Urea cycle biochemistry

\( \newcommand\)). (It is important to note that only ammonia can cross cellular membranes.)The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis). Transport of nitrogen via amino acids The amino acid pool is continually in flux and can be influenced by both dietary protein consumption as well as normal protein turnover within the tissues. Given that the major site of nitrogen disposal is the liver, a mechanism for transport of excess amino acid nitrogen from the peripheral tissues to the liver is in place. Both alanine and glutamine play an essential role as nontoxic carriers of ammonia from peripheral tissues to the liver (figures 5.12 and 5.13). To generate alanine and glutamine for transport, amino acids can undergo transamination reactions. Figure 5.12: Transamination reaction. Transamination: The movement of nitrogen Amino transferases are a family of enzymes (which require pyridoxal phosphate; PLP) as a cofactor to help transfer nitrogen from amino acids on to keto-acid backbones. These enzymes do not free ammonia, but will transfer nitrogen from an amino group to a keto-group in an exchange or transferase reaction. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are common and clinically relevant transferases. AST will preferentially accept aspartate and transaminate it in a reaction with...

• Describe the effect of insulin, glucagon, epinephrine, and cortisol on metabolic processes in the liver, adipose, and skeletal muscle and how these hormones function to regulate blood glucose homeostasis. • Determine the fuels utilized by the liver, red blood cells, adipose, skeletal muscle in the fed and fasted states and determine the pathway(s) providing this substrate. • Differentiate between insulin sensitive and insulin insensitive tissues; identify the GLUT transporters common to specific tissues and their clinical relevance. • Review the signaling mechanisms used by insulin, glucagon, cortisol, and epinephrine. One of the fundamental homeostatic responses is the regulation of blood glucose by alterations in flux through metabolic pathways. This regulation includes both dietary intake of fuels, tissue uptake and oxidation of fuels, and storage and release of fuels under necessary conditions. Most of these processes are controlled hormonally by insulin, glucagon, cortisol, and epinephrine. Ultimately, these pathways ensure that both ATP levels are sufficient for an organism to sustain cellular activities and that blood glucose is maintained in a narrow window. Both processes are balanced without exhausting either fuel and energy resources. Glucose homeostasis is fundamental to the human body and regulated primarily by the levels of fourmajor hormones: • Insulin, • Glucagon, • Cortisol, and • Epinephrine. The ratios of these hormones in circulation will dictate the ...

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Urea Cycle The urea cycle is a sequence of six enzymatic and two transport steps necessary to metabolize and excrete the nitrogen generated by the breakdown of amino acids in protein and other nitrogen-containing molecules. From: Neurology and Clinical Neuroscience, 2007 Related terms: • Citrulline • Amino Acids • Glutamine • Arginine • Brain • Seizure • Stroke Ryan Michael McAdams, Christopher Michael Traudt, in Avery's Diseases of the Newborn (Tenth Edition), 2018 Urea Cycle Disorders Urea cycle disorders are autosomal recessive disorders with the exception of ornithine transcarbamylase deficiency, which is X-linked. Neonates with absent urea cycle enzyme activity typically present with hyperammonemic coma within the first week after birth. Outcomes can be severe, with high morbidity and mortality approaching 50% ( Batshaw and Monahan, 1987). Acute hyperammonemia selectively affects the white matter of the brain and initially may be seen as reversible changes involving the deep sulci of the insular and perirolandic region watershed territories. Hypoperfusion associated with urea cycle disorders may play a role in causing brain inury. Urea cycle disorders (UCDs) represent a group of rare inherited metabolic disorders resulting from a partial or complete deficiency of one of the urea cycle components, thereby resulting in accumulation of ammonia, as well as other nitrogenous products, including glutamine and alanine. It is important to maintain normal ammonia, as hyperammo...