Glyceroneogenesis
Glyceroneogenesis is used when the concentrations of glucose in the cytosol are low, and typically uses pyruvate as the precursor, but can also use alanine, glutamine, or any substances from the TCA cycle.
[1] When an organism is deficient in glucose, from (for example) fasting or a low carbohydrate intake, glycerol 3-phosphate is generated by glyceroneogenesis instead.
When pyruvate or lactate is used as the precursor for glycerol 3-phosphate, glyceroneogenesis follows the same pathway as gluconeogenesis until it generates dihydroxyacetone phosphate.
After the production of phosphoenolpyruvate, gluconeogenesis will continue until dihydroxyacetone phosphate is generated, which produces 2-phosphoglycerate, 3-phosphoglycerate, 1,3-bisphosphoglycerate and glyceraldehyde 3-phosphate as intermediates.
Glucocorticoids are steroid hormones involved in the reciprocal regulation of glyceroneogenesis in the liver and adipose tissues.
In adipose tissue, glyceroneogenesis restrains the release of free fatty acids (FFA) by re-esterifying them.
White adipose tissue stores energy in the form of triglycerides, which can be broken down to free fatty acids on demand.
[3] Brown adipose tissue stores free fatty acids rather than triglycerides, and is especially abundant in newborn and hibernating mammals.
Brown adipose tissue is involved in thermogenesis, and has a considerably higher glyceroneogenesis activity.
Glyceroneogenesis in brown adipose tissue contributes to thermogenesis, a process that generates heat in warm-blooded animals by delivering free fatty acids to the mitochondria.
When exposed to cold, a neurotransmitter hormone called norepinephrine suppresses the activity of PEPC-K and thus the glyceroneogenesis re-esterification, increasing the availability of free fatty acids within the cell.
[citation needed] This finding was unexpected because triglyceride synthesis in the liver was thought not to occur due to the amount of gluconeogenesis taking place[clarification needed], and because the liver was believed to have sufficient glycerol 3-phosphate collected from the bloodstream.
[3] It was subsequently found that the liver synthesizes more than half of the glycerol mammals need to regulate lipids.
Conversely, glyceroneogenesis is induced in the liver and suppressed in adipose tissues when the blood lipid level is low.
Conversely, in adipose tissue, down-regulated glyceroneogenesis may decrease de novo lipogenesis, increasing the export of free fatty acids to the bloodstream, leading to lipodystrophy.
Regulation of glyceroneogenesis is a therapeutic target of type 2 diabetes treatment, specifically inhibiting it in the liver and increasing it in adipose tissues.
To restrict the release of free fatty acids from adipose tissues, glyceroneogenesis must be increased so they are re-esterified.
