Jaundice

Jaundice

Jaundice is not a disease but rather a sign that can occur in many different diseases. Jaundice is the yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of the chemical bilirubin. The color of the skin and sclerae vary depending on the level of bilirubin. When the bilirubin level is mildly elevated, they are yellowish. When the bilirubin level is high, they tend to be brown.

What causes jaundice?

Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed. Hemoglobin, the iron-containing chemical in red blood cells that carries oxygen, is released from the destroyed red blood cells after the iron it contains is removed. The chemical that remains in the blood after the iron is removed becomes bilirubin.

The liver has many functions. One of the liver's functions is to produce and secrete bile into the intestines to help digest dietary fat. Another is to remove toxic chemicals or waste products from the blood, and bilirubin is a waste product. The liver removes bilirubin from the blood. After the bilirubin has entered the liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its brown color.) Conjugated bilirubin is distinguished from the bilirubin that is released from the red blood cells and not yet removed from the blood which is termed unconjugated bilirubin.

Jaundice occurs when there is 1) too much bilirubin being produced for the liver to remove from the blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their red blood cells that releases large amounts of bilirubin into the blood), 2) a defect in the liver that prevents bilirubin from being removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver into the intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis does not always result in jaundice.

What problems does jaundice cause? 



Jaundice or cholestasis, by themselves, causes few problems (except in the newborn, and jaundice in the newborn is different than most other types of jaundice, as discussed later.) Jaundice can turn the skin and sclerae yellow. In addition, stool can become light in color, even clay-colored because of the absence of bilirubin that normally gives stool its brown color. The urine may turn dark or brownish in color. This occurs when the bilirubin that is building up in the blood begins to be excreted from the body in the urine. Just as in feces, the bilirubin turns the urine brown. 



Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus. The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to scratch their skin "raw," have trouble sleeping, and, rarely, even to commit suicide. 

It is the disease causing the jaundice that causes most problems associated with jaundice. Specifically, if the jaundice is due to liver disease, the patient may have symptoms or signs of liver disease or cirrhosis. 

If the jaundice is caused by blockage of the bile ducts, no bile enters the intestine. Bile is necessary for digesting fat in the intestine and releasing vitamins from within it so that the vitamins can be absorbed into the body. Therefore, blockage of the flow of bile can lead to deficiencies of certain vitamins. For example, there may be a deficiency of vitamin K that prevents proteins that are needed for normal clotting of blood to be made by the liver, and, as a result, uncontrolled bleeding may occur. 

What diseases cause jaundice? 

Increased production of bilirubin
There are several uncommon conditions that give rise to over-production of bilirubin. These conditions include: 1) rapid destruction of red blood cells (referred to as hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the tissues).

Acute inflammation of the liver
Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity.

Chronic liver diseases
Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice. Common examples include chronic hepatitis B and C, alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

Infiltrative diseases of the liver
Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that don't belong there. The most common example would be metastatic cancer to the liver, usually from cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson's disease).

Inflammation of the bile ducts
Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice. 

Blockage of the bile ducts
The most common causes of blockage of the bile ducts are gallstones and pancreatic cancer. Less common causes include cancers of the liver and bile ducts.

Drugs
Many drugs can cause jaundice and/or cholestasis. Some drugs can cause liver inflammation (hepatitis) similar to viral hepatitis. Other drugs can cause inflammation of the bile ducts, resulting in cholestasis and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver and bile ducts that are responsible for the formation and secretion of bile to the intestine. As a result, the constituents of bile, including bilirubin, are retained in the body. 

Genetic disorders
There are several rare genetic disorders present from birth that give rise to jaundice. Crigler-Najjar syndrome is caused by a defect in the conjugation of bilirubin in the liver due to a reduction or absence of the enzyme responsible for conjugating the glucuronic acid to bilirubin. Dubin-Johnson and Rotor's syndromes are caused by abnormal secretion of bilirubin into bile.

