Lipid Metabolism PDF

Banana Reviewer Plant Lipids LIPID METABOLISM Plant lipids are of two main types: structural and INTRODUCTION storage. The lipids are a...

Banana Reviewer Plant Lipids LIPID METABOLISM Plant lipids are of two main types: structural and INTRODUCTION storage. The lipids are a group of substances found in The structural lipids are present as constituents plant and animal tissues. of various membranes and protective surface layers and make up about 7 % of the leaves of They are insoluble in water but soluble in higher plants. common organic solvents such as benzene, ether and chloroform. The surface lipids are mainly waxes, with relatively minor contributions from long-chain They act as electron carriers, as substrate carriers hydrocarbons, fatty acids and cutin. in enzymic reactions, as components of biological membranes, and as sources and stores of energy. The membrane lipids, present in mitochondria, the endoplasmic reticulum and the plasma In the proximate analysis of foods they are membranes, are mainly glycolipids (40–50 included in the ether extract fraction. %) and phosphoglycerides. Fats and oils are major sources of stored energy in both plants and animals. They are esters of fatty Plant storage lipids occur in fruits and seeds and acids with glycerol. are, predominantly, triacylglycerols. Their physical and chemical nature is determined Over 300 different fatty acids have been isolated by their fatty acid composition; high-molecular from plant tissues, but only about seven are of weight saturated acids confer chemical stability common occurrence. and physical hardness, whereas unsaturated acids confer chemical reactivity and physical softness. The most abundant is linolenic acid; the most common saturated acid is palmitic acid CLASSIFICATION OF LIPIDS and the most common monounsaturated acid is oleic acid. Animal Lipids In animals, lipids are the major form of energy storage, mainly as fat, which may constitute up to 97 per cent of the adipose tissue of obese animals. Banana Reviewer The yield of energy from the complete oxidation Structure of fats of fat is about 39 Fats are esters of fatty acids with the trihydric MJ/kg DM compared with about 17 MJ/kg DM alcohol glycerol. from glycogen, the major carbohydrate form of stored energy. Also referred to as glycerides or acylglycerols. Weight for weight, fat is, therefore, more times When all three alcohol groups are esterified by as effective as glycogen as a stored energy source. fatty acids, the compound is a triacylglycerol (triglyceride): FATS AND OILS Fats and oils are constituents of both plants and animals and are important sources of stored energy. Both have the same general structure but have different physical and chemical properties. The melting points of the oils are such that at ordinary room temperatures they are liquid and they tend to be more chemically reactive than the more solid fats. Structure of fats The term ‘fat’ is frequently used in a general sense to include both groups. As well as its major function of supplying energy, stored fat is important as a thermal insulator and, in some warm-blooded animals, as a source of heat for maintaining body temperature. Triacylglycerols differ in type according to the Note-This is especially important in animals that nature and position of the fatty acid residues. are born hairless, those that hibernate and those that are cold-adapted. Those with three residues of the same fatty acid are termed simple triacylglycerols. Such animals have special deposits of ‘brown fat’ in which all the energy is liberated as heat. When more than one fatty acid is concerned in the esterification, a mixed triacylglycerol results: Banana Reviewer o Note: o Naturally occurring fats o and oils are mixtures of such mixed triacylglycerols. Soya bean oil has been estimated to contain about 79 per cent of mixed triacylglycerols compared with about o 21 per cent of the simple type. Most of the naturally occurring fatty acids have an even number of carbon atom. The majority contain a single carboxyl group and an unbranched carbon chain, which may be saturated or unsaturated. The unsaturated acids could contain one (monoenoic), two (dienoic), three (trienoic) or many (polyenoic) double bonds. Fatty acids with more than one double bond are frequently referred to as polyunsaturated fatty acids (PUFA). The