makalah metabolisme lipid

METABOLISM LIPID

Lipid metabolism can be defined as the processes that involve the creation and degradation of lipids. The types of lipids involved include bile salts, cholesterols, eicosanoids, glycolipids, ketone bodies, fatty acids, phospholipids, sphingolipids, steroids, triacylglycerols etc. The major aspects of lipid metabolism are involved with Fatty Acid Oxidation to produce energy or the synthesis of lipids which is called Lipogenesis. Lipid metabolism is closely connected to the metabolism of carbohydrates which may be converted to fats. The metabolism of both is upset by diabetes mellitus.
The first and the basic step in lipid metabolism is the hydrolysis of thelipid in the cytoplasm to produce glycerol and fatty acids. Since glycerol is a three carbon alcohol, it is metabolized quite readily into an intermediate in glycolysis, dihydroxyacetone phosphate. The last reaction is readily reversible if glycerol is needed for the synthesis of a lipid. The hydroxyacetone, obtained from glycerol is metabolized into one of two possible compounds. Dihydroxyacetone may be converted into pyruvic acid through the glycolysis pathway to make energy. In addition, the dihydroxyacetone may also be used in gluconeogenesis to make glucose-6-phosphate for glucose to the blood or glycogen depending upon what is required at that time. Fatty acids are synthesized from carbohydrates and occasionally from proteins. Actually, the carbohydrates and proteins have first been catabolized into Acetyl CoA. Depending upon the energy requirements, the acetyl CoA enters the citric acid cycle or is used to synthesize fatty acids in a process known as Lipogenesis.
Lipid metabolism is nothing but a series of chemichal reaction, process responsible for the synthesis and breakdown of glycerides, sterols and phospholipids. Lipids are mostly comprised of oxygen, hydrogen and carbon. Glycerides are available in the form of fat which is stored as a fuel purpose, and the remaining two forms sterols and phospholipids where found as cholesterol. Glycerides exist in two forms, chylomicrons and lipoproteins for the purpose of yielding energy when consumed by the cell. Before consuming the glycerides, it must be hydrolyzed as it cannot be taken directly by the tissues.
By the use of carbohydrates, fat cells (adiposities), amino acids and diet, we can obtain fatty acids. These fatty acids are supplied through the body by the blood stream in the form of chylomicrons which are the easiest form to transform energy to the required cells.
Lipolysis, ketosis, lipogenesis and betaoxidation are the metabolic pathways of lipid metabolism. Beta oxidation and Lipolysis were carried in the cell mitochondria for the removal of two carbons in the form of acetyl CoA from fatty acid cycle, and later enters into the citric acid cycle to produce energy packets (Adenosine triphosphate), water and co2. These are the output products of Lipolysis and beta oxidation metabolic pathways.
If the rate of change of ketones formation by the liver is in high rate due to prolonged starvation, then this ketosis metabolic pathway occurs. This process also occurs when large amount of fat foods are consumed with less carbohydrates content.
The metabolic pathway of lipogenesis occurs in the cytosol of cell membrane. Lipogenesis causes Triglyceride (basic form of glycerides) to synthesize in liver, intestinal mucosa and muscle tissues as these are the main sites for the occurrence of this process. The production of fatty acids is done from hydrolysis of some fats, oxidation of amino acids, glucose and also from the synthesis of acetyl CoA.
Lipid is the only nutrient that contains hydrogen which plays the key role for the formation of glycerides, sterols and phospholipids. Lipids are the organic compounds of fatty acids, glycerolipids, glycerophospholipids, sterol lipids, prenol lipids, saccharolipids and polyketides which are the essential nutrients in building the muscle tissue and organs. Glycerolipids are very essential for building the cell structures. If the presences of glycerolipids are in excess state then it was converted into fat and later used for energy metabolism.
The body exposes to prolonged starvation or illness due to the breakdown of lipids by the inadequate supply of energy .Brain tissues uses the preference of liver for utilizing the organic compounds of lipids in it. Liver cells and kidney cells are the only two organs to contain the lipogenesis pathway which are used for the conversion of this organic compound into fats.
Lipid catabolism is the process of breaking down the lipid groups (glycerides, sterols and phospholipids) into smaller units for the easy transfer of energy through blood to the cells. Lipid catabolism is also referred to as digestion process of nutrients. Carbon dioxide, water and ATP are the final products of lipid catabolism.
lipid Anabolism is the process of grouping the smaller lipid groups into larger molecules for building up the organs and muscle tissues.
Lipid metabolism disorder causes severe damage to the major organs due to accumulation of excess fatty acids in cells and tissues of brain, liver, nervous system, sple spleen and bone marrow. Neurological complications, pains in arms and legs, eye paralysis and muscle tone disease are caused due to the disorder of lipid metabolism.
Neurological complications, pains in arms and legs, eye paralysis and muscle tone disease are caused due to the disorder of lipid metabolism.
