Figure Insulin stimulates conversion of dietary carbohydrates and proteins into fat. In individuals with untreated diabetes mellitus, acetyl-CoA from catabolism of carbohydrates and proteins is instead shunted to ketone body production, because of the lack of insulin. Biosynthesis of Membrane Phospholipids In Chapter 9 we introduced two major classes of membrane phospholipids: glycerophospholipids and sphingolipids. We noted that many different phospholipid species can be constructed by combining various fatty acids and polar head groups with the glycerol or sphingosine backbones see Figs.
Although the number of different end products of phospholipid biosynthesis is very large, all of these diverse products are synthesized according to a few basic patterns. We will describe the biosynthesis of selected membrane lipids to illustrate these patterns. In general, the assembly of phospholipids from simple precursors requires 1 synthesis of the backbone molecule glycerol or sphingosine ; 2 attachment of fatty acid s to the backbone, in ester or amide linkage; 3 addition of a hydrophilic head group, joined to the backbone through a phosphodiester linkage; and in some cases, 4 alteration or exchange of the head group to yield the fmal phospholipid product.
In eukaryotic cells, phospholipid synthesis occurs primarily at the surface of the smooth endoplasmic reticulum. Some newly synthesized phospholipids remain in that membrane, but most are destined for other cellular locations. The process by which water-insoluble phospholipids move from the site of their synthesis to the point of their eventual function is not fully understood, but we will conclude by discussing some mechanisms that have emerged in recent years.
The first steps of glycerophospholipid synthesis are shared with the pathway to triacylglycerols Fig. Commonly but not invariably, the fatty acid at C-1 is saturated and that at C-2 is unsaturated. A second route to phosphatidate is the phosphorylation of a diacylglycerol by a specific kinase.
The polar head group of glycerophospholipids is attached through a phosphodiester bond, in which each of two alcoholic hydroxyls one on the polar head group and one on C-3 of glycerol forms an ester with phosphoric acid Fig. In the biosynthetic process, one of the hydroxyls is first activated by attachment of a nucleotide, cytidine diphosphate CDP.
Cytidine monophosphate CMP is then displaced in a nucleophilic attack by the other hydroxyl Fig. The CDP is attached either to the diacylglycerol, forming in effect an activated phosphatidate, CDP-diacylglycerol strategy 1 , or to the hydroxyl of the head group strategy 2. The central importance of cytidine nucleotides in lipid biosynthesis was discovered by Eugene P. Kennedy in the early s. Figure The phospholipid head group is attached to a diacylglycerol by a phosphodiester bond, formed when phosphoric acid condenses with two alcohols, eliminating two molecules of H 2 O.
Figure Two general strategies for forming the phosphodiester bond of phospholipids. In both cases CDP supplies the phosphate group of the phosphodiester bond. Phospholipid Synthesis in E. The diacylglycerol is activated by condensation of phosphatidate with CTP to form CDP-diacylglycerol, with the elimination of pyrophosphate Fig. Displacement of CMP through nucleophilic attack by the hydroxyl group of serine or by the C-1 hydroxyl of glycerolphosphate yields phosphatidylserine or phosphatidylglycerolphosphate, respectively.
The latter is processed further by cleavage of the phosphate monoester with release of P i to yield phosphatidylglycerol. Phosphatidylserine and phosphatidylglycerol can both serve as precursors of other membrane lipids in bacteria Fig.
Decarboxylation of the serine moiety in phosphatidylserine by phosphatidylserine decarboxylase yields phosphatidylethanolamine. Figure Origin of the polar head groups of phospholipids in E.
Initially, a head group either serine or glycerolphosphate is attached via a CDP-diacylglycerol intermediate strategy 1. For phospholipids other than phosphatidylserine, the head group is further modified, as shown here.
In the enzyme names, PG represents phosphatidylglycerol, and PS, phosphatidylserine. Hormonal regulation[ edit ] Insulin is a peptide hormone that is critical for managing the body's metabolism. Insulin is released by the pancreas when blood sugar levels rise, and it has many effects that broadly promote the absorption and storage of sugars, including lipogenesis. Insulin stimulates lipogenesis primarily by activating two enzymatic pathways.
Malonyl-CoA provides the two-carbon building blocks that are used to create larger fatty acids. Insulin stimulation of lipogenesis also occurs through the promotion of glucose uptake by adipose tissue. It is involved in the process by limiting fat storage through inhibition of glucose intake and interfering with other adipose metabolic pathways. Growth hormones result in loss of fat but stimulates muscle gain.
The phosphatase removes the phosphate from pyruvate dehydrogenase activating it and allowing for conversion of pyruvate to acetyl-CoA. This mechanism leads to the increased rate of catalysis of this enzyme, so increases the levels of acetyl-CoA. Increased levels of acetyl-CoA will increase the flux through not only the fat synthesis pathway but also the citric acid cycle.
It leads to its dephosphorylation via activation of PP2A phosphatase whose activity results in the activation of the enzyme. Glucagon has an antagonistic effect and increases phosphorylation, deactivation, thereby inhibiting ACC and slowing fat synthesis.
This butyryl group is then transferred to the CYS-SH 8 as for the case of the activating acetyl group.
One of the many effects of insulin is to lower cAMP levels which leads to increased dephosphorylation through the enhanced activity of protein phosphatases such as PP In the glycerolphosphate and other pathways, the starting material is of defined stereochemistry and each of the enzymes catalysing the various steps in the process is distinctive and can have preferences for particular fatty acids as their coenzyme A esters and for particular fatty acid combinations in the partially acylated intermediates. The polar head group of glycerophospholipids is attached through a phosphodiester bond, in which each of two alcoholic hydroxyls one on the polar head group and one on C-3 of glycerol forms an ester with phosphoric acid Fig. Figure 6.
Once formed, glycerolphosphate is acylated at the C-1 sn-1 position by one of a family of glycerolphosphate acyltransferase GPAT enzymes that are expressed in either the mitochondria or in the endoplasmic reticulum, ER.
Like adipose tissue cells, lipid droplets have a major function in that they sense and respond rapidly to changes in systemic energy balance. Part 1 discusses their structure and compositions in animals, plants and other organisms.
ELOVL7 shows no elongation activity towards fatty acids longer than 20 carbons. D'Andrea, S.
Indeed, this process is energetically equal to glucose-stimulated insulin secretion GSIS. Figure prepared from original data in [ 65 ]. Seed storage oil mobilization. A similar reaction has been observed in seed oils. The process of fat digestion is begun in the stomach by acid-stable gastric or lingual lipases, the extent of which depending on species but may be important for efficient emulsification. Although they originate in the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites in a highly dynamic manner.
The free fatty acids released have a similar effect, though by a very different mechanism, via the receptor GPR
Lipid metabolism is associated with carbohydrate metabolism, as products of glucose such as acetyl CoA can be converted into lipids. The lipid biochemistry of eukaryotic algae. It is specific for monoacylglycerols and has no activity against di- or triacylglycerols.