unsaturated acids possess different physical and chemical properties from the saturated acids: they have lower melting points and are more chemically reactive. Banana Reviewer In mammalian depot fat, the proportion of the more unsaturated acids is lower and there is a higher proportion of high-molecular-weight saturated acids such as palmitic and stearic acids. For this reason, fats such as pig lard, and beef and mutton tallow are firm and hard, whereas fish and plant oils are softer and frequently are oils in the true sense. ------------------------------------------------------------------------------------------------------------------------------------------------- The presence of a double bond in a fatty acid Trans form when the atoms lie on opposite sides molecule means that the acid can exist in two forms, depending upon the spatial arrangement of Most naturally occurring fatty acids have the cis the hydrogen atoms attached to the carbon atoms configuration. of the double bond. When the hydrogen atoms lie on the same side of the double bond, the acid is said to be in the cis Essential fatty acids form. Banana Reviewer In 1930, linoleic acid was shown to be These include the prostaglandins, effective in preventing the development of thromboxanes and leukotrienes, hormone- certain conditions in rats given diets almost like substances that regulate many functions, devoid of fat. including blood clotting, blood pressure, smooth muscle contraction and the immune These animals showed a scaly appearance of response. the skin and suboptimal performance in growth, reproduction and lactation; As a general rule, mammals are considered to eventually they died as a result of the have an EFA requirement of 3 % of the deficient diet. energy requirement (3en%) as linoleic acid, although estimates have ranged from 1 per More recent work has demonstrated a wide cent to 15 per cent. range of symptoms in a variety of animals, including some in human beings under The oilseeds are generally rich sources of certain circumstances linoleic acid, and linseed is a particularly good source of -linolenic acid. Arachidonic acid has been shown to have equivalent or even greater activity than Pigs and poultry, which normally have linoleic acid, and linolenic acid is about 1.5 considerable quantities of oilseed residues in times as effective as linoleic acid. Arachidonic their diets, will, therefore, receive an acid is synthesised in the body from linoleic adequate supply of the essential fatty acids. acid Ruminant animals are largely dependent on Such acids have to be supplied in the diet. grasses and forages for their nutritional needs and are thereby supplied with liberal Linoleic acid and α- linolenic acid are thus quantities of linoleic and -linolenic acids. dietary essentials. Although considerable hydrogenation of Linoleic and α-linolenic acids are referred to unsaturated acids to saturated takes place in as the essential fatty acids (EFA). the rumen, with consequent overall reduction of EFA supply (on average 85–95 per cent is Like other polyunsaturated acids, they form lost between the mouth and the small part of various membranes and play a part in intestine), the possibility of ruminants having lipid transport and certain lipoprotein a deficiency is remote. enzymes. A certain proportion of dietary EFA escapes In addition, they are the source materials for hydrogenation (approximately 5–15 per cent the synthesis of the eicosanoids. of dietary intake) and this, allied to very efficient utilisation and conservation of EFA Banana Reviewer by ruminants, is enough to ensure adequacy Eggs are one of the best animal sources and, under normal conditions. among the plants, soya beans contain relatively large amounts. EFA deficiency is rare in human beings although, under certain conditions, it does The phospholipids contain phosphorus in occur in infants, elderly people and people addition to carbon, hydrogen and oxygen. taking drugs that inhibit lipid absorption. WAXES Symptoms associated with Waxes are simple, relatively non-polar lipids essential fatty acid consisting of a long-chain fatty acid combined deficiencies with a monohydric alcohol of high molecular weight. They are usually solid at ordinary temperatures. The fatty acids present in waxes are those found in fats. Waxes are widely distributed in plants and animals, where they often have