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Metabolism 70-75
Cederbaum (3 of 5)
60
Biochemistry
Graduate
08/10/2011

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Cards

Term
Functions of cholesterol (4).
Definition

1)Stabilize membranes,

2)Make bile salts to digest fat,

3)Synth vit E/A/Ubiquinone,

4)Precursor of steroid hormones.

Term
What are the sources of C atoms for cholesterol synth.
Definition
AcCoA from glucose, FAs, AAs, even alcohol.
Term
How does insulin effect HMGCoA reductase?
Definition
deP/activates as well as increases txn via SREBP.
Term
How do LDLs promote CV disease?
Definition
Immune response --> macrophage uptake --> foam cells --> swelling/inflammation
Term
Where in cell and in which tissues is cholesterol synth?
Definition
Cytosol/ER of all tissues, esp liver.
Term
Rate limiting step of cholesterol synth and how is it regulated?
Definition

HMGCoA Reductase (HMGCoA+2NADPH-->Mevalonate+NADP);

inhib by AMP, cholesterol, glu;

stim by insulin, ATP.

Term
How are serum cholesterol levels regulated?
Definition
Uptake of LDL into cells by LDL receptors, receptor mediated endocytosis.
Term
Treatments to lower cholesterol?
Definition

HMGCoA reductase inhibiting statins,

Positively charged bile salt resins.

Term
How do bile salt resins lower cholesterol?
Definition
Bind bile salts which are then excreted causing body to synth more from cholesterol.
Term
How do cells protect against ROS?
Definition
Protective enzymes (incl superoxide dismutases, catalase, glutathione peroxidase) & non-enzymatic mechanisms (GSH, NADPH, vit E, vit C)
Term
Why is a free radical reactive?
Definition
Unpaired e- in outer orbital wants to pair up w another e- to achieve stability.
Term
How are ROS produced in RBCs?
Definition
Nonenzymatic oxdn of hemoglobin, certain drugs/foods.
Term
What types of damage do ROSs cause to cells?
Definition

Proteins-inactivate enzymes, promote, aggradation, degradation.

Lipids-lipid peroxidation, oxidation of polyunsaturated lipids which destroys mbrnes (destroys pmf!).

DNA/RNA-cleaves phosphodiester bond, base-mispairing.

Term
What is lipid peroxidation?
Definition
Peroxidation of many lipids to form lipid radicals + lipid aldehydes
Term
Why is glutathione the most abundant chemical in cells?
Definition
Most important antioxidant! 1)Reqd co-factor for glutathione transferase enzyme, 2) can react directly w some ROS to detoxify.
Term
Which ROS is the most powerful oxidant?
Definition
Hydroxide (OH. @ physio pH)
Term
At which step are most super oxide radicals from the respiratory chain produced?
Definition
Ubiquinone/CoQ step = Q + e- --> QH. + e- --> QH2
Term
Role of cyto p450?
Definition
Removes toxins in liver via it's heme w bound iron - produces some ROS.
Term
Why is brain prone to oxidative damage?
Definition

1) Monoamine oxidases remove nts but produce lrg amts of H2O2,

2) Brain is high in iron --> Fenton rxn --> hydroxyl radicals.

Term
ROS enzymatic protectants?
Definition
SODs, Catalase, Glutathione (req selenium)
Term
ROS biochemical protectants?
Definition
GSH, VitE, VitC
Term
How do VitC/E/GSH work together to fxn as antioxidant?
Definition

Vit E donates H and becomes radical itself --> either:

a) 2 E radicals excreted or

b) VitC will restore.

Then either a) 2 VitC radicals excreted or

b) Glutathione restores and -->GSSG.

Term
When is iron toxic?
Definition
When exceeds ferritin's binding capacity (most iron stored w ferritin, an iron storage protein)
Term
What are 2 beneficial axns of oxygen radicals?
Definition

1)activated under conditions of low oxidant stress to prevent high levels of oxidant stress,

2) NADPH oxidases in macrophages&neutrophils --> respiratory burst.

Term
What is result of NADPH oxidase deficiency?
Definition
Chronic Granulamatosis. Missing-->die w/i 1mo. Deficiency-->incr suscebtibility to disease/tumors.
Term
How does asbestos cause damage?
Definition
Contains iron --> elastase in lung tissue v sensitive to ROS.
Term
What is hemochromatosis and how is it treated?
Definition
Iron overload; by adding iron chelator (desferrioxamine) which prevents iron from entering Fenton pathway.
Term
Which neurogenerative diseases are caused by oxidant damage?
Definition
Parkinsons, Alzheimers.
Term
How does ischemia reperfusion cause injury?
Definition

During prolonged ischemia ATP is broken down producing xanthine. Normally xanthine dehydrogenase oxidases xanthine to NADH but under stress and because of the new availability of O2 (from reperfusion) it is converted to xanthine oxygenase which still forms NADH but using O2 (rather than NAD+) as cofactor --> results in superoxide radicals.

In addn QH2 has accumulated due to resp chain back-up.

Term
How can ischemia reperfusion injury be prevented?
Definition
Addition of antioxidants (ie C, E, chelators, glutathione) to reperfusion soln.
Term
Functions of AAs.
Definition

1)Synth new protein,

2)Synth regulatory enzymes in response to metabolic conditions,

3)Synth nitrogeneous metabolites,

4)Provide energy via their degradation,

5)Provide Cs for gluconeogenesis and FA synth.

