BIOCHEMISTRY- Raymon Videos Flashcards
What is the Nitrogen balance?
Is the normal condition in which the amount of nitrogen incorporated into the body each day exactly equals the amount excreted
What is associated to negative Nitrogen balance?
Protein malnutrition (Kwashiorkor) Dietary Deficiency of even one essential aminoacid Starvation Unconroled diabetes Infection
Positive Nitrogen Balance situations
Growth
Pregnancy
Recovery phase of injury or surgery
Recovery from condition associated with negative nitrogen balance
What are the products of Glucose+ O2?
CO2 + H2O
With a lot of energy release production
Does Glucose+ O2 –> CO2 + H2O occur spontaneously?
Yes, it doesn’t tell how long it will take to happen
Does Glucose+ O2 –> CO2 + H2O occur immediatly?
NO
What determines spontaneous biochemichal reactions?
Energy (Δ G)
What determines speed of biochemichal reactions?
Rate (V)
What increases speed of biochemichal reactions?
By enzymes
What is the Δ G++ energy activation?
Energy that is needed to the highest level on top of reaction until it runs forward
What does Δ G
Thermodynamically spontaneous (energy released, often irreversible)
What does Δ G >0 mean?
Thermodynamically nonspontaneous (energy required)
What does Δ G = 0 mean?
Reaction at equilibrium (free reversible)
What does Δ G0 mean?
Energy involved under standarized conditions
What is the effect of enzymes related to Energy?
Decrease energy of activation, Δ G++
In what does Vmax depend on?
of enzymes (more enzymes more Vmax, less enzymes less Vmax
What does Michaelis-Menton plot determine?
Kinetics of reactions
Parameters on Michaelis-Menton plot
Substrate concetration (what the enzyme digest) V (speed of reaction)--> vmol/sec
Which is the rule of kinetic of reactions?
The more substrate you give the more product make, but there a limit on how much you are going to make per unit of time depending in the number of enzymes
What does the plateu of the curve mean in Kinetic Reactions?
Means saturation, the activity of the enzyme is saturated
What does Km in Kinetic Reactions mean?
Substrate Concetration
How is Km calculated?
Is 1/2 Vmax
What is related to Km?
Affinity
What does Km determines?
How well substrate and enzyme like each other, if they each other that is affinity
Who is irreversible proportional to affinity?
Km
So… ↑ affinity translate as…
↓ Km
And ↓ affinity means…
↑ Km
What determines the affinity of a substrate to an enzyme?
The shape
In what does km depends on?
Number of enzymes
In Michealis Menton plot what does the right shift of the curve means?
+ competitive inhibitor, increased (substrate, Km)
Which drugs shift the curve of Michealis Menton plot to the right?
Competitive inhibitors (Antagonist) just like ACE (-), COX (-) except Aspirin
Which is the only COX (-) that does not shift the curve of Michealis Menton plot curve to the right?
Aspirin
What effect do Competitive inhibitors have on kinetic reactions?
↑ Km, No effect on Vmax
What effect fo Non competitive inhibitors have in Kinetic reactions?
No effect on Km, and decreases Vmax
Characteristic of Non competitive inhibitors
Irreversible
Alternative name for Irreversible
Allosteric (Characteristic of non competitive inhibitors)
Example of non competitive irreversible drug
Aspirin
ACE inhibitors (organo phosphorade)
Cianide, CO
In which situation do we see increased of enzymes?
Gene induction expression–> ↑ Vmax
What is the result of increase of enzymes in kinetic reactions?
↑ Vmax
In kinetic reactionswhat does activation means?
↑ Affinity
What is the effect of ↑ Affinity in kinetic reactions?
↓ Km
In Michealis Menton plot… what shifts the curve to the left?
Activator
In Michealis Menton plot… what shifts the curve up?
Inducers
In Michealis Menton plot… what shifts the curve to the right?
Competitive inhibitors
In Michealis Menton plot… what shifts the curve down?
Non competitive inhibitors
In the old days how was methanol posioning treated?
With ethanol administration
What explains ethanol is used to treat methanol intoxication?
Both are substrates for alcohol dehydrogenase (ADH), with ethanol having a much lower km for the enzyme compare to methanol
This prevents methanol from being converted to formaldehyde, which is toxic and not metabolized further
Which is the selected treatment for methanol or ethylenglycol intoxication?
Use of Fomepizole, old management ethanol
Mechanism of action of Fomepizole
Dehydrogenase inhibitor
Characteristics of paracrine hormones
Are secreted into the interstitial space
Very short half life
Example of paracrine hormones
Prostaglandins and neurotransmitters
Characteristics of Water Soluble hormones
Can’t cross membrane of cells
Receptor in cell membrane
Second messengers often involved (Protein kinase activated)
Protein phosphorylation to modify activity of enzymes (requires minutes)
Characteristics of lipid Soluble hormones
Receptor inside cell
Hormone receptor complex binds hormone response elements (HRE of enhancer regions) in DNA
Can get into the cell
Which hormones are lipid soluble?