a protective function. The hydrophobic nature of the wax coating reduces water losses caused by transpiration PHOSPHOLIPIDS in plants, and provides wool and feathers with waterproofing in animals. The role of the phospholipids is primarily as constituents of the lipoprotein complexes of Among better-known animal waxes are biological membranes. lanolin, obtained from wool, and spermaceti, a product of marine animals. They are widely distributed, being particularly abundant in the heart, kidneys and nervous In plants, waxes are usually included in the tissues. cuticular fraction, where they form a matrix in which cutin and suberin are embedded. Myelin of the nerve axons, for example, contains up to 55 per cent of phospholipid. The term wax is used here in the collective sense and, although true waxes are always Banana Reviewer present, the major part is made up of a  It is particularly important in the complex mixture of substances. myelinated structures of the brain and central nervous system and may Note constitute up to 170 g/kg.  Alkanes make up a large proportion of  It is the precursor of the steroid the whole, with odd-chain compounds hormones. predominating.  It is also the precursor of the bile acids.  Branched-chain hydrocarbons, aldehydes, free fatty acids and various Normal concentrations in the blood plasma ketols are commonly occurring though are in the range 1200–2200 mg/l. minor constituents. Cholesterol is very insoluble and prolonged  Free alcohols are usually of minor high levels in blood result in its deposition on importance but may form up to half of the walls of the blood vessels. some waxes. These deposits eventually harden to The waxes are resistant to breakdown and atherosclerotic plaque. are poorly utilised by animals. This narrows the blood vessel and serves as a Their presence in foods in large amounts site for clot formation and may precipitate leads to high ether extract figures and may myocardial infarction or heart attack. result in the nutritive value being overestimated. Note:  It has been known for many years that STEROIDS one of the most important dietary factors regulating serum cholesterol Cholesterol levels is the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids Cholesterol is a zoosterol that is present in all (SFA). animal cells.  The SFA increase and the PUFA decrease It has a low solubility in water, about 0.2 cholesterol levels, except for the trans mg/100 ml. PUFA, which have a similar effect to the It is the major sterol in human beings and is SFA. important as a constituent of various 7-Dehydrocholesterol biological membranes. Banana Reviewer This substance, which is derived from contains high concentrations of free cholesterol, is important as the precursor of cholesterol, about 390 mg/100 ml. vitamin D3, which is produced when the sterol is exposed to ultraviolet light. The bile salts assist, along with the detergent action of phospholipids, in preventing the cholesterol in the bile fluid from crystallising out of solution. They act as emulsifying agents in preparing dietary triacylglycerols for hydrolysis, by pancreatic lipase, in the process of digestion. Ergosterol They facilitate the absorption, from the digestive tract, of the fat-soluble vitamins. This phytosterol is widely distributed in brown algae, bacteria and higher plants. Steroid hormones It is important as the precursor of These include the female sex hormones ergocalciferol or vitamin D2, into which it is (oestrogens), the male sex hormones converted by ultraviolet irradiation. (androgens) and progesterone, as well as cortisol, aldosterone and corticosterone, Bile acids which are produced in the adrenal cortex. The bile acids are synthesised from The adrenal hormones have an important cholesterol and this constitutes the major end role in the control of glucose and fat point of cholesterol metabolism. metabolism. Under physiological conditions the acids exist as salts. LIPID DIGESTION AND They are produced in the liver, stored in the TRANSPORT gall bladder and secreted into the upper small intestine. Many of the organic components of food are in the form of large insoluble molecules, which They are important in several ways: have to be broken down into simpler compounds before they can pass through the They provide the major excretory pathway for mucous membrane of the alimentary canal into