The intracellular levels of malonyl-CoA represent a balance between its synthesis from acetyl-CoA by ACC and its utilization in fatty acid synthesis by FAS as well as by its degradation to acetyl-CoA via the action of malonyl-CoA decarboxylase (MCD). One particular type of choline plasmalogen (1-O-1′-enyl-2-acetyl-sn-glycero-3-phosphocholine) has been identified as an extremely powerful biological mediator, capable of inducing cellular responses at concentrations as low as 10–11M. 1984 May-Jun;79(3):268-73. doi: 10.1007/BF01908026. PAF functions as a mediator of hypersensitivity, acute inflammatory reactions and anaphylactic shock. Arachindonate is a precursor for the eicosanoids (the prostaglandins, thromboxanes, and leukotrienes). Phosphorylation of ACC1 at three serine residues (S79, S1200, and S1215) by AMPK leads to inhibition of the enzyme. They are a major component of membranes. There are three major pathways for the synthesis of triglycerides referred to as the glycerol-3-phosphate (G3P) pathway, the dihydroxyacetone phosphate (DHAP) pathway, and the monoacylglycerol pathway. The three fatty acids may or may not be identical. Uptake and degradation of triglycerides by lysosomes isolated from rat heart. As indicated above, ACC represents the rate-limiting reaction of de novo fatty acid synthesis and humans express two forms of the enzyme identified as ACC1 and ACC2. Sphingadienes are long chain sphingoid bases that contain an additional carbon-carbon double bond in the long-chain acyl moiety when compared to sphingosine. DeGrado TR, Holden JE, Ng CK, Raffel DM, Gatley SJ. Expression of the ChREBP gene is induced in the liver in response to increased glucose uptake. Both ACC1 and ACC2 contain at least eight sites that undergo phosphorylation. Translation of the isoform 2 protein initiates at a downstream start codon relative to isoform 1. The role of the mitochondrial malic enzymes is principally to provide the cell with an alternate source of pyruvate under conditions where glycolytic flux in reduced. The original ChREBP is now referred to as ChREBP-α and the novel alternative splice form is called ChREBP-β. are neutral fats. The fatty acids incorporated into TAGs are all activated to acyl-CoAs through the action of various acyl-CoA synthetases. There are 10 isozymes that are in the secretory pathway and these PLA2 isozymes are abbreviated sPLA2. This microsomal enzyme is regulated by phosphorylation (inactiycation)-dephosphorylation (activation) coupled to the beta-receptor--adenyl cyclase--protein kinase system. The binding of MLX to ChREBP occurs within a domain located in the C-terminal portion of ChREBP. The primary fatty acid synthesized by FAS is palmitic acid (palmitate). The desaturation of fatty acids occurs in the ER membranes as well. In humans the major enzyme responsible for the synthesis of CDP-diacylglycerol used for PI synthesis is likely to be the CDS1 encoded enzyme. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/, In the mammalian myocardium, an active triglyceride synthesis pathway is operating, (re)esterifying activated fatty acids from endogenous or exogenous sources, with the glycolytically derived three-carbon intermediates dihydroxyacetone-phosphate and glycerol-3-phosphate by the so-called Kennedy pathway. Insulin stimulates ACC and FAS synthesis, whereas, starvation leads to decreased synthesis of these enzymes. The synthesis of CDP-diacylglycerol is catalyzed by at least three enzymes that includes CDP-diacylglycerol synthase 1 and CDP-diacylglycerol synthase 2, which are encoded by the CDS1 and CDS2 genes, respectively. The second major pathway for PE synthesis occurs in the inner mitochondrial membrane and involves the decarboxylation of PS. Outside of the context of phospholipid remodeling PLA2 is an important enzyme, whose activity is responsible for the release of polyunsaturated fatty acids (PUFAs) such as arachidonic acid from the C2 (sn-2) position of membrane phospholipids. Epub 2007 Mar 15. The fatty acids present in TGs are predominantly saturated. USA.gov. The kinases PKA and AMPK both phosphorylate ChREBP rendering it inactive as a transcriptional activator. The reduced ACC2 activity, resulting in reduced levels of malonyl-CoA, is associated with increased fatty acid delivery to the mitochondria for oxidation which promotes exercise capacity. The seven enzymes of triglyceride synthesis are membrane bound and located at the sarcoplasmic reticulum. Adipose tissue contains hormone-sensitive lipase (HSL), that is activated by PKA-dependent phosphorylation leading to increased fatty acid release to the blood.  |  Also, linoleic acid is a constituent of epidermal cell sphingolipids that function as the skins’ water permeability barrier. The glycerol produced during the lipolysis of triglycerides a. is a waste product that is excreted from cells b. is stored within the cell for future synthesis of tryglycerides c. can be used as either a source of energy or for gluconeogenesis Correct. The remodeling of acyl groups in phospholipids is the result of the action of enzymes of the phospholipase A1 (PLA1) and phospholipase A2 (PLA2) families. There are exogenous (chylomicrons) and endogenous (pre-β-lipoproteins) triglycerides. The malate can then be decarboxylated to pyruvate via mitochondrial malic enzyme. The PAF hydrolyzing PLA2 isozymes are Ca2+-independent like the iPLA2 family. Most phospholipids have a saturated fatty acid on C-1 and an unsaturated fatty acid on C-2 of the glycerol backbone. The interactions of lipin-1 with PPARα and PGC-1α leads to increased expression of fatty acid oxidizing genes such as carnitine palmitoyltransferase 1 (CPT-1: encoded by the CPT1A gene), acyl-CoA oxidases (peroxisomal fatty acid oxidation pathway), and medium-chain acyl-CoA dehydrogenase (MCAD: encoded by the ACADM gene). The MECR gene is located on chromosome 1p35.3 and is composed of 15 exons that generate nine alternatively spliced mRNAs that collectively encode five distinct protein isoforms. Cytoplasmic fatty acid elongation is essentially an extension of the normal fatty acid synthesis reaction. The ME1 gene is located on chromosome 6q14.2 and is composed of 14 exons that encode a protein of 572 amino acids. The presence of a neutral lipase, as distinct from lipoprotein lipase, in the rat heart was recently advocated. Once released, palmitate can then undergo separate elongation and/or unsaturation to yield other fatty acid molecules. The 1,2-diacylglycerols are derived from the action of enzymes of the phospholipid phosphatase family, such as that encoded by the LPIN1 gene, on phosphatidic acid. Like the sPLA2 enzymes, the cPLA2 enzymes are tightly regulated by Ca2+. The sphingadienes constitute a class of lipid that has been shown to exert cytotoxic effects on certain types of cancers through their ability to inhibit the activity of the AKT/PKB signaling pathway. If the acyl chains at the end hydroxyl groups (1 & 3) of glycerol are different, the center carbon becomes a chiral center and enantiomeric configurations must be recognized. The specific phosphatidylcholine with both C-1 and C-2 esterified with palmitic acid (16:0) is commonly identified as dipalmitoyllecithin. In addition, it has been shown that when expression of ChREBP is reduced the expression levels of glycerol 3-phosphate acyltransferases, GPAT (encoded by four distinct genes: GPAM, GPAT2, GPAT3, GPAT4) and Δ9-stearoyl-CoA desaturase (SCD) are also reduced. The fatty acids are then incorporated into triglycerides and exported from hepatocytes as very-low-density lipoproteins (see the Lipoproteins page for more details) and ultimately stored as triglycerides in adipose tissue. Insulin, on the other hand, has the opposite effect to glucagon and epinephrine leading to increased glycogen and triacylglyceride synthesis. Finally, a class of PLA2 enzymes, whose original member was identified as being involved in the hydrolysis and inactivation of platelet activating factor, PAF (see the section below), contains at least four members. The domain that is required for attachment and transfer of acetyl-CoA and malonyl-CoA (acyltransferase domain) is composed of amino acids 493–810. Fetal lung maturity can be determined by measuring the ratio of lecithin to sphingomyelin (L/S ratio) in the amniotic fluid. The OXSM gene is located on chromosome 3p24.2 and is composed of 3 exons that generate two alternatively spliced mRNAs. It is this role of fatty acids in eicosanoid synthesis that leads to poor growth, wound healing and dermatitis in persons on fat free diets. In humans, fat constitutes an important part of the diet, and in some countries... Triglycerides in animals and … However, the activated form of acetyl-CoA in fat synthesis exists temporarily bound to the enzyme complex as malonyl-CoA. Ninja Nerds,Join us in this video where we discuss the process of triglyceride synthesis and all of the associated enzymes involved. As well, MCD inhibition leads to reduced triacylglyceride