The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human.
We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR) – attenuated total reflection (ATR) detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005~3015 cm-1, of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA)-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm-1.
The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively. TIR-ATR (Fourier-transform infrared spectroscopy with attenuated total reflection) technique is an established measurement system for analysis of chemical and biological materials and many applications have been developed. About 20 years ago this FTIR technique was applied to the microscopy for development of micro-spectroscopy and imaging of chemical and biomedical materials, as this technique could be used for many kinds of materials in solid or liquid non-destructively. However, this FTIR measurement in millimeter scale, which may be especially important for analysis of macroscopic human body, has not been improved much so far. Although many important data have been accumulated concerning to the measurement of chemical and pathophysiological changes of human tissues and biomolecules with FTIR, the development of FTIR instrument for application to human body and tissues in vivo has not been advanced. In order to diagnose human body, especially the surface of skin or tissues non-invasively and easily, FTIR technique has a significant potential and it may be applied to detect important biomolecules, even though they are mixed in biological tissues and the depth profile in the skin may not be obtained. It could be used sophisticated statistical methods, such as partial least squares regression or other chemometrics for analysis of components in complex mixtures. This FTIR method thus may be used, if it is available for all people, for chemical diagnosis of human body as such that the hand-held blood pressure measurement instrument was used for physical diagnosis of human vessels for all people at home.
FTIR-ATR technique may have several merits to measure changes of biomolecules on the surface of human body or tissues when comparing with laser Raman micro-spectroscopy. The latter laser Raman method may employ near-infrared laser and large hardware including photomultiplier, and the illumination of laser light on human skin, especially face skin, may be largely restricted. On the other hand, FTIR-ATR may be applicable to human body without risk. The application of FTIR-ATR to human skin (stratum corneum) was reported. Recently a handy type of FTIR-ATR system was developed and this type would be applicable to investigation of human body easily if the target surface site to be measured could be correlated with the change of body conditions and analysis software was suitably used.
We focus now on the lipid metabolism of human body, and if we could develop FTIR-ATR system for measurement of lipid metabolism of human body non-invasively, this would greatly contribute to the advancement of management of people's health. However, the lipids on the usual skin surface may be mainly originated from sebum, and the sebum lipids may not reflect immediate changes of human body lipids. Normally the ingested lipids with foods were digested and adsorbed through intestine to blood and to liver, and resorbed through vessels to peripheral tissues, including skin tissues. It may be essential to find out sites of human body, especially skin tissues, where the lipid and fatty acid changes of blood were reflected nearly immediately, to measure non-invasively with FTIR-ATR.
We found, as shown in this paper, that the change of human lip surface lipid compositions reflected well that of ingested lipids, and the changes of lipids and fatty acids were really detected with FTIR-ATR in situ. This paper is the first to demonstrate that the measurement of lip surface lipids with FTIR-ATR non-invasively could show the actual metabolic rate of fatty acid from the intake of food to the appearance in the peripheral tissue.
Fatty acids are an important source of energy and adenosine triphosphate (ATP} for many cellular organisms. Excess fatty acids, glucose, and other nutrients can be stored efficiently as fat. Triglycerides yield more than twice as much energy for the same mass as do carbohydrates or proteins. All cell membranes are built up of phospholipids, each of which contains two fatty acids. Fatty acids are also used for protein modification. The metabolism of fatty acids, therefore, consists of catabolic processes that generate energy and primary metabolites from fatty acids, and anabolic processes that create biologically important molecules from fatty acids and other dietary carbon sources.
A. Digestion and transport
Fatty acids are usually ingested as triglycerides, which cannot be absorbed by the intestine. They are broken down into free fatty acids and monoglycerides by pancreatic lipase, which forms a 1:1 complex with a protein called colipase, which is necessary for its activity. The activated complex can work only at a water-fat interface. Therefore, it is essential that fatty acids (FA) be emulsified by bile salts for optimal activity of these enzymes. People having had their gallbladder removed due to gall stones have, as a consequence, great difficulty digesting fats.
The digestion products of triglycerides are absorbed primarily as free fatty acids and 2-monoglycerides, but a small fraction are absorbed as free glycerol and as diglycerides. Once across the intestinal barrier, they are reformed into triglycerides and packaged into chylomicrons or liposomes, which are released into the lacteals, the capillaries of the lymph system and then into the blood. Eventually, they bind to the membranes of hepatocytes, adipocytes or muscle fibers, where they are either stored or oxidized for energy. The liver acts as a major organ for fatty acid treatment, processing chylomicron remnants and liposomes into the various lipoprotein forms, in particular VLDL and LDL. Fatty acids synthesized by the liver are converted to triglyceride and transported to the blood as VLDL. In peripheral tissues, lipoprotein lipase digests part of the VLDL into LDL and free fatty acids, which are taken up for metabolism.