cholesterol, which cannot be catabolised to the blood and lymph. carbon dioxide and water by mammals. Bile The breakingdown process is termed ‘digestion’, and the passage of the digested Banana Reviewer nutrients through the mucous membrane an organ for the digestion of food but also for ‘absorption’. storage. The processes important in digestion may be grouped into Viewed from the exterior, the stomach can be o mechanical seen to be divided into… o chemical CARDIA (ENTRANCE) o microbial Mechanical FUNDUS o mastication o muscular contractions of the alimentary PYLORUS (TERMINUS) canal The inner surface of the stomach is increased in Chemical area by an infolding of the epithelium and has four o enzymes in the various digestive juices distinct areas. Microbial also enzymic The gastric juice consists of: o action of bacteria, protozoa and fungi, o Water (ruminants) o Pepsinogens o in monogastric animals, microbial o Inorganic salts activity occurs mainly in the large o Mucus intestine, although there is a low level o Hydrochloric acid of activity in the crop of birds and the o The intrinsic factor important for the stomach and small intestine of pigs. efficient absorption of vitamin B12. DIGESTION IN MONOGASTRIC ANIMALS DIGESTION IN THE SMALL INTESTINE The digestive tract can be considered as a tube WHERE LIPID DIGESTION OCCURS extending from mouth to anus, lined with The SI is lined with specialized epithelial cells mucous membrane, whose function are… that can absorb nutrients and contains an o Prehension array of enzymes that break down the food for o Ingestion absorption called LIPASES secreted by the o Comminution pancreas or found naturally lining the o Digestion intestines. o Absorption of food, o Elimination of solid waste material. PROBLEM WITH FAT DIGESTION? DIGESTION IN THE STOMACH Notably these lipase enzymes must function in an aqueous environment as with most of the THE STOMACH of the adult pig consists of a body. simple compartment, which functions not only as Banana Reviewer This poses a problem because fat molecules Bile is secreted by the liver and passes to the are very hydrophobic and are therefore duodenum through the bile duct. insoluble in an aqueous environment. In all farm animals except the horse, bile is These hydrophobic molecules group together stored in the gall bladder until required. instead of dissolving (fatty droplets). The bile salts play an important part in digestion by activating pancreatic lipase and emulsifying fats. Bile is essentially a detergent for food. Soap has a hydrophilic and a hydrophobic functional groups in its molecule. o This allows bile to emulsify or solubilize the fatty molecule thus breaking it up into tinier pieces, increasing the surface area on which the lipase enzymes can act upon these fat molecules. recall grease gets removed easily with soap Notes tha with water) When we refer to a fat molecule, we think of TAGs PANCREATIC ENZYMES (LIPASES) Glycerol backbone (E) The breakdown of fats is achieved by pancreatic lipase. This enzyme does not Attached via O to three acyl groups (which, completely hydrolyse triacylglycerols and the remember are a C = O and many C and H action is aided by emulsification, which is /\/\/\/\/\/ brought about by the action of bile salts The key idea here is that because there are many C Specifically, these lipase enzymes break down and H, we have a very hydrophobic molecule, and the TAG molecules by cleaving the molecules so these molecules will not be dissolved in the at the ester linkages by adding water molecule aqueous environment of the SI. among these bonds. These hydrophobic molecules group together The end results of lipase action on TAG are: instead of dissolving (fatty droplets) a free glycerol backbone with a hydroxyl BILE group (accepted a H from water) and a carboxylic acid group (because we To resolve this problem, the body secretes are adding the remaining hydroxyl group BILE from the liver. Banana Reviewer from the water to these molecules), which The first step is to turn these fatty acids back we call fatty acids into TAGs upon absorption o Reforming ester linkages The way the body packs these TAGs is through a carrier molecule called LIPOPROTEIN, specifically, a CHYLOMICRON Note o you essentially want to pack them in a compact unit to send them off to various tissues. o Chylomicron contains TAGs + At this point these