The only common genetic disorder that may cause jaundice is Gilbert's syndrome which affects approximately 7% of the population. Gilbert's syndrome is caused by a mild reduction in the activity of the enzyme responsible for conjugating the glucuronic acid to bilirubin.

Developmental abnormalities of bile ducts
There are rare instances in which the bile ducts do not develop normally and the flow of bile is interrupted. Jaundice frequently occurs. These diseases usually are present from birth though some of them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts) are an example of such a developmental abnormality. Another example is Caroli's disease.

Jaundice of pregnancy
Most of the diseases discussed previously can affect women during pregnancy, but there are some additional causes of jaundice that are unique to pregnancy.

Pre-eclampsia. Pre-eclampsia, previously called toxemia of pregnancy, is a disease that occurs during the second half of pregnancy and involves several systems within the body, including the liver. It may result in high blood pressure, fluid retention, and damage to the kidneys as well as anemia and reduced numbers of platelets due to destruction of red blood cells and platelets. It often causes problems for the fetus. 

Acute fatty liver of pregnancy. Acute fatty liver of pregnancy (AFLP) is a very serious complication of pregnancy of unclear cause that often is associated with pre-eclampsia. It occurs late in pregnancy and results in failure of the liver. It can almost always be reversed by immediate delivery of the fetus. 

How is the cause of jaundice diagnosed?

Many tests are available for determining the cause of jaundice, but the history and physical examination are important as well.

History
The history can suggest possible reasons for the jaundice. For example, heavy use of alcohol suggests alcoholic liver disease, whereas use of illegal, injectable drugs suggests viral hepatitis. Recent initiation of a new drug suggests drug-induced jaundice. Episodes of abdominal pain associated with jaundice suggests blockage of the bile ducts usually by gallstones.

Physical examination
The most important part of the physical examination in a patient who is jaundiced is examination of the abdomen. Masses (tumors) in the abdomen suggest cancer infiltrating the liver (metastatic cancer) as the cause of the jaundice. An enlarged, firm liver suggests cirrhosis. A rock-hard, nodular liver suggests cancer within the liver.

Blood tests
Measurement of bilirubin can be helpful in determining the causes of jaundice. Markedly greater elevations of unconjugated bilirubin relative to elevations of conjugated bilirubin in the blood suggest hemolysis (destruction of red blood cells). Marked elevations of liver tests (aspartate amino transferase or AST and alanine amino transferase or ALT) suggest inflammation of the liver (such as viral hepatitis). Elevations of other liver tests, e.g., alkaline phosphatase, suggest diseases or obstruction of the bile ducts.

Ultrasonography
Ultrasonography is a simple, safe, and readily-available test that uses sound waves to examine the organs within the abdomen. Ultrasound examination of the abdomen may disclose gallstones, tumors in the liver or the pancreas, and dilated bile ducts due to obstruction (by gallstones or tumor).

Computerized tomography (CT or CAT scans)
Computerized tomography or CT scans are scans that use x-rays to examine the soft tissues of the abdomen. They are particularly good for identifying tumors in the liver and the pancreas and dilated bile ducts, though they are not as good as ultrasonography for identifying gallstones.

Magnetic resonance imaging (MRI)
Magnetic Resonance Imaging scans are scans that utilize magnetization of the body to examine the soft tissues of the abdomen. Like CT scans, they are good for identifying tumors and studying bile ducts. MRI scans can be modified to visualize the bile ducts better than CT scans (a procedure referred to as MR cholangiography), and, therefore, are better than CT for identifying the cause and location of bile duct obstruction.

