Lipid Synthesis - Biochemistry

Because acetyl-CoA Carboxylase (ACC) is directly responsible for synthesis of malonyl-CoA, inhibiting it would be the most targeted approach. Inhibiting acyl-CoA dehydrogenase or pyruvate dehydrogenase would decrease available acetyl-CoA to ACC by inhibiting beta-oxidation and conversion of pyruvate to acetyl-CoA, but this would have a large impact on other biosynthetic pathways as well, due to the ubiquity of acetyl-CoA.

-hydroxybutyrate dehydrogenase catalyzes the interconversion of the ketone bodies acetoacetate and -hydroxybutyrate, which are transported out of liver cells into the blood to be used as fuel by the rest of the body, particularly during times of starvation. -hydroxybutyrate dehydrogenase’s only coenzyme is . As for the other answers: the pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA, the key connection between glycolysis and the citric acid cycle, and this process uses a number of co-factors, including , thiamine pyrophosphate, lipoamide (the protein-bound form of lipoic acid), and, of course, coenzyme A (to make acetyl-CoA). Pyruvate dehydrogenase uses and depending on the cell type.

The endogenous, not the exogenous, pathway, involves the transformation of VDLDs into LDLs. Meanwhile, the exogenous, not the endogenous, pathway, involves transforming chylomicrons into remnants. The apolipoprotein in plasma (transporting cholesterol to the liver) which is the major component of HDL is A1, not B100. Macrophages do indeed oxidize LDLs and transform themselves into the foam cells which indicate atherosclerosis. This is one of the reasons that LDL cholesterol levels can indicate atherosclerosis (which is associated with increased risk of heart attack or stroke).

Acyl-Carrier Protein (ACP) is a protein that is important to the generation of lipids. Specifically, it aids in the production of fatty acids. Furthermore, ACP is just one component of the Fatty Acid Synthase enzyme, which is devoted to the synthesis of fatty acids.

To begin the process, ACP is first activated by having an acetyl-CoA molecule attached to it. Next, a compound called malonyl-CoA is attached to the bound acetyl-CoA. Malonyl-CoA is a three carbon compound, but upon being added to the acetyl-CoA, the malonyl-CoA becomes decarboxylated. The importance of this is that by producing carbon dioxide as a product, this helps to greatly drive the reaction forward.

Keep in mind that there are other chemical transformations happening when these malonyl-CoA molecules are being "stitched" together. Every time a malonyl-CoA is added, the carbon chain becomes increased by two more carbons. This keeps happening until, finally, a fatty acid is generated.

Lecithin-cholesterol acyltransferase-LCAT adds a fatty acid to cholesterol, which can then be loaded onto high-density lipoproteins. Without the enzyme, cholesterol does not get to be transported by high density lipoproteins to the liver. Cholesterol then accumulates in tissue such as the eye and renal tissue. LCAT does impact cholesterol transport. Lipoprotein lipase is the enzyme that hydrolyzes fatty acids from triglycerides and cholesterol. Fatty acid synthase converts malonyl-CoA into palmitate. Acetyl-CoA carboxylase is the enzyme that incorporates acetyl-CoA into fatty acids.

Fatty acid desaturases are located on the endoplasmic reticulum and convert saturated fatty acids to unsaturated fatty acids by producing double bonds. The enzymes have a N-terminal cytochrome b5-like domain. Arachidonic acid is a highly unsaturated fatty acid.

Citrate crosses the mitochondrial matrix into the cytosol and is converted into acetyl-CoA and oxaloacetate by citrate lyase during fatty acid synthesis, as part of the citrate shuttle. The process requires hydrolysis of energy-rich ATP bonds.

The role of fatty acid synthase is to synthesize fatty acids,more specifically to convert acetyl-CoA, malonyl-CoA, and NADPH to palmitate (a fatty acid) and NADP. It is a multienzyme complex consisting of 7 components: acetyl CoA-ACP transacetylase, malonyl-CoA-ACP transacetylase, Beta-ketoacyl synthase, Beta-ketoacyl reductase, Beta-hydroxyacyl dehydratase, enoyl reductase, thioesterase.

Beta-oxidation is the process by which fatty acid molecules are broken down in the mitochondria to generate acetyl-CoA, which then enters the Krebs cycle. Fatty acids are not aromatic (they do not have aromatic rings), rather they are organized in straight chains of hydrocarbons and are therefore aliphatic. Carnitine transports long-chain acyl groups from fatty acids into the mitochondria (so that they can undergo beta-oxidation). Fatty acid synthesis, however, takes place in the cytosol.