Term
What does a pos or neg nitrogen balance signify?
Definition
Pos=N intake>excretion (growth, pregnancy; Neg=intake
Term
Which proteins have slow turnover rates? Fast?
Definition
Slow = structural proteins, tissues; Fast = hormones, digestive enzymes, nts, rate limiting enzymes, oxidized proteins from ROS rxns.
Term
Fxn of ubiquitin.
Definition
Tags protein for degradation.
Term
What is major cofactor for AA metabolism and what is its function?
Definition
B6=Pyridoxal Phosphate, transfers amino grp from AA-->aKG to form Glutamate + aKetoAcid.
Term
How are AAs used as an energy source?
Definition

Degraded to pyruvate, AcCoA, TCA cycle intermediates --> 1)oxidized,

2)converted to glucose & stored as glycogen, or

3)converted to FAs& stored as adipose triacylglycerols.

Term
Importance of transamination in AA metabolism?
Definition
Removes amino grp from AAs to collect into a common pool as glutamate which can then enter the urea cycle for detoxification.
Term
Clinical significance of GOT/GPT?
Definition
Presence in blood signifies tissue damage, esp liver.
Term
Which are the essential AAs?
Definition
PVT TIM HALL (Phe, Val, Trp, Thr, Iso, Meth, His, Arg, Lys, Leuc)
Term
Rxn catalyzed by Alanine Amino Transferase? Opposite rxn?
Definition
Alanine+aKG-->Pyruvate+Glutamate; opp via Glutamate Pyruvate Transaminase (GPT).
Term
Rxn catalyzed by Aspartate Amino Transferase? Opposite rxn?
Definition
Aspartate + aKG --> OAA + Glutamate; opp via Glutamate Oxaloacetate Transaminase (GOT).
Term
What are the 3 nitrogenous excretory products of the body?
Definition
Uric acid, creatinine, ammonia.
Term
How is excess amino nitrogen excreted?
Definition
Collected as glutamate --> glutamate releases amino grps as ammonia --> enters urea cycle in liver --> excreted.
Term
What are the 2 diff carbamyl phosphate synthetase rxns and where in cell do they occur?
Definition
CPSI-->1st/RLS of urea cycle (CO2+NH4+2ATP-->Carbamoyl Phosphate+2ADP),mito; CPSII-->pyrimidine synth, in cyto.
Term
Why is ammonia toxic?
Definition
1)NH3 is basic-->incr blood pH, 2)Combines w aKG-->Glutamate which reqs pulling aKG outa Krebs, 3)Combines w Glutamate-->Glutamine which is an excitatory nt.
Term
Symptoms of ammonia intoxication?
Definition
GI irritability, N/V, lethargy, neurological disturbances, coma, death.
Term
Is arginine essential and why?
Definition
Not in adults bc Arginosuccinate-->Arginine+Fumarate (urea cycle).
Term
What is cyclical about the urea cycle?
Definition

Last step is arginine-->urea+ornithine,

ornithine re-enters cycle via ornithine+carbamoylP-->citrulline+Pi.

Term
What mito exchange transporter is reqd for urea cycle?
Definition

Citrulline for Ornithine.

Ornithine needs to get into mito to combine w Carbamoyl P from CPSI rxn, Ornithine+CarbamoylP-->Citrulline, Citrulline mito-->cyto to enter urea cycle.

Term
What is BUN?
Definition
Blood Urea Nitrogen, diagnostic for kidney fxn since kidney filters & removes urea.
Term
What is most common inborn error of metabolism of urea cycle?
Definition
OTC (Ornithine TransCarbamylase) def.
Term
How can ammonia toxicity be prevented if someone has a urea cycle enzyme def (4)?
Definition

1)Low protein diet,

2)maintain blood pH w acetate, which is acidic,

3)clean gut of bactera,

4)benzoate/phenylacetate remove glycine/glutamine, taking NH3 with it.

Term
How does muscle ammonia get to liver to enter urea cycle?
Definition

In muscle: NH3+Glutamate-->Glutamine (via Glutamine synthase)-->blood-->

In liver: Glutaminase hydrolyzes --> Glutamate+NH3,

NH3-->urea cycle,

Glutamate+NADP-->aKG+NADPH+NH3 via glutamate dehydrogenase.

Term
Is glutamate an essential AA? Why or why not?
Definition
No, can be produced via reversible glutamate dehydrogenase rxn in liver: Glutamate+NADP<-->aKG+NADPH+NH3
Term
What will be found in high levels in the blood after a high protein meal?
Definition
Glutamine & Glutamate, carrying a-Amino grps muscle-->liver.
Term
Where do first 2 steps of urea cycle occur? Last 3?
Definition
1st 2 in mito, last 3 in cyto.
Term
Energetic cost to push 1 NH3 thru urea cycle?
Definition
4 P-bonds
Term
What can assaying ammonia level in blood tell us?
Definition
Liver dysfunction
Term
How is CPSI regulated?
Definition
Activated by NAGA, whos synth from glutamate + AcCoA is activated by arginine.
Term
How are the urea cycle and citric acid cycle linked?
Definition

Fumarate-->malate (hydration) --> OAA (oxidaton); OAA-->1)+AcACoA-->citrate-->Krebs,

2)gluconeogenesis,

3)pyruvate,

4)aspartate via transamination-->urea cycle.

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