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound

Endoscopic retrograde cholangiopancreatography (ERCP) provides the best means for examining the bile duct. For ERCP an endoscope is swallowed by the patient after he or she has been sedated. The endoscope is a flexible, fiberoptic tube approximately four feet in length with a light and camera on its tip. The tip of the endoscope is passed down the esophagus, through the stomach, and into the duodenum where the main bile duct enters the intestine. A thin tube then is passed through the endoscope and into the bile duct, and the duct is filled with x-ray contrast solution. An x-ray is taken that clearly demonstrates the contrast-filled bile ducts. ERCP is particularly good at demonstrating the cause and location of obstruction within the bile ducts.
Ultrasonography can be combined with ERCP by using a specialized endoscope capable of doing ultrasound scanning. Endoscopic ultrasound is excellent for diagnosing small gallstones in the gallbladder and bile ducts that can be missed by other diagnostic methods such as ultrasound, CT, and MRI. It also is the best means of examining the pancreas for tumors and can facilitate biopsy through the endoscope of tumors within the pancreas.

Liver biopsy
Biopsy of the liver provides a small piece of tissue from the liver for examination under the microscope. The biopsy most commonly is done with a long needle after local injection of the skin of the abdomen overlying the liver with anesthetic. The needle passes through the skin and into the liver, cutting off a small piece of liver tissue. When the needle is withdrawn, the piece of liver comes with it. Liver biopsy is particularly good for diagnosing inflammation of the liver and bile ducts, cirrhosis, cancer, and fatty liver.

How is jaundice treated?

With the exception of the treatments for specific causes of jaundice mentioned previously, the treatment of jaundice usually requires a diagnosis of the specific cause of the jaundice and treatment directed at the specific cause, e.g., removal of a gallstone blocking the bile duct.

Vitamin A & Acne

Vitamin A & Acne

Have you heard of (or tried) the popular prescription acne medications Accutane or Retin-A?  Accutane is a powerful oral medication that is prescribed for mild to moderate acne cases, and Retin-A is the same kind of medication, just in topical form.

So what is about these two medications that work so well to heal acne??  Its vitamin A!

Plain and simply - Accutane is nearly identical to an EXTREMELY high dose of vitamin A. I'm talking more than double, triple, and quadruple times the amount of suggested vitamin A daily intake.  Suggested IU for vitamin A is 4,000 - but to take enough to equal the amount that is in Accutane would be 250,000 IU.

The topical medication Retin-A works the same way, except in a cream.  The main active ingredient is vitamin A! Hence the Retin "A."

So how does vitamin A work to treat acne? Well, it heals the skin. Acne is like a sore, it needs lots of vitamins in order to heal itself. Many people claim that high doses of vitamin-a (100,000 IU or more) taken daily for just ONE week will show dramatic results. Reduced redness and break-outs are common within the first month of taking it, and clear, healthy skin is usually achieved by the second month.

Side effects of high doses of the vitamin include dry skin (very common), headache, and occasionally hair loss.

Danger: Vitamin A is not water soluble. This means that when taken in excess, the extra vitamin is not excreted but rather is stored in fat tissues. An immense build-up can be dangerous, if high doses are taken for a year or more. More importantly, too much vitamin A can cause birth defects. Women who are pregnant or planning to get pregnant should NEVER take vitamin A supplements over 4,000 IU.

Be very careful if you choose to take the Vitamin-A route to clear skin! It's best to consult with your doctor before taking large amounts of any kind of supplement.

Vitamin E,What it Does and Why it is So Important to Get an Adequate Supply

Vitamin E; What it Does? and Why it is So Important to Get an Adequate Supply?

If you want to remain in healthy condition, then you need to be in the habit of eating proper foods. Further to this, you also need to get the proper amount of vitamins and minerals. If for some reason, you are not getting enough of these nutrients, you may require vitamin supplements in order to function at an optimal level. You should not overlook the importance of vitamins. Vitamin E is one of the 13 vitamins which our body absolutely requires so it will be helpful if we understand exactly what it does to our body. Basically, if we know how a particular supplement affects our body from a physiological point of view, we are more likely to take that supplement when it is needed.

