Work Groups AND Quizzes

Question 1

The … form of iron can bind oxygen

Answer 1

Ferrous (Fe2+)

Question 2

How does bortezomib inhibit catalytic residue of proteasome

Answer 2

Boron (metal) in molecule
Chymotrypsin is meant to cleave peptide bond, and boron atom lies in from of this > binding catalytic N-terminal threonine in beta subunit proteasome
> coordinate bond: bond between metal and ligand
> bond acts like covalent bond but falls apart after a while (not stable: two electrons from bond come from metal and none from oxygen)
> reversible
> competitive inhibitor
> IkB not degraded, NFkB not active

Question 3

Blood brain barrier contains endothelial cells which express

Answer 3

GLUT1

Question 4

C-peptide and insulin

Answer 4

In proinsulin > C-peptide connecting peptide and chaperone for the protein to bind
> has 3 disulfide bridges
> released upon activation of human made insulin (not injected) (measurement parameter)
> linker peptide A and B chains in proinsulin

Question 5

What is so important for iron and metals as electron transporter

Answer 5

It can accept one electron instead of two (as for carbons, hydride ion)
> iron-sulfur clusters in the respiratory chain enzymes

Question 6

Fenton reaction

Answer 6

Fe2+ + H2O2 > Fe3+ + OH- + *OH (hydroxyl radical)
> ROS which cannot be neutralized > ferropsosis
OH will attack the first molecule that it encounters.
Previous
iron can easily gain or lose electrons and bind oxygen in ferrous state
> O2 single electron reduction to superoxide O2-
> superoxide dismutase makes H2O2 from it
> if H2O2 accepts electron, hydroxyl radical.

Question 7

How is iron taken up from diet

Answer 7

Ferric reductase (vitamin C) on border duodenum reduce ferric iron to ferrous iron.
Uptake ferrous iron (free, from plants) by Divalent metal transporter 1 (DMT1, can also take up Mg2+)
Uptake ferrous iron bound by heme (from meat) by heme carrier protein 1 (HCP1)
> enterocytes
Ferrous iron released into body by ferroportin
Hepaestin oxidized iron to ferric iron
Transport ferroportin across basal membrane to blood
in blood, ferric iron binds transferrin
the rest we know

Question 8

Mutation HFE can lead to

Answer 8

Binding transferrin receptor and too much iron uptake

Question 9

RNA pol II is a … enzyme

Answer 9

processive

Question 10

Processive enzyme glycogen synthase

Answer 10

Product of catalysis is held, not released, and new substrate UDP-glucose binds
> primer for GS is the glycogenin with a little piece of a-1,4-glucan

Question 11

Making carbamoyl phosphate from ammonium and bicarbonate costs 2 ATP total. Why?

Answer 11

-Hydrated CO2 (carbon dioxide) is an acid (CO2 is a base) > in water: CO2 + H2O > H2CO3 (carbonic acid)
-Bicarbonate (HCO3-) > important for pH in blood
-First activation of bicarbonate using ATP > add a phosphate > carboxyphosphate
-HCO3- + ATP > bicarbonate carboxyphosphate
-Carboxyphosphate + NH4+ > carbamate + Pi
-Activate it to then add it to orthinine (every reacion: activation)
Carbamate + ATP > carbamoyl phosphate.
> 2 ATP needed > 2 times activation: of the carbon and of the carbamate to make citrulline

2: NH4+ + HCO3- + 2 ATP > carbomoyl-P + 2 ADP + Pi (carbamoyl-phosphate synthetase)

Question 12

Why is hyperammonia dangerous for the brain

Answer 12

• Too much conversion to glutamate from ammonium > glutamate is neurotransmitter
• High concentration ammonium > gas goes into brain > a lot of glutamate being made: reverse reaction because of concentrations: making glutamate using ammonium > deaminases work in the wrong direction
• No a-ketoglutarate > used to make glutamate > problems in energy metabolism. > TCA cycle flux decreased. It stops: neuron needs energy, not enough energy.
• Depletion alpha-ketoglutarate
• Too much glutamate as neurotransmitter
• Toxic: binds with sodium-potassium chloride pump > activated > too many ions in ions > osmotic flux water inside cell > swell until bursting > necrosis (losing neurons: neurodegenerative disease).

Question 13

What does the pKa value mean

Answer 13

If the pKa=pH than in the reaction for which the pKa is given: ratio 1:1
[base]=[acid]
if pKa < pH: log(base/acid) positive
[base]>[acid]
pH = pKa + log([A-]/[HA])
pH-pKa = log([A-]/[HA])

Question 14

How do high concentrations of lactate in blood create acidosis?