fatty acid molecules are hydrophobic substances, like cholesterol small enough to be able to diffuse into the in the core of a protein molecule. intestinal cell. CHYLOMICRON ABSORPTION AND The protein layer has a polar head that can TRANSPORT OF LIPIDS interact with aqueous environments inside the blood stream, for example. But inside, they are After digestion fats are present in the small hydrophobic enough to keep the hydrophobic intestine in the solubilised form of mixed molecules within. micelles. The next step is to make sure the chylomicrons Efficient absorption requires a rapid movement leave the cell. The villi cells of the small of the highly hydrophobic molecule through the intestine lining are surrounded by capillaries unstirred water layer adjacent to the mucosa. and specialized lymphatic capillaries called This is the rate limiting stage of absorption. lacteals. The mixed bile salt micelles, with their The chylomicrons are big, bulky molecules and hydrophilic groups, aid this process cannot go through the capillaries and instead Absorption across the brush border membrane pass through the lacteals to be able to be of the intestinal cells is by passive diffusion and distributed to different tissues. is at its maximum in the jejunum. The bile salts are absorbed by an active process in the distal ileum. The fatty acids are delivered to various tissues in the body through the bloodstream. LIPID ABSORPTION AND Most notably the adipose tissues where we store fat for later energy use. TRANSPORT Banana Reviewer When chylomircrons reach the capillary, o VLDLs can also be acted upon by enzymes at the capillary walls called lipoprotein lipases when they reach the LIPOPROTEIN LIPASE breaks down the capillary bed to liberate the fatty acids. chylomicron and also breaks down the TAGs into simpler fatty acids and free glycerol WHAT HAPPENS TO THE FATS STORE IN THE backbone. The fatty acids are utilized by various cells in ADIPOSE CELLS? the body with notable exceptions of the brain The adipose cells have hormone receptors on (fatty acids cannot cross BBB), and RBCs (no their surfaces that can detect the amount of mitochondria to metabolize fatty acids). hormones in the body. The fatty acids are utilized mostly by adipose Right after a meal, insulin is abundant, but cells for storage by turning them back into TAGs several hours after, insulin levels begin to fall. storing them as fatty droplets. When insulin level decreases several hours CHYLOMICRON REMNANTS after a meal, glucagon levels begin to increase Chylomicron remnants persist after action of in response to having not enough blood lipoprotein lipase on chylomicrons and still glucose. contain useful materials. This stimulates the hormone receptors in the The liver plays a big role in reabsorbing these adipose cells that sends a signal inside the cell chylomicron remnants through the production to release the fatty acids they contain into the of VLDLs. blood stream. In the blood stream, the hydrophobic fatty acid VLDVs molecules travel alongside the large protein in Every digestive process passes through the the blood called albumen (produced also by the liver. liver) and can be used by different tissues in the Glucose → either used for cellular energy (ATP), body. stored as glycogen, or in instances of excess The enzyme that catalyzes the breakdown of glucose, can be converted to fatty acids. TAGs in the adipose cells are called hormone- The liver has a similar function with the small sensitive lipase. intestines. One of the biggest consumer of free fatty acids o it converts these fatty acids into TAGs liberated by hormone-sensitive lipases is the and packs them in specialized protein liver. carrier molecules similar to o During the time of fasting after a meal chylomicrons, called very low density when the body needs to maintain blood lipoprotein (VLDL). glucose for the brain and RBCs that o VLDL contains fatty acids converted cannot use fatty acids, the process of from glu, fatty acids, and cholesterol gluconeogenesis occurs in the liver from chylomicron remnants. Banana Reviewer o This needs a lot of ATP and the major Calcium salts of fatty acids have little effect on fuel present in the body during this time rumen fermentation and are used as fat are fats, and that is where the liver supplements for ruminants. takes the necessary ATP to fuel gluconeogenesis. FATTY