ENZYMES, GROWTH FACTORS, PROTEINS, AND RECEPTORS

Histidine decarboxylase

enzyme involved in synthesizing histamine from histidine

CYP2D6

drug-metabolizing enzyme that acts on prodrug codeine, metabolizing it into morphine

Thiopurine S-methyltransferase (TPMT)

enzyme that metabolizes and inactivates the active drug 6-mercaptopurine

Xanthine Oxidase (XO)

enzyme that can metabolize 6-Mercaptopurine

Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)

salvage pathway enzyme that activates 6-Mercaptopurine to form 6-Thioguanine Nucleotides (6-TGN)

Cytochrome P450 2C9 (CYP2C9)

enzyme that metabolizes S-warfarin, the more potent component of warfarin

Vitamin K Epoxide Reductase (VKOR)

enzyme whose inactivation mediates the action of warfarin, playing a role in the recycling of Vitamin K for the coagulation process

Phospholipase A2

enzyme that converts arachidonic acid in the cell membrane to free arachidonic acid in the presence of inflammatory stimuli

Cyclooxygenase (COX)

enzyme pathway that breaks down arachidonic acid, leading to the generation of various prostaglandins

COX-1

cyclooxygenase enzyme that produces gastroprotective prostaglandins, such as PGE2

Lipoxygenase

enzyme pathway for arachidonic acid breakdown that leads to the generation of leukotrienes

Serotonin Reuptake Transporters (SERT)

responsible for the reuptake of serotonin in nerve terminals

Monoamine Oxidase (MAO)

enzyme that breaks down serotonin

Aldehyde dehydrogenase

enzyme that breaks down serotonin

Cytochrome P450 (CYP) enzymes

a family of enzymes involved in the hepatic metabolism of SSRIs, as well as the biotransformation of many prescription drugs and warfarin

5-Lipoxygenase

enzyme whose inhibition, as by Zileuton, blocks the breakdown of arachidonic acid and the production of all leukotrienes

Renin

enzyme that catalyzes the conversion of angiotensinogen to angiotensin I, released in response to low blood pressure

Angiotensin Converting Enzyme (ACE)

enzyme found in the lungs that converts Angiotensin I to Angiotensin II

Aminopeptidase A (APA)

enzyme that degrades Angiotensin II to AT-III

ACE2

enzyme that degrades Angiotensin II to AT 1-7

Neprilysin

enzyme that metabolizes natriuretic proteins like ANP, BNP, and CNP, and also Adrenomedullin

Endothelin-converting enzyme

enzyme whose inhibition by Phosphoramidon decreases endothelin formation

Tissue kallikreins

enzymes that stimulate the production of Kallidin from low molecular weight kininogen

Plasma kallikrein

enzyme activated by blood coagulation factor XII, which activates the production of Bradykinin from high molecular weight kininogen

Kininases I and II

enzymes that inactivate Kallidin and Bradykinin into fragments

Lysozymes

enzymes found in tears, sweat, and saliva that disrupt the β1→4 linkages in the peptidoglycan backbone, contributing to non-specific immunity

Oxidase enzyme

enzyme produced by some Gram-negative rods, detectable by the oxidase test

Catalase enzyme

enzyme produced by some Gram-positive cocci, detectable by the catalase test through the liberation of oxygen from hydrogen peroxide (H2O2)

β-lactamases

detoxifying enzymes found in the periplasmic space of Gram-negative bacteria that inactivate certain antibiotics

Collagenase

enzyme from Clostridium perfringens that degrades collagen, promoting the spread of infection in tissue

Coagulase

enzyme from Staphylococcus aureus that works with blood factors to coagulate plasma, contributing to the formation of fibrin walls around staphylococcal lesions to protect them from phagocytosis

Hyaluronidases

enzymes from staphylococci, streptococci, and anaerobes that hydrolyze hyaluronic acid, aiding in their spread through tissues

Streptokinase/Fibrinolysin

enzymes from streptococci that dissolve coagulated plasma, aiding in rapid spread through tissues and used in treating acute myocardial infarction to dissolve fibrin clots

Hemolysin

a cytolysin enzyme that dissolves red blood cells

Leukocidin

a cytolysin enzyme that kills tissue cells or leukocytes

IgA1 proteases

enzymes that split and inactivate IgA activity, important in certain bacteria like Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae

H1 receptor

a G-protein coupled histamine receptor located in smooth muscle, endothelial cells, nerves, and respiratory epithelium, involved in allergic reactions

H2 receptor

a G-protein coupled histamine receptor located in gastric parietal cells that stimulates gastric acid secretion

H3 receptor

a G-protein coupled histamine receptor located in the Central Nervous System (CNS)