A few of the vitamins which are required by our body cells are known as fat soluble and vitamin E falls into this class. Now any fat soluble vitamin will stay in the body for an extended period of time, whereas water soluble vitamins cannot be stored within. Since vitamin E has the ability to be stored within our body, we do not have to consume it every day. In spite of this, we still need to get an adequate supply over the course of time, either from the food we eat or by taking extra supplements.

Vitamin E more than anything else acts as an antioxidant. Antioxidants act as caretakers for the inner workings of our body. More specifically, antioxidants protect our body cells from the damage which would otherwise occur as a result of free radicals. These free radicals originate from toxins or pollution and once they enter our body, they are very unstable and dangerous to our health. Because cells are the building blocks for our organs, it is important to have an adequate supply of the right antioxidants in order to remain in top health. These antioxidants are also known to slow down the aging process. Vitamin E also has another very important function in that it allows the body cells to utilize vitamin K. Since vitamin K helps with blood clotting, this is a very important feature.

Generally speaking if you are eating a healthy diet, you should be getting enough vitamin E from this alone. Some of the foods which contain a lot of vitamin E are: olives, vegetable oil, margarine, corn, wheat germ, asparagus, mixed nuts, spinach and other leafy green vegetables. Make sure that you scrutinize the labels on any packaged or canned foods which you eat: These labels will list the nutritional ingredients contained within. Another name for vitamin E is tocopherol, so keep an eye out for this when you are reading labels.

Having a slight deficiency in E vitamins is usually not that big of a problem, but you will not get the benefits of the antioxidant features. Even taking too much is generally not too problematic as long as it is not for too long of an extended time period. In a few isolated cases, individuals have reported getting headaches from extended overuse of vitamin E. Be cautious if you are using a multi-vitamin supplement as too many of some of the other vitamins can be bad for you over the long term. If you are planning to take some vitamin supplements, you should really check in with your family doctor first and he or she can give you some sound advice on how much you should actually be taking.

The Ugly truth About Vitamin D Deficiency

The Ugly truth About Vitamin D Deficiency 

 

Vitamin D deficiency is the newest of many problems that are being pointed out as the reason for numerous maladies like heart condition to diabetes and even depression. There are numerous medical references and speculation in the medical community about the nature of the deficiency but only one thing is clear, Vitamin D deficiency is a problem that is still not fully clear even in the medical community.

Undoubtedly, a lot have been learned about vitamin D and its numerous variations. The medical community has learned that it may play a more vital role more than the health of the musculoskeletal health for which it has been widely known. Vitamin D has long been considered as an essential component for calcium metabolism. A comparison of low Vitamin D levels with various conditions has been recently cited but the association does not mean that Vitamin D is the root cause of the problem. There are numerous factors and their connection that play a major role in the whole disease process while some other factors may only be coincidences.

Even though experts are pushing for examining vitamin D levels and start treating low levels, they say that what is really important are a controlled study of large groups of individuals in the long term to see if the lack vitamin D really cause heart disease or any other condition which it is being blamed into. This is just a classic case of guilt by association without any solid proof. There are different examples in real life and the field of medicine where we immediately believe on recommendations that seemed believable only to find out later that is ineffective and lack substance.

Nutrient and vitamin supplements are one of the more vague divisions of science in terms of enough proof to justify the use of the product to customers. Vitamins are usually use for prevention of colds which sometimes do not work for some individuals. A lot of supposed vitamin deficiencies that can be solved by supplements, not by a balanced diet, have been unsuccessful for numerous reasons that people do not really understand.

Like the use of estrogen supplementation for women that are already in the postmenopausal stage as a protection for cardiovascular related diseases was an accepted promise for years. But when a thorough study was done, using estrogen supplements lacked any protective benefits and had some disadvantageous effects in some cases.

It is really difficult to take vitamin D from a diet consists of oily fish like a salmon because it have to be consumed in bulk. Constant exposure to sunlight also gives you vitamin D. But this effect is diminished on a person that has a heavily pigmented skin, on the elderly or in people who do not spend a lot of time outdoors.