Answer 14

Lactate is a alkaline/base (no lowering pH)
> needs to be converted in liver, transport through blood
> lactate is negatively charged, cotransport H+ to retain voltage across membrane (membrane potential) and charge of the cell
> H+ causes acidosis
> Monocaboxylate transporter (MCT) > always cotransport with H+
> lactate acidosis is nonsense, lactic acid acidosis makes sense

Question 15

Effects carbon monoxide (CO) and cyanide on ATP production

Answer 15

> strongly bind cytochrome c oxidase (complex 4)
stops tranfer of electrons to oxygen
Respiratory chain and ATP synthase stop working
ATP production dependent on anaerobic glycolysis.

Question 16

Lactic acidosis in PC deficiency

Answer 16

• Lactic acidosis in increase in lactic acid in blood
• Lactic acid is an acidic compound causing acidification of blood
• Pyruvate carboxylase is essential part of gluconeogenesis, in deficiency, liver will not be able to make glucose from lactate
• Lactic acid released into the blood by other cell types cannot be processed by the liver and accumulates in blood, causing acidosis
• PDH first converts pyruvate to acetyl-CoA which accumulates because there is not enough oxaloacetate, this inhibits PDH
• Low oxaloacetate and high acetyl-CoA will interfere with TCA cycle in liver
• Lactic acid production by anaerobic muscle (Cori cycle) and red blood cells > release to blood for liver.

Question 17

mechanisms of action aspirin and ibuprofen

Answer 17

2. Apirin transfers its acetyl group to a serine residue in a hydrophobic channel leading to the active site of the cyclooxygenase component of prostaglandin H2 synthase. Ibuprofen is also able to block this channel. Prostaglandins are hormones which promote the inflammatory response (the immune system flow towards a site) after injury or infection which causes pain, fever and swelling (inflammation). These cyclooxygenase inhibitors mitigate the response.

Question 18

What does a partition coefficient of 5 mean for the ADME properties absorption by diffusion?

Answer 18

• Partition coefficient indicates ability of drug to dissolve in membranes and correlates with solubility of a drug in an organic solution. Partition coefficient is determined by log10(P) of the partition in octanol and water. A partition coefficient of 5 means that the concentration of the drug in octanol (hydrophobic) is 100,000 times greater than in water
• Drugs with partition coefficient greater than 5 (P = 5)are hydrophobic and soluble in lipids, but are poorly soluble in water. These drugs are unlikely to be taken up by diffusion.

Question 19

Organ specific gene expression by sequence and structure of DNA

Answer 19

• Enhancers: DNA sequences to which organ specific transcription factors can bind and initiate organ specific transcription programs, by recruiting other transcriptional regulators like co-activators and RNA pol II to initiate transcription.
• Methylation leads to silencing of DNA. Heterochromatin correlates with methylation of cytosines in DNA by DNA methyl transferases

Question 20

Which drug complements bile salt binders (lower cholesterol by inducing bile acid synthesis). Why are only bile salt binders ineffective. Which drug does increase cholesterol excretion in feces.

Answer 20

C: Because there exists a concept called enterohepatic cycling, in which the bile, including the bile acids to solubilize the dietary fats are taken up by the intestines and will be taken up by the liver afterwards. This means that excretion of bile acids doesn’t mean absolute removal of them in the feces, they are partly taken back up.
E: The drug ezetimibe might actually have effect on excretion, since this drug inhibits the reabsorption of the bile by the intestine. This means that the bile acids are absolutely removed and that the cholesterol concentrations are decreasing more significantly when using bile salt binders.
- D: statins, which inhibit cholesterol synthesis in the first place by inhibiting HMG-CoA reductase complement bile salt binders.

Question 21

the ratio of lactate to pyruvate is a good measure for the ratio …

Answer 21

NAD+ to NADH

Question 22

True or false: major reason familial hypercholesterolemia is overproduction VLDL by liver

Answer 22

False, it is defect in LDLR

Question 23

In pyruvate dehydrogenase complex, the electrons from FADH2 are transferred to NADH, why is this strange?

Answer 23

• NADH usually has higher energy content than FADH2, usually, NADH is a stronger reductor than FADH2.
• Higher energy content of FADH2 achieved by way of attachment to PDH complex
• Compare NADH dehydrogenase (complex 1) which pumps protons in respiratory chain to succinate dehydrogenase (complex 2) that does not pump protons