LIPID

FAT METABOLISM

A. UNDERSTANDING METABOLISM
Metabolism (Greek: metabolismos, changes) are all chemical reactions that occur in organisms, including that occurs at a cellular level.
Metabolism is the overall reaction occurring in the cell, including the process of decomposition and synthesis of chemical molecules that produce and require heat (energy) and catalyzed by enzymes
Metabolism includes:
1. Stripe of synthesis (anabolisme / endorgenik) combine small molecules into macromolecules is more complex, requires energy supplied by ATP hydrolysis.
2. Stripe of degradative (catabolism / eksorgenik) break down complex molecules into simpler molecules, releasing energy needed to synthesize ATP.
Both processes are carried out through reactions terintgrasi & organized  metabolism.
Metabolic products called metabolites. Branch of biology that studies the composition of metabolites as a whole at a developmental stage or on a body part called metabolomika

B. UNDERSTANDING FATS
Fats are biological molecules that do not dissolve in water butsoluble in organic solvents.
General nature of fat:
1. Usually obtained from animal
2. Have the shape of solid at room temperature
3. Composed of saturated fatty acids.
There are several functions of fat in them:
1. As constituent structure of cell membranes.
In this lipid acts as a barrier to cells and regulate the flow of materials.
2. As energy reserves
Fat is stored as adipose tissue.
3. Hormon and vitamins
Hormones regulate communication between cells, while vitamin helps the regulation of biological processes.


Types of fat
There are several types of fats are:
1. Acid fat consists of saturated fatty acids and unsaturated fatty acids
2. Glyceride, consisting of neutral glyceride and fosfogliserida
3. Fat complex, composed of lipoprotein and glycolipid
4. Non glyceride, consist of sfingolipid, steroids and night.

Fatty acid
Fatty acids are monocarboxylic acids of chain fatty acids common long. The formula is: CH3 (CH2) nCOOH or CnH2n +1- COOH. Distance size of the fatty acid is up to holdroom C24 C12.

There are two kinds of fatty acids, namely:
1. Acid saturated fat (saturated fatty acids) fatty acids have no double bonds.
2. Acid give the unsaturated fats (unsaturated fatty acids) fatty acids have one or more bond order.

Some examples of fatty acid structur
1. Gliserida neutral (neutral fat)
Is neutral fat glyceride esters of fatty acids with glycerol. The basic function of neutral glyceride is as energy savings (in the form of fat or oil). Each glycerol may bind to the 1, 2 or 3 fatty acids are not necessarily the same. If glycerol binds to a fatty acid called monoglycerides, if it binds to two known fatty acid diglycerides and if bonded to 3 fatty acids called triglycerides. Triglycerides are important energy reserves of lipid sources.
2. Fosfogliserida (phospholipids)
Lipids may contain phosphate groups. Fat modified when phosphate replacing one fatty acid chain.
Fosfogliserida usage is:
1.Sebagai composition of cell membranes
2. As with emulsion agent
3. Lipid complex
Lipid complex is a combination of lipids with other molecules.
An important example is the lipoprotein complex of lipids and glycolipid.

3. Lipoprotein
Lipoprotein is a combination of lipid with protein
There are 4 major classes of plasma lipoproteins, each composed of several types of lipids, namely:
Comparison of the composition making up four major classes of lipoprotein
1.Kilomikron
Chylomicrons serves as a means of transport triglycerides from the intestine into other tissues, except kidney
2. VLDL (very low - density lypoproteins)
Bind VLDL triglycerides in the liver and transported to fat tissue
3. LDL (low - density lypoproteins)
LDL carries cholesterol to peripheral tissues
4. HDL (high - density lypoproteins)
Plasma HDL cholesterol binding and transport cholesterol to the liver.

C. UNDERSTANDING THE LIPID METABOLISM (LIPID)
Lipid metabolism include oxidation of fatty acids, fatty acid synthesis, cholesterol synthesis, and lipid transport.
We get fat as its main energy source is of neutral lipids, namely triglycerides (esters of glycerol with 3 fatty acids). In summary, the results of the digestion of lipids are fatty acids and glycerol, other than that there is also still a monogliserid. Because soluble in water, glycerol enter the portal circulation (portal vein) to the liver. Acid-short-chain fatty acids can also be via this route.
Miselus structure. Polar parts are on the outside, while non-polar part is on the inside.


Most of the fatty acids and monoglycerides because it does not dissolve in water, then transported by miselus (in great shape called emulsions) and released into the intestinal epithelial cells (enterosit). In this cell fatty acids and monoglycerides soon formed into triglycerides (lipids) and assembly-shaped bubble called chylomicrons. Furthermore, chylomicrons are transported through the lymph vessels and lead to the vena cava, thus united by blood circulation. Chylomicrons are then transported to the liver and adipose tissue.