Some foods also contain vitamin D like milk and cheese but the amounts that are present in these foods are not enough to satisfy the needs of an average person. The risk of toxicity is low but possible so it is very important for people to follow the recommended dosage for vitamin D that have been recommended by experts on this field.

Symptoms for vitamin D toxicity include weakness, thirst, excessive urination and itching. Keeping an eye on your vitamin D intake is simple enough aside from supplementation. But one has to think about the bigger picture: do you really benefit from it? Is it advisable to follow all of these things for something that may be good or bad for your body? You should always consult your doctor in order to monitor your Vitamin D intake.

Leucine

Leucine

Leucine is an essential amino acid which means that it is not produced by the body, thus it has to be taken as an important component of proteins particularly the amino acids L-isoleucine and L-valine through the food we eat.

L-Leucine is a major component of the buffer proteins ferritin, and astacin. Ferritin is a kind of protein found in cells that stores iron and releases it in a limited way. It is called a buffer protein because it protects the body when it is deficient in iron or when it has reached iron toxicity level.

Leucine is substantially used in the production of sterols or fat-like substances (most famous of which is cholesterol) in the liver, adipose and muscles tissues, but seven times more active in the muscle and adipose tissues than in the liver.

It is a perfect dietary supplement as evidenced in an experiment with laboratory rats which showed that it delayed the deterioration of muscle tissues by significantly increasing the production of muscle proteins.

Because of these properties, L-Leucine is highly recommended as a dietary supplement for athletes to increase their strength, power, and endurance. This property of L-leucine makes it an ideal supplement for those recuperating from major surgery or in cases where there is severe muscle pain and serious injury.

Leucine is believed to promote the growth of new muscles in the body due to its ability to increase production of muscle proteins thus making this the perfect supplement for body builders and athletes.

Leucine is also perfect for weight watchers. It has the ability to dissolve visceral fat, the kind of fact that is found in the deepest layer of the skin that does not respond to ordinary, uninvasive method of fat loss.

Leucine provides the body with energy it needs especially during intense athletic performance and other strenuous activities. This can be attributed to leucine's role in the production of fat-like substances called sterols in the adipose and muscle tissues. It prevents the deterioration of muscle tissues and the early onset of fatigue during exercise. It also regulates blood sugar levels, increases energy and stimulates the development of human growth hormones.

A high toxic level of L-Leucine can lead to Maple Syrup Urine Disease (MSUD), a disorder caused by the lack of the branched chain amino acid keto hydrogenase complex leading to the accumulation in the blood and urine of the proteins leucine, isoleucine and valine and their toxic by-products. An infant suffering from MSUD has a sweet smelling urine much like maple syrup, thus the name of the disease.

Foods rich in leucine include soy beans and cowpeas, beef and fish, eggs, chicken, lentils, cashew nuts and brown rice. Since leucine is not synthesized by the body, it is advisable that you eat lots of these foods or take dietary supplements to be able to optimize the full benefits of this important protein.

Valine; An Essential Amino Acid

Valine : An Essential Amino Acid

Valine is one of twenty commonly found amino acids found in nature.  Valine is a hydrophobic, nonpolar protein that is found in the interior of most proteins in muscles. The structure of valine includes three branched chain of methyl groups at one end. there are only tow other branched chain amino acids which are isoleucine and leucine. Valine is very important for muscle metabolism and the repair/growth of tissue. For muscle growth valine promotes protein production. It also helps with the balance of nitrogen in the body. Because of the branched chain it can be used as an energy source in muscles instead of glucose. It goes about this by suppressing protein catabolism and begins the process of gluconeogenesis. The branched chained amino acids can be an important fuel source for skeletal muscles when they are in periods of metabolic stress.