This is done by the removal of the triglycerides contained in the VLDL. What is left of the VLDL absorbs cholesterol from other circulating lipoproteins, becoming LDLs. LDL is absorbed via LDL receptors. This provides a mechanism for absorption of LDL into the cell, and for its conversion into free fatty acids, cholesterol, and other components of LDL. The liver controls the concentration of cholesterol in the blood by removing LDL. Another type of lipoprotein known as high-density lipoprotein, or HDL collects cholesterol, glycerol and fatty acids from the blood and transports them to the liver. In summary:
1. Chylomicrons carry diet-derived lipids to body cells
2. VLDLs carry lipids synthesized by the liver to body cells
3. LDLs carry cholesterol around the body
4. HDLs carry cholesterol from the body back to the liver for breakdown and excret
When blood sugar is low, glucagon signals the adipocytes to activate hormone-sensitive lipase, and to convert triglycerides into free fatty acids. These have very low solubility in the blood, typically about 1 μM. However, the most abundant protein in blood, serum albumin, binds free fatty acids, increasing their effective solubility to ~ 1 mM. Thus, serum albumin transports fatty acids to organs such as muscle and liver for oxidation when blood sugar is low.
B. Transport and oxidation
The neutral lipids stored in adipocytes (and in steroid synthesizing cells of the adrenal cortex , ovary, and testes) in the form of lipid droplets, with a core of sterol esters and triacylglycerols surrounded by a monolayer of phospholipids are coated with Perilipin, a protein that acts as a protective coating from the body’s natural lipases, such as hormone-sensitive lipase,[1]. However, when a hormone such as epinepherine and glucagon are secreted in response to low levels of glucose, this triggers an intracellular secondary messenger cascade which phosphorylates hormone-sensitive lipase to break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis.
The free fatty acids the move into the blood stream where they are bound by serum albumin and transported to the tissue needing fuel. Once the fatty acids reach the target tissue, they are released by serum albumin and cross into the cytosol. The enzymes used in fatty acid oxidation in animal cells are located in the mitochondrial matrix (as was demonstrated by Eugene P. Kennedy and Albert Lehninger in 1948). Free fatty acid chains of more than 12 carbons require the help of membrane transporters to cross into the membrane into the mitochondria, where they undergo Fatty acid degredation.
Fatty acid degradation is the process in which fatty acids are broken down, resulting in release of energy. It includes three major steps:
• Activation and ransport into the mitochondria
• β-Oxidation
• Electron transport chain
Fatty acids are transported across the outer mitochondrial membrane by carnitine-palmitoyl transferase I (CPT-I), and then couriered across the inner mitochondrial membrane by carnitine. Once inside the mitochondrial matrix, fatty acyl-carnitine reacts with coenzyme A to release the fatty acid and produce acetyl-CoA. CPT-I is believed to be the rate limiting step in fatty acid oxidation.
Once inside the mitochondrial matrix, fatty acids undergo β-oxidation. During this process, two-carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. Acetyl-CoA can then enter the TCA cycle, which produces NADH and FADH2. NADH and FADH2 are subsequently used in the electron transport chain to produce ATP, the energy currency of the cell.
Besides β-oxidation, other oxidative pathways are sometimes employed. α-Oxidation is used for branched fatty acids that cannot directly undergo β-oxidation. The smooth ER of the liver can perform ω-oxidation, which is primarily for detoxification but can become much more prevalent in cases of defective β-oxidation. Fatty acids with very long chains (20 or more carbons) are first broken down to a manageable size in peroxisomes.


C. Regulation and control
It has long been held that hormone-sensitive lipase (HSL) is the enzyme that hydrolyses triacylglycerides to free fatty acids from fats (lipolysis). However, more recently it has been shown that at most HSL converts triacylglycerides to monoglycerides and free fatty acids. Monoglycerides are hydrolyzed by monoglyceride lipase; adipose triglyceride lipase may have a special role in converting triacylglycerides to diacylglycerides, while diacylglycerides are the best substrate for HSL.[3]. HSL is regulated by the hormones insulin, glucagon, norepinephrine, and epinephrine.
Glucagon is associated with low blood glucose, and epinephrine is associated with increased metabolic demands. In both situations, energy is needed, and the oxidation of fatty acids is increased to meet that need. Glucagon, norepinephrine, and epinephrine bind to G protein-coupled receptors that activate adenylate cyclase to produce cyclic AMP. As a consequence, cAMP activates protein kinase A, which phosphorylates (and activates) hormone-sensitive lipase.
When blood glucose is high, lipolysis is inhibited by insulin. Insulin activates protein phosphatase 2A, which dephosphorylates HSL, thereby inhibiting its activity. Insulin also activates the enzyme phosphodiesterase, which breaks down cAMP and stops the re-phosphorylation effects of protein kinase A.
For the regulation and control of metabolic reactions involving fat synthesis, see lipogenesi