The structure of chylomicrons. Consider the function as a carrier triglyceride chylomicrons
Deposits of triglycerides in adipose tissue cell cytoplas
In the liver cells and adipose tissue, chylomicrons immediately broken down into fatty acids and glycerol. Furthermore, fatty acids and glycerol, the deposit was formed back into triglycerides. Triglyceride formation process is called esterification. At times when we need energy from lipids, triglycerides broken down into fatty acids and glycerol, to be transported into the cells to oxidized into energy. Solving process is called lipolysis of fat tissue. Fatty acids are transported by albumin to tissues that need and referred to as free fatty acids (free fatty acids / FFA).
In summary, the final result from the breakdown of lipids from food is a fatty acid and glycerol. If the source has sufficient energy from carbohydrates, the fatty acids having esterified with glycerol ester that is formed into triglycerides as a long-term energy reserves. If at any time no available source of energy from carbohydrates then oxidized fatty acids, both fatty acids from the diet or if you have to break down triglycerides reserve network. Triglyceride-solving process is called lipolysis.
Fatty acid oxidation process called beta oxidation and produces acetyl CoA. Furthermore, as acetyl CoA from the metabolism of carbohydrates and protein, acetyl CoA from even this point will enter into the citric acid cycle to produce energy. On the other hand, if demand is sufficient energy, can undergo lipogenesis acetyl CoA into fatty acid and can then be stored as triglycerides.
Some non-glyceride lipid synthesized from acetyl CoA. Acetyl CoA experience kolesterogenesis into cholesterol. Furthermore, cholesterol had formed steroid steroidogenesis. Acetyl CoA as a result of oxidation of fatty acids also have the potential to produce ketone bodies (aseto acetate, hydroxy butyrate and acetone). This process is called ketogenesis. Ketone bodies can cause acid-base balance disorder called metabolic acidosis. This condition can cause death.



















D. FIGURE LIPID METABOLISM



Lipid metabolism include oxidation of fatty acids, fatty acid synthesis, cholesterol synthesis, and lipid transport.






a. Oksidasi beta Fatty Acids
Takes place in mitochondria, resulting in a lot of ATP. Before oxidized, in the cytosol, activated fatty acids into acetyl-CoA used the fatty acid CoA acetyl-CoA ATP to AMP PPi. Acetyl-CoA then transported into the mitochondrial matrix in the form of bonded with karnitin (acyl-carnitine). In the matrix carnitine is released and the formed acetyl-CoA again. On oxidation, each times 2 C atoms liberated in the form of acetyl-CoA, starting from the carboxyl end of the generated NADH & FADH2. Oxidation occurs at C-beta (C to-3 atom of the carboxyl end), so-called beta oxidation. From Fatty Acid Beta oxidation process generated: acetyl-CoA, FADH and NADH. Futhermore acetyl-CoA is oxidized to CO2 in the TCA to produce ATP and NADH and FADH2 more.

