BIOCHEMICAL COMPONENTS

HMG CoA reductase

What is the rate-limiting and regulatory enzyme for cholesterol synthesis that converts HMG CoA to Mevalonate?

What enzyme is selectively and competitively inhibited by statins?

What enzyme is upregulated by a reduction in hepatic cholesterol synthesis caused by statins?

What enzyme is inhibited by Bempedoic Acid at a site proximal to that of statins?

Cholesterol

What chemical is the end product of the synthesis pathway that begins with the condensation of Acetyl CoA?

Mevalonate

What is the intermediate precursor of cholesterol synthesis converted from HMG CoA by HMG CoA reductase?

Lipoproteins

What large macromolecular complex composed of lipids and proteins transports poorly soluble lipids through body fluid to and from tissues?

Apolipoproteins (ApoB-48, ApoB-100, ApoA-I, ApoA-II, ApoC-I, ApoC-II, ApoC-III, ApoE)

What proteins are associated or attached to lipoproteins, providing structural basis, acting as ligands for cell surface receptors, and activating enzymes important in lipoprotein metabolism?

ApoA-I and ApoA-II

What apolipoproteins are attached to the good cholesterol, HDL?

ApoB-48

What apolipoprotein is attached to chylomicrons, which are synthesized in the intestine?

ApoB-100

What apolipoprotein is attached to VLDL, IDL, or LDL, which are synthesized in the liver?

ApoE

What apolipoprotein, which chylomicron remnants acquire, allows interaction with the LDL receptor in the liver for clearance?

LDL receptor (LDLR)

What cell surface receptor in the liver interacts with chylomicron remnants (via ApoE) for clearance?

What receptor does ApoB-100 serve as the ligand for, facilitating LDL removal from circulation?

Lipoprotein lipase (LPL)

What enzyme hydrolyzes chylomicron remnants, stripping off triglycerides for storage and energy use in muscle and adipose tissue?

Hepatic lipase (HL9)

What enzyme hydrolyzes intermediate density lipoprotein (IDL) that is not removed by the liver, converting it to LDL?

Nascent HDL (or minimally lipidated good cholesterol)

What lipoprotein is produced by the liver and small intestine and begins the process of reverse cholesterol transport?

Free cholesterol

What molecule from macrophages and other peripheral cells is esterified by LCAT to be taken up by the liver in reverse cholesterol transport?

Lecithin-cholesterol acyltransferase (LCAT)

What enzyme esterifies free cholesterol from macrophages and other peripheral cells so it can be taken up by the liver in reverse cholesterol transport?

Scavenger receptor B1 (SR-B1)

What receptor facilitates the selective uptake of HDL by the liver?

Cholesteryl Ester Transfer Protein (CETP)

What protein transfers HDL cholesterol esters from HDL to VLDL and chylomicrons, which are then taken up by the liver for excretion?

HMG-CoA (3-Hydroxy-3-methylglutaryl-coenzyme A)

What compound is produced by the condensation of Acetyl CoA and converted to Mevalonate?

Isoprenoids

What molecules' synthesis is analogously impaired by statins?

Collagen

What protein's increase improves plaque stability due to statin's effects?

Matrix metalloproteinases (MMPs)

What enzymes' decrease improves plaque stability due to statin's effects?

Nitric oxide (NO)

What molecule's bioactivity is increased by statins, influencing endothelial function?

Endothelin

What molecule's level is decreased by statins, influencing endothelial function?

Apo A1

What apolipoprotein's transcription is regulated by statins, leading to an increase in HDL?

PPAR-ɑ (PPAR activators)

What nuclear transcription receptor is the ligand/target for fibric acid derivatives (fibrates)?

Intracellular lipase of adipose tissue

What enzyme is inhibited by Nicotinic acid (Niacin) via receptor-mediated signaling?

HCA2 (GPR109A)

What receptor's antagonism by Nicotinic acid (Niacin) inhibits intracellular lipase in adipose tissue?

Phospholipase C (PLC)

What enzyme breaks down phosphoinositides into IP3 and DAG in the smooth muscle contraction pathway initiated by Ach binding to the M3 receptor?

Myosin Light Chain Kinase (MLCK)

What enzyme is activated by the Calcium-calmodulin complex or calcium-troponin complex, leading to the phosphorylation of Myosin Light Chain in smooth muscle contraction?

Myosin Light Chain Phosphatase (MLCP)

What enzyme's activation, along with LTCC inhibition, is triggered by increased cGMP in the Nitrate pathway, leading to muscle relaxation?