Steroids, Calcitriol, Thyroxines, Retinoic Acid
What is the effect of lipid soluble hormones?
Control of gene expression (requires hours)
How do water soluble hormones regulate gene expression?
Through proteins such as cAMP response element binding (CREB protein) (requires hours)
Example of water soluble hormones
Insulin, Glucagon, Catecholamines
Process of signal transduction by water soluble hormones
Receptor –> G protein –> enzyme –> Second messenger —> Protein Kinase
What is the purpose of protein Kinase?
Take a phosphorylated Protein using ATP –> ADP, then phosphorylate a protein
Example of dephosphorylated Proteins
Gene regulator proteins
Enzymes (rate limiting)
Which enzyme converts a phosphorylated protein to devephosphorylated?
Protein Phosphatase
What does Protein Phosphatase use?
H2O –> Pi
Which hormone turns on Protein kinase?
Glucagon, phosphorylates everything
Which hormone turns on Protein phosphatase?
Insulin, dephosphorylates everything
How are G proteins consider?
Trimeric proteins, conform by α β γ subunits
Why are G proteins called that way?
Because they bind to GTP
Which subunit of G protein binds to GTP and obteins energy?
α, converting GTP to GDP
How is the process of Trimeric G protein cycle?
- Inactive G protein (means α subunit with GDP)
- Active G protein (means α subunit with GTP)
- Splitting of subunits α- GTP and β-γ
- α subunit has two types (αs- stimulates, αi- inhibits)
- Either way αs stimulates Adenylate cyclase or αi inhibits adenylate cyclase
- α subunit returns to GDP and the cycle is started again
How many transmemebrane domains do G protein coupled receptors have?
7 transmembrane domains
What is the outside cell terminus of transmembrane domain?
NH3 (Amino gropu)
What is the inside cell terminus of transmembrane domain?
COO- (carboxyl group)
How do we know is a G protein cell receptor?
By the 7 transmembrane domains
Example of Gs receptors
Glucagon
Epinephrine
Vasopressin in Kidney (ADH)
Example of Gi receptors
Epinephrine α2
ACh M2
What is the result of Gs?
↑ cAMP (second messenger)
In G protein stimulation which is the first messenger?
Hormone
In G protein stimulation which is the second messenger?
cAMP
What is the effect of Gi?
↓ cAMP
Once cAMP is increased what happens?
+ stimulation of Protein kinase A
Which protein kinase is stimulated with cAMP pathway?
Protein Kinase A
What is the action of Protein Kinase A?
Phosphorylates (examples Serine and Treonin) Phosphorylates CREB
Once CREB is stimulated, what happens next?
Goes to the nucleus and stimulate gene production
Which kind of receptors does PIP2 system have?
G protein cell receptor
What binds to G protein receptor in PIP2 system?
Vasopressin vacular
Epinephrine α1
ACh muscarinic 1 or 3
In PIP2 system instead of Gs what is the stimulant protein?
Gq
What does Gq stimulates in PIP2 system?
Phospholypase C
What is the function of Phospholypase C?
Breaks into two second messengers PIP2 (portion of the membrane-becoming DAG) and IP3 (which goes inside the cell)
What is the intracellular effect of IP3?
Goes to ER and increases Ca2+
In PIP2 system how is protein kinase C activated?
By increased intracellular Ca2+ (by IP3 stimualtion) and with DAG stimulation
Which protein Kinase is activated in PIP2 system?
Protein Kinase C
What is the effect of Protein Kinase C?
Gene expression
Enzymes phosphorylated
What is the final effect of energy Gq protein?
Increase Ca2+
Which are the second messengers in PIP2 system?
DAG, IP2, Ca2+
Which is the substrate to produce Nitric Oxide (NO)?
Arginine
Enzyme that converts Arginine to Nitric Oxide?
Nitric Oxide Synthase
Where is the NO synthase primarily found?
In endothelium
What characteristics of NO allows it to cross membrane?
That is a Gas, lipid soluble
Do NO requires receptor?
No, because it crosses membrane as a gas
After crossing membrane what is the effect of Nitric Oxide?
Stimulates soluble Guanylate Cyclase (Heme containing group)
What is the effect of Guanylate cyclase?
Converts GTP to cGMP
What is stimualted by cGMP?
Protein kinase G
In NItric Oxide pathway which is the second messenger?
cGMP
What is the final effect of Protein Kinase G?
Relaxation of smooth muscle (vasodilation)
Drugs that work at the nitric oxide pathway
Nitroprusside
Nitroglycerine
Isosorbide dinitrate
Hydralazine
Which is the drug of choice in hypertensive emergencies?
Nitroprusside
What is the secondary effect of Nitroprusside?
The prusside portion causes cianide toxicity
What is recommended when administering Nitroprusside?
Never administering more than a day or two days
What is the primarily effect of Nitroglycerine and Isosorbide dinitrate?
↓ venous pressure (venodilate) → decrease preload, oxigen demand for contraction, decrease cardiac output
Primary NO release in large veins, no effect on arteries
When is isosobide dinitrate recommended?