b. Sintesis Fatty Acid
The main reactions that were most responsible is transasetilasi consists of the process of condensation, reduction, dehydration, and reduced again. Regulation of fatty acid synthesis, is regulated by Allosterik namely: stimulated by citrate, diinhibition by palmitoil CoA, the high beta-oxidation or esterification process to limit the number of TG. Fatty acid synthesis induced by insulin and glucagon repressed.
Insulin in the process of this synthesis function: (1) stimulate LPL by increasing the uptake of fatty acids from chylomicrons and VLDL, (2) stimulating glycolysis by increasing the synthesis of glycerol phosphate, (3) improve the process of esterification, (4) induces the phosphatase to menginaktif HSL HSL; (5) TG storage (net effect). At the time of famine or activity, the hormone glucagon and epinephrine activate adenilil cyclase to increase cAMP, activate proteyn cynase A, HSL activation resulting in the mobilization of TG (net affect) and fatty acids that increase. Synthesis of ketone bodies in fat occurs during starvation and heavy activity because of the higher production of fatty acids, HSL activity is high. The high fatty acid used as the energy produced in the liver fatty acid oxidation KB of 7 kcal / g.
Lipids are not soluble in the blood that is necessary to establish a special transport. Free fatty acids transported as bound to albumin. TAG, PL and cholesterol is transported as particles along with a protein called lipoproteins. In the form of lipoprotein, cholesterol and other lipid transported to the network. Lipids used are oxidized, stored, or to the process of synthesis. There are 4 channels of lipid transport, namely: (1) acid fat from adipose tissue to other networks (with albumin), (2) lipid of food from the intestine into other tissues (chylomicrons), (3) lipids that are synthesized in the body (endogenous) from the liver to other tissues (VLDL, LDL); ( 4) reverse cholesterol transport from tissues to the liver for exstracthepatik excreted through the bile (HDL).
Lipoprotein structure composed of TAG and cholesterol ester middle / outside the hydrophobic core coated by phospholipids and free cholesterol with proteins (called apolipoprotein, apoprotein). The more protein content, the greater density lipoprotein, based on its density is divided into: HDL, (IDL), LDL, VLDL, and chylomicrons. Lipoprotein destruction begins with the binding to receptors on the cell surface (endocytosis), followed by hydrolysis by lysosomes into its components. Chylomicrons transporting lipids absorbed from the intestine. VLDL (pre-beta lipoprotein) carries out the TAG of the liver. LDL (beta lipoprotein) derived from VLDL catabolism. HDL (alpha lipoprotein) to transport cholesterol to the liver tissue extracthepatik. TAG is a major lipid in chylomicrons and VLDL, while cholesterol and phospholipids in LDL and HDL.
Chylomicrons are the largest lipoprotein and the lightest as rich in TAG. Chylomicrons synthesized in intestinal epithelial cells, transport of lipids in foods is absorbed from the intestine into the lymph vessels, subsequent to the circulation of blood. 80-90% of TAG in chylomicrons taken enzym lypoprotein network with the aid of lipase (LPL) on capillary endothelial cell networks. After losing TAG chylomicrons into cholesterol-rich chylomicrons Remnant then binds to receptors on liver conduct endocytosis and degradation by lysosomes into components - components.
VLDL is formed in the liver, transport the TAG and cholesterol synthesis in the liver (endogenous) to another network (muscle, adipose). TAG components mainly synthesized from carbohydrates in food, also from excessive fat intake. Furthermore, as VLDL TAG packaged together with cholesterol, phospholipids and proteins to the circulation.
Like chylomicrons, VLDL is metabolized by LPL in the endothelial capillaries. TAG hydrolysed by LPL. Free fatty acids taken tissue (muscle, adipose) and then oxidized for energy / esterified back for storage. In state after meals, excessive fatty acid is taken to be stored as adipose tissue TAG. After the loss of TAG, VLDL turned into VLDL Remnant. 50% is taken care by way of endocytosis through binding to the receptor. The rest became IDL after losing more TAG and phospholipids, so that LDL rich in free cholesterol and esters: 60% is taken care by way of endocytosis, 40% taken extracthepatik network in the same way then degraded by lysosomes enzymes so that cholesterol is released as free cholesterol to inkoporasi to the membrane, the synthesis of steroid hormones or vitamin D, or esterified for storage. LDL cholesterol is a source for networking extracthepatik. When large excess LDL, LDL uptake system would be saturated so that excess LDL can be taken by macrophages because macrophages have a receptor called the scavenger lipoprotein receptor.
HDL, its main function of transporting excess cholesterol from peripheral tissues to the liver to process called reverse cholesterol transport. Free cholesterol from peripheral tissues / other lipoprotein cholesterol is converted into ester (enzyme lecithin-cholesterol acyl transferase, LCAT) and then transported to the liver and excreted into bile in the form of cholesterol as well as acid or bile salts. High levels of HDL in the blood is vaskuloprotektif.
Cholesterol is classified as lipids, have siklopentanohidrofenantren core. Cholesterol is present in the network, among others, as a structural component of membranes. In the plasma as lipoproteins, in free form or be given by fatty acids (cholesterol esters). Cholesterol serves as a component of cell membranes and precursors of steroid hormones (corticosteroids, sex hormones, etc.), acid or bile salts, vitamin D. Cholesterol contributes to the pathogenesis of atherosclerotic arteries causing cerebrovascular disease, coronary and peripheral.

c. Sintesis cholesterol
Mainly in the liver and the intestines. All its atoms C (27) derived from acetyl-CoA that can be derived from oxidation of carbohydrates, lipids, and amino acids. This process is derived from oxidation of carbohydrates, lipids and amino acids. Cholesterol synthesis takes place in the cytosol in 4 stages, with the enzyme HMG-CoA reductase as an (enzyme regulator). (1) Synthesis mevalonat, of acetyl-CoA: 2 mol acetyl-CoA condense into asetoasetil-CoA and then condensation with acetyl-CoA third form of beta-beta-OH metilglutaril-CoA (HMG - CoA) by the enzyme HMG - CoA synthase, reduced become mevalonat, enzyme HMG - CoA reductase (enzyme regulator). (2) Conversion into 2 isopren mevalonat active (5 C atoms). (3) Condensation of 6 active isoprene into skualen (30 atoms C). (4) Changes in skualen, lanosterol, steroid nucleus containing 4 ring hexagon.

d.Transport cholesterol
Transport of cholesterol in the form of lipoproteins, chylomicrons transport cholesterol from the intestine (derived from food) to the liver. VLDL, LDL, carry cholesterol from the liver to the network. Cholesterol is excreted into the bile in the form of cholesterol or acid / bile salts into the stool. Most acid / bile salt enterohepatic circulation experience. Get tissue cells synthesize cholesterol by itself (endogenous) or from LDL (exogenous). Hypercholesterolemia (elevated LDL cholesterol) is a risk factor for atherosclerosis and its complications occur namely coronary heart disease (CHD), acute myocardial infarction, stroke, etc. Coronary atherosclerosis related to cholesterol ratio of LDL: HDL plasma high.