content in lipid synthesizing tissues such as the liver. The major building block for the synthesis of TGs, in tissues other than adipose tissue, is glycerol. The resultant oxaloacetate is converted to malate by cytoplasmic malate dehydrogenase (encoded by the MDH1 gene). Adipose tissue lipoprotein lipase levels also are increased by insulin and decreased by starvation. …acids in the diet is triglycerides, generically called fats. ALA has sites of unsaturation at carbons 9, 12, and 15 and is the precursor fatty acid in the pathway of. Adipocytes can be considered the major cell types tasked with triglyceride synthesis as these are the primary fatty acid storage cells the body. Whenever a greater quantity of carbohydrates enters the body than can be used immediately for energy or can be stored in the form of glycogen, the excess is rapidly converted into triglycerides and stored in this form in the adipose tissue. The triglyceride also contains three long chains of carbon and hydrogen, each of which has two oxygen atoms connected to one end. However, the majority of fatty acid biosynthesis occurs in hepatocytes and adipocytes. In the second reaction a 3-ketoacyl-CoA reductase activity (also called 3-oxoacyl-CoA reductase) reduces the resulting 3-ketoacyl-CoA intermediate to a 3-hydroxyacyl-CoA. In fact there is not just a single PLA2 enzyme. The DHAP is then reduced to glycerol-3-phosphate via the action of the cytoplasmic form of glycerol-3-phosphate dehydrogenase (encoded by the GPD1 gene) as opposed to condensation with glyceraldehyde-3-phosphate via the gluconeogenic action of aldolase A. Clinical significance of the plasmalogen biosynthesis pathway is evidenced by the severe phenotypes associated with deficiencies in enzymes of the pathway. Molecules with phosphorylated inositol are termed polyphosphoinositides. If you are diabetic and your blood sugar (glucose) is out of control, your triglycerides may be very high. The ACSF3 gene is located on chromosome 16q24.3 and is composed of 18 exons that generate four alternatively spliced mRNAs that collectively encode two different precursor proteins of 576 amino acids (isoform 1) and 311 amino acids (isoform 2). Fat… The reduction reactions of elongation require NADPH as co-factor. The GPAT2 gene is located on chromosome 2q11.1 and is composed of 22 exons that encode a 795 amino acid protein. PP2Aδ dephosphorylates S196 resulting in translocation of ChREBP into the nucleus. An additional pathway for the synthesis of PC involves the trimethylation of PE using S-adenosylmethionine (SAM; or AdoMet) as methyl group donor. Choline plasmalogen is abundant in cardiac tissue. A search for potential additional regulatory factors revealed a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor which was identified as carbohydrate-responsive element-binding protein (ChREBP). ELOVL7 shows no elongation activity towards fatty acids longer than 20 carbons. J Physiol Pharmacol. Plasmalogens are glycerol ether phospholipids. Under conditions of low glucose the LID inhibits transcriptional transactivation by the GRACE domain. 2017 Feb;68(1):3-11. Mutations in the ACSF3 gene result in the disorder called combined malonic and methylmalonic aciduria (CMAMMA). Synthesis of fatty acids in the mitochondria plays a critical role in the assembly of the components of the oxidative phosphorylation machinery as well as playing a role in the processing of mitochondrial RNAs. These molecules are found in high concentration in mitochondrial membranes and as components of pulmonary surfactant. Protein Synthesis Fidelity in tRNA Aminoacylation; Initiation of Protein Synthesis; Elongation; Termination of Translation; Transcription and Translation; Eukaryotic Genes DNA and Genomes in Eukaryotes; Structure of Chromatin; Chromatin Replication; Reverse Transcription; Eukaryotic Gene Structure ; Eukaryotic Information Flow; Eukaryotic Transcription; RNA Processing; Eukaryotic Translation; The activity of D6D requires pyridoxal phosphate (PLP, derived from vitamin B6), Mg2+, and Zn2+ ions and its activity is, therefore, affected by nutritional status. Indeed, MCD is involved in regulating malonyl-CoA levels in multiple tissues. ChREBP was identified as a major glucose-responsive transcription factor and it is required for glucose-induced expression of L-PK and the lipogenic genes, ACC1 and FAS. Subsequent to the identification of the LPIN1 gene in the fld mouse, two additional related genes were identified. Genes whose patterns of expression are under the control of ChREBP activity include L-PK, ACC1 and FAS as indicated above. The AGPAT2 gene is located on chromosome 9q34.3 and is composed of 6 exons that generate two alternatively spliced mRNAs encoding two different isoforms of the enzyme. Schoonderwoerd K, van der Kraaij T, Hülsmann WC, Stam H. Mol Cell Biochem. The regulation and actions of SREBP are discussed in the Cholesterol Metabolism page. 