A German scientist by the name of Emil Fischer discovered Valine in the year 1901. She found out that Valine is an essential vitamin that can not be made by the body. Therefore, Valine must be ingested from one of the number of sources including dairy, meat, mushrooms and some peanuts. In the latest studies Valine has been proven to help people who are having muscle, mental, and emotional upsets. Also people with insomnia and nervousness have been given Valine doses. Another way that valine helps is in the synthesis of glucose in the liver during anaerobic activities. Valine is also used in biochemical, biophysical and crystallographic research.

A deficiency in valine results in a negative hydrogen balance in the body, deterioration of muscle function and mental health. Sometimes a deficiency can lead to maple syrup urine disease. This disease can ultimately cause damage to the brain during times of physical stress and mental retardation. This disease is most dangerous in young children, but has also been found in kids still in their childhood. As a person gets older the intensity of the disease becomes less. A regulated diet can help to accommodate those with this disease

Contributed By

Shahnawaz Mugheri

Batch 36

Chandka Medical College Larkana

Lipids

Lipids

Fig. Structures of some common lipids. These are a broad group of naturally occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The main biological functions of lipids include energy storage, as structural components of cell membranes, and as important signaling molecules.

Lipids may be broadly defined as hydrophobic or amphiphilic small molecules; the amphiphilic nature of some lipids allows them to form structures such as vesicles, liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits or "building blocks": ketoacyl and isoprene groups. Using this approach, lipids may be divided into eight categories: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids,saccharolipids and polyketides (derived from condensation of ketoacyl subunits); and sterol lipids and prenol lipids (derived from condensation of isoprene subunits).

Although the term lipid is sometimes used as a synonym for fats, fats are a subgroup of lipids calledtriglycerides. Lipids also encompass molecules such as fatty acids and their derivatives (including tri-,di-, and monoglycerides and phospholipids), as well as other sterol-containing metabolites such ascholesterol Although humans and other mammals use various biosynthetic pathways to both break down and synthesize lipids, some essential lipids cannot be made this way and must be obtained from the diet.

• Topics As Under Are
• Categories OF lipids
  • Fatty acyls
  • Glycerolipids
  • Glycerophospholipids
  • Sphingolipids
  • Sterol lipids
  • Prenol lipids
  • Saccharolipids
  • Polyketides
• Biological functions
  • Membranes
  • Energy storage
  • Signaling
  • Other functions
• Metabolism
  • Biosynthesis
  • Degradation
• Nutrition and health

Fatty acyls

Fatty acyls, a generic term for describing fatty acids, their conjugates and derivatives, are a diverse group of molecules synthesized by chain-elongation of an acetyl-CoA primer withmalonyl-CoA or methylmalonyl-CoA groups in a process called fatty acid synthesis. They are made of a hydrocarbon chain that terminates with a carboxylic acid group; this arrangement confers the molecule with a polar, hydrophilic end, and a nonpolar, hydrophobic end that is insoluble in water. The fatty acid structure is one of the most fundamental categories of biological lipids, and is commonly used as a building block of more structurally complex lipids. The carbon chain, typically between four to 24 carbons long, may be saturated or unsaturated, and may be attached to functional groups containing oxygen, halogens, nitrogen and sulfur. Where a double bond exists, there is the possibility of either a cis or trans geometric isomerism, which significantly affects the molecule's molecular configuration. Cis-double bonds cause the fatty acid chain to bend, an effect that is more pronounced the more double bonds there are in a chain. This in turn plays an important role in the structure and function of cell membranes. Most naturally occurring fatty acids are of the cis configuration, although the trans form does exist in some natural and partially hydrogenated fats and oils.

Examples of biologically important fatty acids are the eicosanoids, derived primarily from arachidonic acid and eicosapentaenoic acid, which include prostaglandins, leukotrienes, andthromboxanes. Other major lipid classes in the fatty acid category are the fatty esters and fatty amides. Fatty esters include important biochemical intermediates such as wax esters, fatty acid thioester coenzyme A derivatives, fatty acid thioester ACP derivatives and fatty acid carnitines. The fatty amides include N-acyl ethanolamines, such as the cannabinoidneurotransmitter anandamide.

