CYP17A1 encodes for?
17OHase and 17,20 lyase
What are cytochromes P450 involved in?
- production of steroid hormones
- metabolism of FA, prostaglandins, leukotriene and retinoids.
- inactivation of therapeutic agents.
- conversion of chemical to highly reactive molecules that may produce unwanted cellular damage.
- enzyme inhibition or induction resulting in drug-drug interactions and adverse effects.
Name 3 AA that can form pyruvate.
CYS, SER, ALA
Which enzymes functions in both glycolysis and gluconeogenesis?
phosphoglucoisomerase, aldolase B+A, glyceraldehyde 3-P, phosphoglycerate kinase, phosphoglycerate mutase, enolase
What are the irreversible steps in glycolysis? (name the enzymes)
HK/GK, PFK1, pyruvate kinase
what are the enzymes for gluconeogenesis?
Pyruvate carboxylase, PEPCK, fructose-1-phosphatase, glucose-6-phosphatase