AMP

**1. Adenosine monophosphate (AMP) – the main USMLE meaning** - Structure: adenine + ribose + one phosphate. Formed from ATP → ADP → AMP by hydrolysis, or by adenylate kinase (2 ADP ⇌ ATP + AMP). - **cAMP**: made from ATP by adenylyl cyclase; degraded to 5'-AMP by phosphodiesterase (PDE). Caffeine/theophylline inhibit PDE (↑cAMP); sildenafil inhibits PDE5 (cGMP). cAMP activates protein kinase A (PKA). Gs-coupled receptors ↑cAMP (β1, β2, D1, H2, V2, glucagon, ACTH, TSH, FSH/LH, PTH, calcitonin, CRH, hCG, MSH); Gi-coupled receptors ↓cAMP (M2, α2, D2, H3, μ/δ/κ opioid). Cholera toxin (Gs, ADP-ribosylation → permanently on) and pertussis toxin (Gi → off) alter cAMP. Heat-labile E. coli toxin ↑cAMP; anthrax edema factor and Bordetella adenylate cyclase toxin also ↑cAMP. - **AMP-activated protein kinase (AMPK)**: activated by high AMP:ATP ratio (low energy state). Effects: ↑catabolism (glucose uptake, fatty acid oxidation, ↑GLUT4 translocation), ↓anabolism (inhibits acetyl-CoA carboxylase → ↓fatty acid synthesis, ↓HMG-CoA reductase). **Metformin** activates AMPK (and inhibits mitochondrial complex I and hepatic gluconeogenesis). - **Allosteric regulation**: AMP activates phosphofructokinase-1 (glycolysis) and glycogen phosphorylase (muscle); inhibits fructose-1,6-bisphosphatase (gluconeogenesis). - **Purine metabolism**: IMP → AMP (via adenylosuccinate, requires GTP; aspartate donates nitrogen) and IMP → GMP (requires ATP). AMP → IMP via AMP deaminase → inosine → hypoxanthine → xanthine → uric acid (xanthine oxidase; target of allopurinol/febuxostat). Adenosine deaminase (ADA) deficiency → ↑dATP → inhibits ribonucleotide reductase → ↓ lymphocytes → **AR SCID**. Myoadenylate deaminase deficiency causes exercise-induced myalgia. - Pharmacology: adenosine (given for SVT) acts on A1 receptors (Gi) → ↓cAMP, ↑K+ efflux in AV node. Methylxanthines antagonize adenosine receptors. - Mnemonic for purine synthesis drugs: mycophenolate/ribavirin inhibit IMP dehydrogenase (IMP → GMP); 6-MP/azathioprine inhibit de novo purine synthesis.

**2. Antimicrobial peptides (AMPs)** - Innate immune effectors (defensins, cathelicidin LL-37) that disrupt microbial membranes; produced by neutrophils, epithelial cells (Paneth cells in gut crypts). Defensin deficiency is associated with Crohn disease (NOD2 mutations → ↓α-defensin).

**3. Other uses** - "AMP" = ampicillin (aminopenicillin; covers Listeria, Enterococcus, some gram-negatives—"HELPSS"/"HHEELPSS" organisms; combine with sulbactam for β-lactamase coverage). - "Amp" = ampule/ampere/amplitude in non-board contexts.

**High-yield takeaway**: AMP = low-energy signal (↑AMP:ATP → AMPK ↑ → catabolism); cAMP is the second messenger broken down to AMP by phosphodiesterase.