Glycerolipids

Glycerolipids are composed mainly of mono-, di- and tri-substituted glycerols, the most well-known being the fatty acid esters of glycerol (triacylglycerols), also known astriglycerides. In these compounds, the three hydroxyl groups of glycerol are each esterified, usually by different fatty acids. Because they function as a food store, these lipids comprise the bulk of storage fat in animal tissues. The hydrolysis of the ester bonds of triacylglycerols and the release of glycerol and fatty acids from adipose tissue is called fat mobilization.

Additional subclasses of glycerolipids are represented by glycosylglycerols, which are characterized by the presence of one or more sugar residues attached to glycerol via a glycosidic linkage. Examples of structures in this category are the digalactosyldiacylglycerols found in plant membranes and seminolipid from mammalian sperm cells.

Glycerophospholipids

Glycerophospholipids, also referred to as phospholipids, are ubiquitous in nature and are key components of the lipid bilayer of cells, as well as being involved in metabolism and cell signaling. Neural tissue (including the brain) contains relatively high amounts of glycerophospholipids, and alterations in their composition has been implicated in various neurological disorders. Glycerophospholipids may be subdivided into distinct classes, based on the nature of the polar headgroup at the sn-3 position of the glycerol backbone in eukaryotes and eubacteria, or the sn-1 position in the case of archaebacteria.

Phosphatidylethanolamine

Examples of glycerophospholipids found in biological membranes are phosphatidylcholine (also known as PC, GPCho or lecithin),phosphatidylethanolamine (PE or GPEtn) and phosphatidylserine (PS or GPSer). In addition to serving as a primary component of cellular membranes and binding sites for intra- and intercellular proteins, some glycerophospholipids in eukaryotic cells, such as phosphatidylinositolsand phosphatidic acids are either precursors of, or are themselves, membrane-derived second messengers. Typically, one or both of these hydroxyl groups are acylated with long-chain fatty acids, but there are also alkyl-linked and 1Z-alkenyl-linked (plasmalogen) glycerophospholipids, as well as dialkylether variants in archaebacteria.

Sphingolipids

Sphingolipids are a complex family of compounds that share a common structural feature, a sphingoid base backbone that is synthesized de novo from the amino acid serine and a long-chain fatty acyl CoA, then converted into ceramides, phosphosphingolipids, glycosphingolipids and other compounds. The major sphingoid base of mammals is commonly referred to as sphingosine. Ceramides (N-acyl-sphingoid bases) are a major subclass of sphingoid base derivatives with an amide-linked fatty acid. The fatty acids are typically saturated or mono-unsaturated with chain lengths from 16 to 26 carbon atoms.

Sphingomyelin

The major phosphosphingolipids of mammals are sphingomyelins (ceramide phosphocholines), whereas insects contain mainly ceramide phosphoethanolamines and fungi have phytoceramide phosphoinositols and mannose-containing headgroups. The glycosphingolipids are a diverse family of molecules composed of one or more sugar residues linked via a glycosidic bond to the sphingoid base. Examples of these are the simple and complex glycosphingolipids such as cerebrosides and gangliosides.

Sterol lipids

Sterol lipids, such as cholesterol and its derivatives, are an important component of membrane lipids, along with the glycerophospholipids and sphingomyelins. The steroids, all derived from the same fused four-ring core structure, have different biological roles as hormones and signaling molecules. The eighteen-carbon (C18) steroids include the estrogen family whereas the C19 steroids comprise the androgens such as testosterone and androsterone. The C21 subclass includes the progestogens as well as the glucocorticoids andmineralocorticoids. The secosteroids, comprising various forms of vitamin D, are characterized by cleavage of the B ring of the core structure. Other examples of sterols are the bile acids and their conjugates, which in mammals are oxidized derivatives of cholesterol and are synthesized in the liver. The plant equivalents are the phytosterols, such as β-sitosterol,stigmasterol, and brassicasterol; the latter compound is also used as a biomarker for algal growth. The predominant sterol in fungal cell membranes is ergosterol.