ACID SYNTHESIS DIGESTION OF LIPIDS IN The ultimate goal of fat metabolism is to be able to deliver fatty acids (monomer subunits RUMNANTS of TGA) directly into the bloodstream, where they can eventually reach capillary beds. The triacylglycerols present in the foods Through the capillaries, the fatty acids diffuse consumed by ruminants contain a high to surrounding tissues where they are oxidized proportion of residues of the C18 for cellular energy in the form of ATP. polyunsaturated acids, linoleic and linolenic. These triacylglycerols are to a large extent hydrolysed in the rumen by bacterial lipases. SOURCES OF TAGs AND Once they are released from ester combination, FFAs the unsaturated fatty acids are hydrogenated by bacteria, yielding first a monoenoic acid and, Food- small intestines digest food and package ultimately, stearic acid. it into protein carrier molecules called The rumen microorganisms also synthesise chylomicrons that travel through the lymphatic considerable quantities of lipids, which contain vessels. some unusual fatty acids (such as those Adipose cells- several hours after a meal when containing branched chains); these acids are insulin starts to drop and glucagon rises, eventually incorporated in the milk and body adipose cells are signalled to release the free fats of ruminants. fatty acids (FFAs) into the bloodstream that The capacity of rumen microorganisms to attach themselves to albumin in the digest lipids is strictly limited. bloodstream. The lipid content of ruminant diets is normally low (i.e. 50 g/kg), and if it is increased above Synthesizing fatty acids directly in the liver 100 The liver cells have enzymes that are able to g/kg the activities of the rumen microbes are convert excess glucose (i.e. reduced. glucose not used in ATP and glycogen synthesis) o The fermentation of fibre is retarded into fatty acids. and food intake falls The liver packages these FAs into TAGs and Saturated fatty acids affect rumen packages them with cholesterol into specialized fermentation less than do unsaturated fatty protein molecule carriers similar to acids. chylomicrons, the very low density lipoprotein Banana Reviewer (VLDL), which are distributed to different called NADH and FADH2 which shuttle their tissues via the bloodstream. electrons from the oxidation process in the Krebs cycle to the electron transport chain FATTY ACID SYNTHESIS located in the inner membrane of the mitochondria. And fro there, ATP is produced Important compartments in cell via oxidative phosphorylation. o Cytoplasm o Mitochondria ▪ inner and outer membrane ▪ electron transport chain is CONVERTING GLUCOSE TO located in the inner membrane ▪ site of the Krebs cycle which FATTY ACID continues to break down glucose Acetyl CoA in the mitochondrial inner matrix is following glycolysis in the a precursor to FA synthesis. cytoplasm ALL the enzymes necessary for FA synthesis is in the cytoplasm. GLYCOLYSIS IN However, Acetyl CoA is in the mitochondria and CYTOPLASM there are no protein carriers to transport it through the mitochondrial membrane. Glucose (6C)→ Pyruvate (3C)→ Transported in There is, however, a protein carrier for the the mitochondria, where pyruvate molecule, citrate, tricarboxylate translocase. dehydrogenase (PDH) oxidizes and removes o 6C Citrate contains 2C acetyl CoA and 3C one C OAA. atom from pyruvate → Acetyl CoA (2C) o Remember that most fatty acids are 2C Acetyl CoA molecule is not done being repeating C-H backbone, and we want broken down. The energy is extracted in the to basically be able to link together C-C Krebs Cycle. bonds. And the Acetyl CoA are simply a In the Krebs Cycle, a 4C molecule, oxaloacetate pair of C-C bonds that we can ultimately (OAA) combines with a single molecule of 2C link together. Acetyl CoA to produce a 6C molecule called citrate. Note: Citrate continues to be modified, oxidized, and broken down to returns to form OAA, which means that we lose a couple of carbon atoms (as 2 molecules of CO2), and also forms a number of reduced electron carrier molecules  Banana Reviewer The PPP may be the primary process to produce NADPH, but the conversion of OAA into pyruvate also produces NADPH. one of the uses of NADPH, is that because it can serve as a reducing power to help with anabolic reactions (building up molecules, including…FA SYNTHESIS!) Once citrate reaches the cytoplasm, there