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CONTENTS Intro: Hyperammonemia is a serial killer Clinical presentation & diagnosis Causes Investigation & monitoring Management [1] Neurocritical care of hyperammonemia [2] Reduced enteral ammonia absorption [3] Basic nutritional manipulations [4] Discontinue potentially offensive medications [5] Consider treatment for infectious etiologies [6] Consider zinc supplementation [7] Consider carnitine supplementation [8] Consider additional vitamins [9] Consider L-arginine administration [10] Support renal clearance & consider CRRT [11] Sodium phenylacetate plus sodium benzoate (Ammonul) hyperammonemia is a serial killer hyperammonemia is a serial killer Nonhepatic hyperammonemia behaves like a serial killer

The mammalian nervous system, especially for neurons, depends heavily on autophagy to clear large amounts of insoluble protein aggregates to maintain protein homeostasis (73)

Research applications: Widely cited in tissue-repair, gastrointestinal, and musculoskeletal research literature

In proof-of-concept studies, NNMT inhibitors (NNMTis) have demonstrated promise as potential treatments for obesity and obesity-related metabolic comorbidities (e.g., T2D, fatty liver) 8,9,13