The molecule which is repeatedly added to a growing fatty acid is malonyl-CoA. Malonyl-CoA is synthesized from acetyl-CoA (two carbons) and (one carbon), and, thus, contains three carbons. Of course, it is important to remember that the of malonyl-CoA leaves during the reaction with the acyl chain being synthesized.

Cholesterol is synthesized from acetyl-CoA. A cholesterol molecule contains 27 carbons and an acetyl-CoA molecule contains 2 carbons. Cholesterol is synthesized from a total of 18 acetyl-CoA molecules. These 18 molecules undergo reactions that yield a 30 carbon molecule and 6 carbon dioxide molecules (total of 36 carbons). The 30 carbon molecule loses 3 methyl groups and becomes the 27-carbon cholesterol molecule. Malonyl-CoA, acetoacetic acid, and pyruvate are not involved in this pathway.

Statins function to decrease the activity of HMG-CoA reductase, an important enzyme in the cholesterol synthesis pathway. This enzyme converts HMG-CoA to mevalonate. This step is the rate-limiting (and irreversible) step in this pathway. Statins inhibit this enzyme; therefore, statins prevent the production of mevalonate and cause an accumulation of HMG-CoA. The HMG-CoA can be converted into acetyl-CoA, which can now be used for many other processes.

HMG-CoA can be found in two locations: cytosol and mitochondria. In the cytosol, HMG-CoA participates in the production of cholesterol. In mitochondria, it participates in the production of ketone bodies. The question states that ketone bodies are produced; therefore, the researcher must be analyzing the mitochondria. Recall that mitochondria has two membranes: an inner and an outer membrane. Ribosomes in cytosol synthesize cytosolic proteins. The nucleus contains histones, which are proteins that facilitate packaging of DNA molecules. Degradative enzymes are found in organelles such as lysosomes and peroxisomes. These organelles clean the cell by removing unwanted cell debris.

During palmitate synthesis, malonyl-CoA molecules keep on being added to the fatty acid chain, seven malonyl CoA molecules total. Ketogenesis does not involve the synthesis of ; rather, NADH is oxidized to as -hydroxybutyrate is formed from acetoacetate. The cofactor produced by the pentose phosphate pathway is NADPH, whereas the -oxidation-mediated degradation of fatty acids requires and FAD. Palmitic acid is indeed the precursor of stearic acid, as well as of many other fatty acids.

Adipocytes stock mainly fatty acids, not glycerol; glycerol produced during triacylglycerol degradation is shuttled through the blood to the liver. Lipase does not digest chylomicrons, but rather triacylglycerol, producing glycerol and fatty acids. The lipids (fatty acids) in fatty tissue mostly originate in our diet, not in our liver. Mammals specifically require certain polyunsaturated fatty acids which they are unable to synthesize, like linoleate; these are known as the essential fatty acids. Chylomicrons are proteins which carry triacylglycerols, cholesterol, and other lipids, obtained by the diet, away from the intestine. Chylomicrons are created in the endoplasmic reticulum of small intestine cells i.e., enterocytes and exoctyosed into lymphatic capillaries.

The proper order for fatty acid synthesis is condensation, reduction, dehydration, and reduction once again. This creates an activated acyl group that has been lengthened by two carbons through this anabolic biosynthetic pathway.

The sources of glycerol-3 phosphate for triglyceride synthesis are glycerol in the liver, but not the adipose tissue (adipose tissue does not have glycerol kinase) and from the conversion of dihydroxyacetone phosphate (obtained in glycolysis) to glycerol-3 phosphatase in liver and adipose tissue. Triglycerides are one of the most important forms of storage of lipids in the body.

Triglycerides are the major form of storing dietary lipids in the body.Triglycerides are composed of three fatty acids and a glycerol molecule. In glycerophospholipids the third fatty acid of a triglyceride particle is replaced by a phosphate group and a choline or inositol group. Choline groups are ammonium salt groups in neurotransmitters or phospholipids on cell membranes. Inositol groups are found in second messengers. Glycerophospholipids are part of the cellular membrane and are sources of second messengers such as diacylglycerol and inositol-3-phosphate.

Cholesterol ester transfer protein's role in lipid metabolism involves transferring cholesterol esters or triglycerides between different types of lipoproteins in the blood. It is not part of the lipoprotein particle and is not a receptor but, rather, a protein in the blood. Cholesterol and triglycerides are carried in the blood by lipoproteins, which depending on the amount of protein contained are: chylomicrons, very low density proteins, low-density proteins, intermediate density lipoproteins and high density lipoproteins.