Myosin Light Chain (MLC)

What protein component is dephosphorylated by MLCP, leading to decreased actin-myosin interaction and subsequent smooth muscle relaxation and vasodilation in the Nitrate pathway?

Acetyl CoA

What molecule's condensation begins the process of cholesterol synthesis, leading to HMG CoA?

L-Type Ca2+ channels (LTCC)

What calcium channels are inhibited by increased cGMP in the Nitrate pathway, leading to decreased intracellular Ca2+ levels and smooth muscle relaxation?

What voltage-gated channels mediate the entry of extracellular Ca2+ into smooth muscle and cardiac myocytes, and SA and AV nodal cells in response to electrical depolarization?

Calcium (Ca2+)

What ion's influx via L-Type channels is inhibited by CCBs, leading to muscle relaxation?

What ion's increased entry into the cell is caused by PK-A phosphorylation of L-Type calcium channels and sarcoplasmic reticulum sites upon noradrenaline binding to beta adrenoceptors?

What ion's influx causes depolarization in pacemaker cell action potential (Phase 0)?

What ion's influx is enhanced by K+ conductance and inhibited by cAMP, resulting in marked hyperpolarization of the AV node following Adenosine administration?

Sodium (Na+)

What ion's rapid influx causes depolarization in cardiac muscle action potential (Phase 0)?

What ion's slow influx causes pre-potential in pacemaker cell action potential (Phase 4)?

Potassium (K+)

What ion's movement out of the cell causes repolarization in both cardiac muscle (Phase 1, 3) and pacemaker cell action potential (Phase 3)?

What ion's channels are blocked by Class III antiarrhythmics (and quinidine/sotalol), leading to prolonged APD and ERP?

Glucocorticoid receptor (GR)

What intracellular receptor does Corticosteroid dock to, promoting the secretion of anti-inflammatory proteins (e.g., Annexin-1, SLPI, MKP-1) and suppressing pro-inflammatory secretions (e.g., Cytokines, Chemokines)?

Glucocorticoid response element (GRE) promoter region

What promoter region in the cell nucleus, when bound by corticosteroids, promotes the secretion of anti-inflammatory proteins?

NF-κB (nuclear factor-κB)

What proinflammatory nuclear factor is suppressed when Corticosteroid binds to its shared response element binding protein (CBP)?

Annexin-1, SLPI, MKP-1, IκB-α, GILZ

What anti-inflammatory proteins/molecules are promoted for secretion when corticosteroids bind to the GRE promoter region?

TSLP (Thymic Stromal Lymphopoietin), IL-25, and IL-33

What cytokines/molecules are released by airway epithelial cells/subepithelial mucosa upon activation stimulus (e.g., oxidant, virus, or allergen)?

IL-5 and IL-13

What interleukins are produced in the airway epithelium and subepithelial mucosa as part of the asthma inflammatory cascade, leading to accumulation of eosinophils, mast cells, and basophils?

IgE

What antibody's production is switched by naïve CD4+ T cells, resulting in the "arming" of mast cells and basophils in the asthma inflammatory cascade?

CBP (Cortisol Response Element Binding Protein)

What protein, shared with proinflammatory NF-κB, is bound by corticosteroid, leading to the suppression of various inflammatory mediators?

β2-adrenoceptors

What G-Protein Coupled Receptors (GPCRs) are widely distributed in the lungs (airway smooth muscle, epithelial cells, mast cells, etc.) and mediate the effects of beta2-agonists, such as bronchodilation?

Adenylyl cyclase (AC)

What enzyme, activated by beta2-receptor coupled to Gs proteins, converts ATP to cAMP, which then leads to smooth muscle relaxation?

cAMP (cyclic AMP)

What second messenger activates PK-A in the beta-adrenoceptor signaling pathway, leading to increased Ca2+ in cardiac muscle?

What second messenger's breakdown is inhibited by Methylxanthines like Theophylline, leading to bronchodilation?

PK-A (protein kinase A)

What enzyme is activated by increased cAMP and phosphorylates L-Type calcium channels and sarcoplasmic reticulum sites, leading to increased intracellular calcium entry and enhanced release in the cardiac muscle?

PDE (Phosphodiesterase enzyme)

What enzyme breaks down cAMP and is inhibited by Methylxanthines like Theophylline?

MLCK (Myosin Light-Chain Kinase)

What enzyme's inactivation by beta2-agonists leads to airway smooth muscle relaxation, providing relief in asthma?

ROCK (Rho kinases)

What intracellular molecule, needed for smooth muscle contraction, is mediated by the beta2-agonist pathway?

Na+/H+ exchanger

What pathway is activated by the beta2-agonist pathway, leading to hypokalemia?

mu and kappa opioid receptors

What opioid receptors are agonized by Codeine and other opiate derivatives, suppressing the medullary cough center?