As antianginal drug, to prevent myocardial infarction
Mechanism of action of hydralazine?
Works releasing NO in arteries, antihypertensive medication pregnanacy
Characteristics of Guanylate cyclase
1 transmembrane domain
Does Receptor Guanylate cyclase have G protein?
No
For what is Receptor Guanylate cyclase?
For atrial Natriuretic Factor (ANF)
Which is a endogenous Diuretic?
Atrial Natriuretic Factor
How does Atrial Natriuretic factor works?
Stimulates Receptor guanylate cyclase–> ↑cGMP –> ↑ Protein Kinase G –> Relaxation of smooth muscle (vasodilation)
Which smooth muscle are relaxated by the effect of Atrial Natriuretic factor?
Afferent Arterioles of kidney
What is the effect of Atrial Natriuretic Factor?
Diuretic, ↑ Diuresis of Na+
Which drug is a recombinant form of Atrial Natriuretic Factor?
Nesirittide
What kind of receptor does Insulin have?
Two separetly receptors that become a dimer
What is activated once insulin is bind to the receptor?
Tyrosine kinase activity (Protein kinase)
Which aminoacid is phosphorylated once insulin is bind to a receptor?
Tyrosine
Where can we find Tyrosine kinase?
Bind to the dimeric receptor of insulin
After Tyrosine kinase is activated in insulin receptor what happens next?
Autophosphorylation of receptor (which is Tyrosine Kinase itself) inside the cell
What is the effect of Tyrosine kinase after phosphorylation?
Insulin receptor substrate (IRS) binds receptor and is phosphorylated on tyrosine residues
After IRS are phsophorylated, what is the result?
SH2 domain proteins bind phosphotyrosine residues on IRS
Which is the final step of Tyrosine kinase activation by binding insulin to the receptor?
Protein phosphatase activation which leads to enzymes dephosphorylated
Which mechanism does insulin follow in order to produce gene expression in nucleus?
p21 ras G protein stimulation
PI-3 kinase (important)
Which is the most common affected gene in cancer?
ras protein —> too much work, cause growth of everything including cancer
Which enzyme is important for insulin translocation of GLUT-4 tom membrane?
PI-3 kinase
In which cells membrane is GLUT-4 found?
Adipose and Muscle
Example of Insulin Growth factors
Insulin, IGF, PDGF, EGF
Which is the main factor related to all types of growth?
Tyrosine Kinase
Which drug inhibits Tyrosine Kinase?
Imatinib
Gene affected in CML
t (9:22)
bcr-abl
What is bcr-abl?
A Tyrosine kinase
When do we do Glycogen synthesis?
When glucose is high, when insulin is present (Store Glucose)
Which is the enzyme that forms glycogen?
Glycogen synthase
When is Glycogen Active?
When it does not have any phosphate, when insulin is around
What is the effect of Glucagon to Glycogen synthase?
Phosphorylates it, making it less active
What is the effect of Glucagon to Glycogen?
Glycogenolysis (release Glucose)
When is Glycogenolysis done?
When Glucose is low, when glucagon is present
Which is the enzyme activated by glucagon in order to make glycogenolysis?
Glycogen Phosphorylase
Which protein mutation is related ti cancer?
p21 ras (ras)
Which cancers are related to ras mutation?
Colon, lung, breast, bladder tumors
Which is the numer 1 cancer killing?
Breast cancer
Which is the numer 2 cancer killing?
Lung cacer
Which is the numer 3 cancer killing?
Colon
What predisposes to bladder cancer?
Smokers, aniline dyes–> ethylenalonamide, chronic inflammation due to cystosomises
What is associated to ras protein?
GTP
Which Exotin cause ADP ribosylation?
Cholera Toxin
E. Coli
Pertusis Toxin
Which Toxins affect Gs α?
Cholera toxin
E. ColiToxin
Which toxins affect Gi α?
Perutssis toxin
Type of diarrhea caused by E. Coli
Watery diarrhea (Travelers diarrhea)
Type of diarrhea caused by Cholera toxin
Rise water stoles
How is the mechanism of watery diarrhea caused by E. Coli and cholera?
- Stimulation od Gs α protein with toxin (Increased cAMP)
- Activation of Protein Kinase A
- Phosphorylation of CFTR channels in epithelium cells
- Leads to Cl- excretion (salt) by CFTR channels to the intestinal lumen
- Dilution of Cl- in intestinal lumen with water causing watery diarrhea
Type of toxins produce by Bordetella pertusis, E. Coli, Vibrio Cholera
Exotoxins
Type of diarrhea caused by E. Coli and Vibrio Cholera
Secretory Diarrhea
Toxins of E. Coli
Heat labile of LT
What effect foes Cortisol have when binding to response elements?
It binds to the enhancer region of the phosphoennolpyruvate
Carboxykinase (PEPCK) gene
How does Cortisol cause hyperglycemia?
By increasing the amount of PEPCK in the hepatocytes, Cortisol can increase the capacity for gluconeogenesis