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-1. Humans express two major isoforms of ACC. Malonyl-ACP is successively elongated in the next series of reactions that begins through the action of 3-oxoacyl-ACP synthase that is encoded by the OXSM gene. Although ACC2 does polymerize in response to citrate, the extent of oligomerization does not appear to be as great as for ACC1, which is presumed to be due to its mitochondrial association. The GNPAT enzyme adds a fatty acyl group to the sn-1 position of DHAP. COVID-19 is an emerging, rapidly evolving situation. The MCAT gene is located on chromosome 22q13.2 and is composed of 4 exons that generate two alternatively spliced mRNAs encoding two distinct precursor proteins. Initiation of mitochondrial fatty acid synthesis involves the use of malonic acid. When hypothalamic MCD levels are experimentally increased in laboratory animals there is a dramatic increase in food intake, weight gain, and ultimately results in obesity. The 3-ketoacyl-CoA reductase activity of mammalian fatty acid elongation is associated with the enzyme hydroxysteroid 17-β dehydrogenase 12 encoded by the HSD17B12 gene. However, under conditions of insulin stimulation of the liver, glycolysis is highly active as a means to drive the excess glucose carbons into fatty acid synthesis. Genes encoding glucokinase (GK) and liver pyruvate kinase (L-PK) of glycolysis and ATP-citrate lyase (ACLY), ACC1, and FAS of lipogenesis are regulated by modulation of their transcription rates. With respect to fatty acid metabolism this yields dephosphorylated and inactive hormone sensitive lipase. Deficiencies in both GNPAT and AGPS result in the peroxisomal disorders of the rhizomelic chondrodysplasia punctata (RCDP) family. They are used as an energy source by cells or as building blocks of complex lipids like phospholipids. Recent evidence has demonstrated that the ChREBP gene is a direct target of LXRs and that glucose itself can bind and activate LXRs. A significant cause of death in premature infants and, on occasion, in full term infants is respiratory distress syndrome (RDS) or hyaline membrane disease. FEBS Lett. ACC2 was originally discovered in rat heart but is also expressed in liver and skeletal muscle. An additional family of two PLA2 isozymes that are Ca2+-independent for activity are identified as iPLA2. Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart. Conversely, inactivation of the MCD gene in mice protects the animals from high-fat diet-induced insulin resistance. Intracellular triglycerides occur as free floating cytosolic droplets, membrane-bound particles and lipid-filled lysosomes. Under these conditions the mitochondrial 2-carbon acetyl units can be stored as fat for future energy demands or diverted into cholesterol biosynthesis. They are an integral part of all complex lipids (cholesterol esters, triglycerides, and phospholipids) and are present in the body in the form of the so-called free fatty acids (SMK), unbound for other lipids. It has been acknowledged that the bulk of the intracellular neutral lipase represents the precursor of vascular lipoprotein lipase. The active FAS enzyme exists as a head-to-tail homodimer. The third enzyme that can synthesize CDP-diacylglycerol is a bifunctional enzyme that is also responsible for the condensation of a CDP-diacylglycerol with myo-inositol forming a PI. Fatty acid synthase is encoded by the FASN gene which is located on chromosome 17q25.3 and is composed of 43 exons that encode a protein of 2511 amino acids. ChREBP interacts with another bHLH protein identified as MAX-like protein X (MLX). The ELOVL4 encoded enzyme preferentially elongates very long-chain saturated fatty acids such as lignoceric (C24:0) and cerotic (C26:0) acids. This second PC synthesis pathway only occurs to a significant degree in hepatocytes and is catalyzed by phosphatidylethanolamine N-methyltransferase which is encoded by the PEMT gene. The first enzyme in the glycerol-3-phosphate pathway, glycerol-3-phosphate acyltransferase, is proposed to be rate