What opioid receptors are agonized by Morphine, leading to the inhibition of the cough reflex?

delta receptors

What opioid receptors are primarily responsible for the analgesic effect of Morphine?

G proteins

What receptors are coupled to µ and κ opioid receptors, whose inhibition of neurotransmitter release leads to the inhibition of the cough reflex by Morphine?

Voltage-gated calcium channels

What channels are bound presynaptically by Pregabalin, inhibiting excitatory neurotransmitters, resulting in its antiseizure and antinociceptive effects?

GABA pathways

What neural pathways are inhibited by Gabapentin, resulting in its antitussive effects?

alpha-adrenoceptors

What receptors are activated by sympathomimetic amines (decongestants), causing vasoconstriction?

What receptors are found in the medulla of the brain and are centrally activated by alpha2 agonists, inhibiting adrenergic outflow and decreasing BP?

alpha1-receptors

What receptors are blocked by alpha1-blockers (e.g., Prazosin, Terazosin), leading to vasodilation and decreased total peripheral resistance?

Angiotensin-converting enzyme (ACE)

What enzyme converts angiotensin I to the potent vasoconstrictor angiotensin II and is responsible for the breakdown of bradykinin?

Angiotensin II (AngII)

What potent vasoconstrictor is formed by ACE converting angiotensin I?

What compound's action on AT1 receptors in the kidney is inhibited by ARBs (e.g., Losartan)?

What compound causes vasoconstriction and is blocked by RAA inhibitors?

Renin

What enzyme converts angiotensinogen (from the liver) to angiotensin I and is secreted by the juxtaglomerular apparatus of the kidney?

What enzyme's binding to the receptor on angiotensinogen is blocked by Direct Renin Inhibitors (e.g., Aliskiren), inhibiting the conversion of angiotensinogen to angiotensin I?

Bradykinin and Substance P

What compounds' production is enhanced by ACE inhibitors, leading to the side effects of dry cough and angioedema?

Aldosterone

What molecule causes sodium retention, leading to increased blood volume, which is blocked by RAA inhibitors?

Angiotensin II Type 1 (AT1) receptors

What receptor, found in the kidney, does Angiotensin II act upon, and is antagonized by ARBs?

What receptors' blockade by ARBs leads to arteriolar vasodilation?

Angiotensin II Type 2 (AT2) receptors

What receptor is blocked by ACE inhibitors?

Renin-angiotensin-aldosterone system (RAAS)

What system's overall effect is blocked by Direct Renin Inhibitors?

Natriuretic peptides

What molecules are degraded by Neprilysin, whose inhibition potentiates natriuresis?

Neprilysin

What enzyme degrades natriuretic peptides, and is inhibited by Sacubitril (a prodrug)?

Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP)

What natriuretic peptides' breakdown is reduced by Sacubitril (neprilysin inhibitor)?

BNP (Brain-type natriuretic peptide)

What biomarker, when equal to or above 35 pg/mL, along with NT-proBNP, suggests heart failure and prompts progression to echocardiography?

NT-proBNP (N-terminal pro-brain-type natriuretic peptide)

What biomarker, when equal to or above 125 pg/mL, along with BNP, suggests heart failure and prompts progression to echocardiography?

beta-1 receptors

What receptors are competitively blocked by carvedilol, reducing heart rate and blood pressure?

Nitric oxide (NO)

What molecule is released by Isosorbide dinitrate and Nitroprusside, activating guanylyl cyclase?

What molecule is likely increased in synthesis by Hydralazine?

Guanylyl cyclase

What enzyme is activated by Nitric Oxide (NO) released by Isosorbide dinitrate and Nitroprusside?

What enzyme is activated by the synthetic peptide Nesiritide (a form of BNP), increasing cGMP in smooth muscle cells?

Sodium/Potassium-ATPase (Na+/K+-ATPase or sodium pump)

What membrane-bound transporter is inhibited by Digoxin, resulting in reduced Ca2+ expulsion and increased Ca2+ stored in the sarcoplasmic reticulum?

What pump is inhibited by Istaroxime, increasing contractility?

beta1-selective agonist

What type of agonist is Dobutamine, increasing cAMP synthesis, cardiac contractility, and output?

cAMP (cyclic adenosine monophosphate)

What second messenger's synthesis is increased by Dobutamine (beta1-selective agonist)?

What second messenger's breakdown is inhibited by Milrinone (bipyridine), increasing contractility via increased inward calcium flux?

Dopamine receptor agonist

What type of agonist is Dopamine (at lower doses)?