is an FATTY ACID SYNTHESIS IN enzyme that breaks the citrate molecule back into OAA and Acetyl CoA, ATP-citrate lyase THE CYTOPLASM OAA is not going to be used for FA synthesis Multiple Acetyl CoA (precursor molecule) is and gets recycled: it gets converted back to needed to synthesize a FA. Since this is an pyruvate! anabolic process, ATP is used as well as Once pyruvate goes back into the reducing powers to form the C-C bonds. mitochondria, it gets converted into Acetyl CoA NADPH is a reducing power that can be and the entire cycle continues produced by the Pentose Phosphate Pathway but can also be provided by the conversion on OAA to pyruvate. Acetyl-CoA, is carboxylated to malonyl-CoA. Acetyl-CoA Carboxylase catalyzes the 2-step reaction by which acetyl-CoA is carboxylated to form malonyl-CoA. Acetyl-CoA Carboxylase, which converts acetyl- CoA to malonyl-CoA, is the rate-limiting step of the fatty acid synthesis pathway. NOTEl: - it is important to note that in converting OAA (4 C) into pyruvate (3 C), we are actually losing a C as CO2 during this process, and simultaneously, oxidizing that intermediate and therefore reduce a molecule of NADP+ into NADPH (a product of the pentose phosphate pathway). The malonyl-coenzyme A then reacts with acyl- carrier protein (ACP), in the presence of malonyl- Banana Reviewer CoA-ACP transacylase, to give the malonyl–ACP Note: complex. Priming by acetyl CoA- An acyl carrier protein, ACP, Acetylcoenzyme A is then coupled with ACP in plays a key role in the synthesis of fatty acids. First, the presence of acetyl-CoA-ACP transacylase, and it must be primed with acetyl CoA, forming Acetyl this reacts with the malonyl–ACP, the chain length ACP. being increased by two carbon atoms to give the butyryl–ACP complex. 1b. Transfer to β-ketoacyl synthase- The acetyl group is passed temporarily to a synthase enzyme, The butyryl–ACP complex then reacts with and malonyl–ACP complex, resulting in further elongation of the chain by two carbon atoms to Malonyl CoA binds with the synthase enzyme give caproyl–ACP. forming malonyl ACP, and releasing CoA. Chain elongation takes place by successive Condensation- The acetyl group from the synthase reactions of the fattyacyl–ACP complexes with condenses with the malonyl ACP which releases a malonyl–coenzyme A until the palmitoyl–ACP molecule of CO2. complex is produced, when it ceases. First reduction. NADPH + H+ reducesthe molecule, producing D-β-Hydroxybutyryl-ACP. Dehydration- gives rise to an unsaturated fatty acid, Crotonyl-ACP. Second reduction- a second reduction saturates the molecule again, producing butyryl-ACP. Transfer to β-ketoacyl synthase. Malony transfer The overall reaction can be presented as: Banana Reviewer The butyryl–ACP complex then reacts with malonyl–ACP complex, resulting in further elongation of the chain by two carbon atoms to give caproyl–ACP. Chain elongation takes place by successive reactions of the fattyacyl–ACP complexes with malonyl–coenzyme A until the palmitoyl–ACP complex is produced, when it ceases. Fat as an energy source The store of triacylglycerol in the body is mobilised to provide energy by the action of In assessing the energy requirements of the lipases, which catalyse the production of glycerol process, the energy cost of producing malonyl- and fatty acids. coenzyme A from acetyl-coenzyme A must be The glycerol is glycogenic and enters the taken into account and can be presented as: glycolytic pathway as dihydroxyacetone phosphate. By the reverse of the aldolase reaction → fructose-1,6-diphosphate. Fructose-1,6-diphosphate is then converted to LIPID METABOLISM glucose by the action of hexose diphosphatase, Banana Reviewer glucose-6-phosphate isomerase and glucose-6- phosphatase. If the glucose is used to produce energy, we may assess the efficiency of glycerol as an energy source: On the other hand, the dihydroxyacetone phosphate may enter the glycolytic pathway and be metabolised via pyruvate and the tricarboxylic β-oxidation of fatty acids to acid cycle to carbon dioxide and water, with energy Acetyl CoA being released. By far the most important source of energy provided by triacylglycerols is derived from the fatty acids. The major pathway for fatty acid degradation is β-oxidation, which results in a progressive Banana Reviewer shortening of the carbon chain by removal of two  The fattyacyl-CoA is then