in forming an active form of ghrelin, which can then be secreted into the bloodstream. Ghrelin O-acyltransferase also plays a role in preventing hypoglycemia when there is prolonged negative energy balance in the body. GOAT plays a crucial role in the ability to maintain glucose levels during fasting and starvation. Additionally, the enzyme has a key role in modulating the secretion and sensitivity of insulin. These interactions are used in regulating glucose metabolism in the body. Regulation Ghrelin O-acyltransferase is highly regulated by energy balance and is upregulated when energy is restricted, such as when fasting. Additionally ghrelin O-acyl transferase function is activated by high bioavailability of lipids and fatty foods. The expression of this enzyme is also regulated by several different growth and appetite related hormones. For example, research has shown that the hormone leptin increases ghrelin O-acyl transferase mRNA levels, and therefore enzyme expression. Inhibition Ghrelin O-acyl transferase inhibitors often result in increased insulin secretion, potentially preventing diabetes and obesity. However, the lack of mechanistic information about the active site of the enzyme prevents rational design of inhibitor molecules. Nonetheless, there have been two general classes of ghrelin O-acyl transferase inhibitors which have been described in scientific literature: substrate mimics and small molecules. In terms of substrate-memetic inhibitors, it has been determined that ghrelin O-acyl transferase is subject to end product inhibition, also known as feedback inhibition. As such, changing the ester linkage between the n-octanoyl group and ghrelin into an amide group decreases the potency of the enzyme. Replacing the acyl chain entirely with a more biologically stable product inhibits the enzyme through competitive binding with the active site of the enzyme. Many similar substrate mimics use chemical modification on the ghrelin molecule to prevent ghrelin O-acyl transferase from carrying out the acylation reaction that activates ghrelin. Other approaches in the category include altering functional group or amino acid stereochemistry to greatly decrease enzyme binding affinity between ghrelin O-acyl transferase and ghrelin. There have also been recent advances in small molecule, drug-like inhibition of the ghrelin O-acyl transferase enzyme. One study has shown that a class of triterpenoid related molecules has significant inhibitory activity towards the enzyme. These analyses suggest that there is an essential cystine residue in the active site of ghrelin O-acyl transferase that has a role in the enzyme’s catalytic function or inhibitor site binding. This class of inhibitors have been shown to alter