H4 receptor

a G-protein coupled histamine receptor located in immune cells, involved in allergic reactions

Muscarinic receptors

receptors targeted by first-generation antihistamines, contributing to adverse effects like dry mouth, urinary retention, and sinus tachycardia, also targeted to counter motion sickness

Serotonin receptors (5-HT receptors)

receptors scattered throughout the brain and body that mediate the effects of serotonin, affecting mood and condition

5-HT1A receptor

a serotonin receptor for which Buspirone acts as an agonist, used for anxiety and depression

5-HT1B/1D receptors

serotonin receptors for which Triptans and Ergotamine act as agonists, inducing vasoconstriction and inhibiting neurotransmitter release, used for migraine headaches

5-HT2 receptor

a serotonin receptor whose antagonists are associated with drugs like Clozapine and Olanzapine (schizophrenia), Methysergide (migraine prophylaxis), and Ketanserin (antihypertensive); Trazodone acts as an agonist for sleep-inducing effects

5-HT3 receptor

a serotonin receptor for which Ondansetron and Granisetron act as antagonists, serving as antiemetics

5-HT4 receptor

a serotonin receptor for which Cisapride acts as an agonist for cholinergic GI motility and decreasing cardiac toxicity; Tegaserod acts as an antagonist to inhibit peristalsis in irritable bowel disease

Alpha-adrenergic receptors

receptors affected by first-generation antihistamines, leading to adverse effects such as dizziness and postural hypotension

Cardiac Ion Channels (Potassium and Sodium channels)

channels affected by first-generation antihistamines, potentially leading to an increased QT interval and ventricular arrhythmias

Leukotriene LTD4 receptor

a receptor for leukotrienes whose antagonists (Montelukast, Pranlukast, Zafirlukast) inhibit LTD4 receptor binding, used for maintenance treatment of mild to moderate asthma

Angiotensin Receptor I (AT-1)

a G-protein coupled receptor that mediates the primary effects of Angiotensin II, causing strong vasoconstriction

AT-2 receptor

an angiotensin receptor that mediates anti-inflammatory, anti-proliferative, antihypertrophic, antifibrotic, proapoptotic, and vasodilatory effects, counterregulatory to AT-1 receptor binding

Mas receptor

a receptor through which AT 1-7 (a by-product of Angiotensin II degradation by ACE2) acts to mediate vasodilation, counteract proliferation, remodeling, and natriuresis

AT-4 receptors

receptors that bind AT-III and AT-IV (by-products of Angiotensin II degradation by Aminopeptidase A), influencing learning, memory, long-term potentiation, and glucose uptake

ET-A receptor

the predominant endothelin receptor for ET-1, with less affinity for ET-3, active in smooth muscles to mediate an initial transient vasodilation followed by sustained vasoconstriction; also involved in proliferation, fibrosis, and repair mechanisms

ET-B receptor

an endothelin receptor with equal affinity for ET-1 and ET-3, found in the vasculature, and capable of producing vasoconstriction after an initial vasodilation; also involved in proliferation, fibrosis, and repair mechanisms

NPY receptors (Y1, Y2, Y4, Y5)

G-protein coupled receptors for Neuropeptide Y, which have inhibitory effects on adenylyl cyclase

Y1, Y2, and Y5 receptors

Neuropeptide Y receptors that mediate cardiovascular NPY activity/effects and vasoconstrictive properties

Y4 receptor

Neuropeptide Y receptor that mediates Pancreatic polypeptide activity

Y5 receptor

Neuropeptide Y receptor that mediates orexigenic properties

V1a receptor

a vasopressin receptor that mediates vasoconstriction, targeted by synthetic agonists like Selepressin and Terlipressin

V1b receptor

a vasopressin receptor that mediates the release of ACTH by pituitary corticotrophs

V2 receptor

a vasopressin receptor that mediates increased water reabsorption, targeted by antagonists like Tolvaptan for hyponatremia

UII receptor

the receptor for Urotensin, whose antagonists include Urantide and Palosuran

B1 receptors (kinin)

kinin receptors that are more inducible in times of injury but are less ubiquitous than B2 receptors

B2 receptors (kinin)

kinin receptors that mediate the vasodilatory effects of kinins, including increased vascular permeability, pain stimulation, and smooth muscle contraction

Natriuretic Receptor (NPR) A

a receptor for Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP)

NPR B

a receptor for C-type Natriuretic Peptide (CNP)

NPR C

a receptor that binds all three natriuretic proteins (ANP, BNP, CNP)

VPAC1 and VPAC2 receptors

G protein-coupled receptors for Vasoactive Intestinal Peptide (VIP), found in the central nervous system, heart, blood vessels, lungs, gastrointestinal tract, urogenital tracts, skin, eyes, ovaries, thyroid gland, and other tissues