transferred into carbon atoms at a time. the mitochondria as a complex with carnitine and is regenerated there. Two important cellular compartments in Fatty Acid Oxidation  Note: o Cytoplasm o CARNITINE, a molecule in the cell has a o Mitochondria hydroxyl group. The hydroxyl group’s Recall that fatty acid synthesis takes place in oxygen can form a bond with the C on the the cytoplasm, where the enzymes required for Acyl CoA. The leaving group form this that process are located. reaction is the Coenzyme group so we The enzymes located for the oxidation of fatty come up with a carnitine bonded with the acids are located inside the mitochondria. fatty acid (acyl carnitine). o The enzyme that catalyzes this is carnitine- ACTIVATION STEP enzyme transferase 1 (rate limiting step) The first stage of β-oxidation is the reaction of o The acyl carnitine molecule goes through the fatty acid with coenzyme A in the presence the outer mitochondrial membrane of ATP and fattyacyl-CoA ligase to give an acyl- through pores, and through the inner coenzyme A. mitochondrial membrane through protein Notes: transporters called acyl carnitine FA→carboxyl group + long chains of C and H translocase that comprise the fatty acid tail (R) The FA molecule has to be “activated” with another molecule to be able to transport it to OXIDATION STEP the mitochondria The fattyacyl-CoA then undergoes a series of FA + Coenzyme A (CoA-SH) = Acyl CoA reactions to give an acyl-coenzyme A with two less (“activated FA”) carbon atoms than the original and a mole of The process has to have an input of chemical acetyl-CoA is released. energy, so the reaction is coupled to the hydrolysis of ATP. We usually think of it as hydrolysis of ATP to ADP, but in this case it goes all the way to the monophosphate group (AMP) + a pyrophosphate group (PP) TRANSPORT STEP Banana Reviewer can shuttle them to the electron transport chain to produce ATP. These electron carrier molecules are FAD and NAD, which when accepting electrons become reduced to FADH and NADH H+ The electron transport chain is located in the inner mitochondrial membrane and so the electron carrier molecules can become reoxidized into their oxidized form and the cycle can continue.e II Note: Upon entry of acyl carnitine to the mitochondrial membrane, the carnitine group is cleaved from the molecule by action of carnitine acyl transferase 2 (a coenzyme A molecule in the mitochondria binds with the acyl group of the acyl carnitine with the sulfur group as the nucleophile, displacing carnitine and forming a carnitne with a hydroxyl group and an acyl CoA group (see transport step’s beginning molecules) The carnitine group can actually return to the cytoplasm to be recycled to help transport more fatty acids to the mitochondrial matrix The acyl CoA molecule undergoes cycles of repeated steps with the enzyme found in the mitochondrial matrix These cycles consist of four steps that end up producing a single molecule of Acetyl CoA + an acyl CoA chain that is now 2C shorter than before. PPT NOTES The production of Acetyl CoA involves oxidation— The first stage of -oxidation is the reaction of the in oxidation, we lose electrons so we need electron fatty acid with coenzyme A in the presence of ATP carrier molecules to accept those electrons so they and fattyacyl-CoA ligase to give an acylcoenzyme A. Banana Reviewer This occurs in the cell cytoplasm; the fattyacyl-CoA is then transferred into the mitochondria as a complex with carnitine and is regenerated there. It then undergoes a series of reactions to give an acyl-coenzyme A with two less carbo atoms than the original and a mole of acetyl-CoA is released. β-oxidation of fatty acids to Acetyl CoA During the splitting off of the two-carbon acetyl- coenzyme A, the equivalent of 4 moles of ATP is produced. The remaining acyl-coenzyme undergoes the same series of reactions and the process continues until the carbon chain has been completely converted to acetyl-coenzyme A. β-oxidation of Palmitate (16-C) β-oxidation of fatty acids to Acetyl CoA This enters the tricarboxylic acid cycle and is oxidised to carbon dioxide and water, each mole of acetyl-CoA so metabolised giving 10 moles of ATP. Since the initial ligase reaction is necessary only once for each molecule, more ATP is produced for the same expenditure of energy by the oxidation of long- rather than short-chain acids