limiting for triglyceride formation. This insulin-mediated effect has not been observed in hepatocytes or adipose tissues cells. The glucose sensing domain (GSM) is actually composed of two distinct sub-domains identified as the low-glucose inhibitory domain (LID) and the glucose-responsive activation conserved element (GRACE). The glycerol-3-phosphate pathway of triglyceride synthesis is referred to as the Kennedy pathway after Eugene Kennedy who first worked out the pathway of triglyceride synthesis and published his results in 1960. ATP-citrate lyase is encoded by the ACLY gene which is located on chromosome 17q21.2 and is composed of 30 exons that generate four alternatively spliced mRNAs, each of which encodes a unique protein isoform. All of the reactions of fatty acid synthesis are carried out by the multiple enzymatic activities of FAS. Recently a newly discovered mechanism of regulated ChREBP activity involves the tissue-specific transcription of an alternatively spliced form of ChREBP. Significantly high triglycerides may also lead to inflammation in the body, most notably the pancreas, this causes a condition called pancreatitis. Learners should be able to explain how the properties of triglycerides relate to their functions in living organisms and how the properties of phospholipids relate to their functions in living organisms.  |  The HSD17B8 gene is located on chromosome 6p21.32 and is composed of 9 exons that encode a 261 amino acid protein. The SCD enzyme is encoded by the SCD gene (also known as FADS5) that is located on chromosome 10q24.31 and is composed of 6 exons that generate at least two mRNAs that differ by alternative polyadenylation signal sequence utilization. Palmitate is then released from the enzyme via the thioesterase activity of FAS (contained in a domain composed of amino acids 2242–2488). Phosphatidylglycerols are also the precursors for the synthesis of the diphosphatidylglycerols (DPG) which are more commonly called the cardiolipins. Following adipose tissue activation of ChREBP-β expression, both ChREBP-α and ChREBP-β work in concert to dramatically alter lipogenic gene expression. This inhibition is reversed by glucose or a glucose metabolite. As the level of glucose rises the extent of ACC2 hydroxylation increases and the level of malonyl-CoA rises resulting in inhibition of fatty acid oxidation. Intestinal monoacylglycerides (MAG), derived from the hydrolysis of dietary fats, can also serve as substrates for the synthesis of triglycerides (TAGs) which can then be incorporated into chylomicrons. Phospholipids are synthesized by esterification of an alcohol to the phosphate of phosphatidic acid (1,2-diacylglycerol 3-phosphate). These secretory enzymes are low molecular weight proteins that are Ca2+-dependent and are involved in numerous processes including modification of eicosanoid generation, host defense, and inflammation. The D5D enzyme is encoded by the FADS1 gene located on chromosome 11q12.2 and is composed of 13 exons that encode a 501 amino acid protein. The last step in mitochondrial fatty acid synthesis reduces the trans-2-enoyl-ACP to an acyl-ACP in an NADPH-dependent reaction catalyzed by mitochondrial trans-2-enoyl-CoA reductase encoded by the MECR gene. Cholesterol and other fats in your blood are needed for certain body processes. This occurs through activation of several cAMP-independent kinases. ChREBP does not bind to ChoREs as a typical homodimeric bHLH transcription factor. The synthesis of fatty acids from acetyl-CoA and malonyl-CoA is carried out by fatty acid synthase, FAS. The cytoplasmic acetyl-CoA that is required for fatty acid biosynthesis (and cholesterol biosynthesis) is initially generated in the mitochondria primarily from two sources, the pyruvate dehydrogenase (PDH) reaction and fatty acid oxidation, but is also derived from mitochondrial amino acid catabolism. These fatty acids must be acquired from the diet and are, therefore, referred to as essential fatty acids. The phosphate of phosphatidic acid is removed, by phosphatidic acid phosphatase (PAP1), to yield 1,2-diacylglycerols (DAG). In the nucleus PP2Aδ dephosphorylates T666 which allows ChREBP to bind to specific sequence elements (ChoRE) in target genes. Studies have shown that loss of PHD3 activity (in knock-out mice) results in a significant reduction in ACC2 activity. The ratio of saturated to monounsaturated fatty acids in membrane phospholipids is critical to normal cellular function and alterations in this ratio have been correlated with diabetes, obesity, cardiovascular disease, and cancer. Elongation involves condensation of fatty acyl-CoA groups with either acetyl-CoA or malonyl-CoA.  |  For more details on the PLA2 family of lipases visit the Bioactive Lipids page. However, in contrast to the effects of insulin and starvation on adipose tissue, their effects on heart lipoprotein lipase are just the inverse. Although an additional PC biosynthesis pathway is known that involves the addition of choline to CDP-activated 1,2-diacylglycerol, this pathway is not known to occur in human cells.. Other members of the family include phospholipid phosphatase 1 (encoded by the PLPP1 gene) and phospholipid phosphatase 3 (encoded by the PLPP3 gene). Oxidation of fats involves the reduction of FAD and NAD+. The pathway for fatty acid synthesis occurs in the cytoplasm, whereas, oxidation occurs in the mitochondria. The functions of lipin-1α and lipin-1β appear to be complimentary with respect to adipocyte differentiation. The blood is the carrier of triglycerides [contained within very low density lipoproteins (VLDL) and chylomicrons], fatty acids bound to albumin, amino acids, lactate, ketone bodies, and glucose. However, it is in the liver where the synthesis process is most active and where it has the greatest metabolic relevance. ACC1 is strictly cytosolic and is enriched in liver, adipose tissue, and lactating mammary tissue. A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from tri- and glyceride). The seven enzymes of triglyceride synthesis are membrane bound and located at the sarcoplasmic … Fatty acids and triglycerides have multiple functions and uses in the human body. In some individuals symptoms don’t appear until adulthood and include seizures, loss of memory, difficulty thinking, or psychiatric abnormalities. These three lipin-1 isoforms are identified as lipin-1α, lipin-1β, and lipin-1γ. The NAD+-dependent mitochondrial enzyme is called malic enzyme 2 and is encoded by the ME2 gene. HHS The glycerol-3-phosphate pathway of triglyceride synthesis is referred to as the Kennedy pathway after Eugene Kennedy who first worked out the pathway of triglyceride synthesis and published his results in 1960. Humans express three genes in this family, PCYT1A (phosphate cytidylyltransferase 1, choline, alpha), PCYT1B (phosphate cytidylyltransferase 1, choline, beta), and PCYT2 (phosphate cytidylyltransferase 2, ethanolamine). In addition, the enzymes encoded by these genes are subject to post-translational and allosteric regulation. The potential therapeutic benefits to reduced MCD activity in the treatment of obesity and diabetes are currently undergoing intensive investigation. The synthesis of fatty acids takes place in the cytosol. The polyphosphoinositides are important intracellular transducers of signals emanating from the plasma membrane. Triglycerides are the main constituents of body fat in humans and other vertebrates, as well as vegetable fat. Endogenous lipolysis is a hormone-sensitive process. Phosphocholine is then converted to CDP-choline by the enzymes of the cytidylyltransferase family. The phosphatidylethanolamines are neutral zwitterions at physiological pH. The process of mitochondrial fatty acid synthesis closely resembles a bacterial type II fatty acid synthesis system (FASII) that involves individual enzymes for each step in the pathway. All of the AGPAT enzymes are integral membrane proteins with the AGPAT1 and AGPAT2 enzymes specifically localized to the ER. Regulation of fat metabolism also occurs through malonyl-CoA induced inhibition of carnitine acyltransferase 1 (CPT1). Both isoforms of ACC are allosterically activated by citrate and inhibited by palmitoyl-CoA and other short- and long-chain fatty acyl-CoAs. Synthesis of Triglycerides from Carbohydrates. NIH The synthesis of phospholipids occurs on the cytoplasmic face of the membranes of the ER. A diet rich in carbohydrates leads to stimulation of both the glycolytic and lipogenic pathways. Mutations in the AGPAT2 gene result in one type of Berardinelli-Seip congenital generalized lipodystrophy (CGL). In many cases the acyl group which was initially transferred to glycerol, by the action of the acyl transferases, is not the same acyl group present in the phospholipid when it resides within a membrane. Cholesterol metabolism page year of life are related to changes in cAMP levels HSD17B8 gene is located on 11p11.2... 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