VPAC2 receptor

a Vasoactive Intestinal Peptide (VIP) receptor targeted by Vasomera for the treatment of heart failure and pulmonary hypertension

NTS1 receptor

a neurotensin receptor with the highest binding affinity and most widespread distribution

NTS2 receptor

a neurotensin receptor associated with disorders involving dopamine pathways, explored for use in schizophrenia, Parkinson’s disease, and drug abuse

NTS3 receptor

a neurotensin receptor that does not contribute to the actions of neurotensin

AM₁ and AM₂ receptors

adrenomedullin receptors found in vascular and smooth muscles, mediating its effects

Relaxin XRX Family of Receptors (RXFPR 1)

the receptor through which Relaxin acts

RXFP3

the receptor for Insulin Like 3 peptide

CRHR1 and CRHR2

G protein-coupled receptors for Urocortin, expressed in the central nervous system (specifically the hypothalamus), cardiovascular, digestive, and immune systems, kidneys, adrenals, and other tissues

NK1, NK2, and NK3 receptors

receptors that mediate the actions of Substance P, with NK1 having the highest affinity

NK1 receptor

a receptor for Substance P whose antagonists, such as Aprepritant, are used for the prevention of post-chemotherapy emesis

Oligosaccharide receptors

receptors on epithelial cells to which the pili of Neisseria gonorrhoeae specifically bind

Major Histocompatibility Complex (MHC) molecules

molecules that bind superantigens, stimulating large numbers of T-cells

T-cell receptors (TCR)

receptors on T-cells that bind superantigens, stimulating large numbers of T-cells to produce massive quantities of cytokines

CYP450 enzymes

a family of enzymes whose polymorphisms may significantly affect blood levels, altering response to many drugs, and which are involved in the biotransformation of over 75% of prescription drugs, including warfarin metabolism

VKORC1 (Vitamin K epoxide reductase complex subunit 1)

a gene/allele whose haplotypes are categorized into two groups, Group A and Group B, impacting the required warfarin dose

Klotho variant rs36217263

a genetic variant associated with poor response to cardioselective beta-blocker therapy among Filipinos, where deletion of at least one copy of allele A is linked to this poor response

Charantins

insulin-like properties found in Ampalaya (bitter gourd)

Chrysophanic Acid

an ingredient found in Akapulko that makes it effective against fungal and skin infections

Copper

an ingredient found in Bayabas, known for its antimicrobial property

Hyperforin

an active constituent of St. John’s Wort that acts as a ligand for the xenobiotic pregnane X receptor (PXR)

PXR (xenobiotic pregnane X receptor)

a nuclear receptor that regulates the expression of proteins that transcriptionally regulate CYP450 3A4

Histamine

an autacoid released from cells in response to various stimuli to elicit local responses, known as a mediator of allergic reactions and involved in physiological processes like immune responses, gastric acid secretion, and the sleep and wake cycle

Serotonin (5-hydroxytryptamine)

a natural neurotransmitter produced by serotonergic cells from tryptophan, affecting the regulation of mood and social behavior, appetite, digestion, sleep, memory, and sexual desire and function

P-glycoprotein (PgP)

a pump that removes drugs from cells, regulating MDR-1 and other drug transporters, whose expression can be increased by St. John's Wort

Arachidonic acid

the parent structure of most NSAIDs, a normal component of membranes that is converted to free arachidonic acid by phospholipase A2 in the presence of inflammatory stimuli, breaking down via lipoxygenase and cyclooxygenase pathways

Prostaglandins

potent proinflammatory autacoids derived from fatty acids, mediating cardinal signs of inflammation (redness, heat, swelling, pain), causing local vasodilation, stimulating the hypothalamus, sensitizing nerves to pain, initiating blood clotting, and producing protective mucus in the stomach

Thromboxane A2

a prostaglandin product generated via the cyclooxygenase pathway that is involved in platelet aggregation and vasoconstriction

Prostacyclin (PGI2)

a prostaglandin product generated via the cyclooxygenase pathway that is involved in vasodilation and the inhibition of platelet aggregation

Leukotrienes (LTB4, LTC4, LTD4, LTE4)

pro-inflammatory products generated via the lipoxygenase pathway of arachidonic acid breakdown, implicated in bronchoconstriction, vasodilation, increased cell permeability, increased mucus production, inflammatory cell infiltration, tissue edema, and smooth muscle hyperplasia/hypertrophy

N-acetyl-benzoquinoneimine (NAPQI)

a hepatotoxic metabolite of acetaminophen that accumulates at very large (toxic) doses due to the depletion of glutathione donors, leading to signs of toxicity such as renal tubular necrosis and liver necrosis