Prenol lipids

Prenol lipids are synthesized from the 5-carbon precursors isopentenyl diphosphate and dimethylallyl diphosphate that are produced mainly via the mevalonic acid (MVA) pathway.The simple isoprenoids (linear alcohols, diphosphates, etc.) are formed by the successive addition of C5 units, and are classified according to number of these terpene units. Structures containing greater than 40 carbons are known as polyterpenes. Carotenoids are important simple isoprenoids that function as antioxidants and as precursors of vitamin A. Another biologically important class of molecules is exemplified by the quinones and hydroquinones, which contain an isoprenoid tail attached to a quinonoid core of non-isoprenoid origin.Vitamin E and vitamin K, as well as the ubiquinones, are examples of this class. Prokaryotes synthesize polyprenols (called bactoprenols) in which the terminal isoprenoid unit attached to oxygen remains unsaturated, whereas in animal polyprenols (dolichols) the terminal isoprenoid is reduced.

Saccharolipids

Structure of the saccharolipid Kdo₂-Lipid A.Glucosamine residues in blue, Kdo residues in red, acyl chains in black and phosphate groups in green.

Saccharolipids describe compounds in which fatty acids are linked directly to a sugar backbone, forming structures that are compatible with membrane bilayers. In the saccharolipids, a monosaccharide substitutes for the glycerol backbone present in glycerolipids and glycerophospholipids. The most familiar saccharolipids are the acylated glucosamine precursors of the Lipid Acomponent of the lipopolysaccharides in Gram-negative bacteria. Typical lipid A molecules are disaccharides of glucosamine, which are derivatized with as many as seven fatty-acyl chains. The minimal lipopolysaccharide required for growth in E. coli is Kdo₂-Lipid A, a hexa-acylated disaccharide of glucosamine that is glycosylated with two 3-deoxy-D-manno-octulosonic acid (Kdo) residues.

Polyketides

Polyketides are synthesized by polymerization of acetyl and propionyl subunits by classic enzymes as well as iterative and multimodular enzymes that share mechanistic features with the fatty acid synthases. They comprise a large number ofsecondary metabolites and natural products from animal, plant, bacterial, fungal and marine sources, and have great structural diversity. Many polyketides are cyclic molecules whose backbones are often further modified by glycosylation,methylation, hydroxylation, oxidation, and/or other processes. Many commonly used anti-microbial, anti-parasitic, and anti-cancer agents are polyketides or polyketide derivatives, such as erythromycins, tetracyclines, avermectins, and antitumorepothilones.

Biological functions

Membranes

Eukaryotic cells are compartmentalized into membrane-bound organelles which carry out different biological functions. The glycerophospholipids are the main structural component ofbiological membranes, such as the cellular plasma membrane and the intracellular membranes of organelles; in animal cells the plasma membrane physically separates the intracellularcomponents from the extracellular environment. The glycerophospholipids are amphipathic molecules (containing both hydrophobic and hydrophilic regions) that contain a glycerol core linked to two fatty acid-derived "tails" by ester linkages and to one "head" group by a phosphate ester linkage. While glycerophospholipids are the major component of biological membranes, other non-glyceride lipid components such as sphingomyelin and sterols (mainly cholesterol in animal cell membranes) are also found in biological membranes. In plants and algae, the galactosyldiacylglycerols, and sulfoquinovosyldiacylglycerol, which lack a phosphate group, are important components of membranes of chloroplasts and related organelles and are the most abundant lipids in photosynthetic tissues, including those of higher plants, algae and certain bacteria.

Bilayers have been found to exhibit high levels of birefringence which can be used to probe the degree of order (or disruption) within the bilayer using techniques such as dual polarisation interferometry

Self-organization of phospholipids: a sphericalliposome, a micelle and a lipid bilayer.

A biological membrane is a form of lipid bilayer. The formation of lipid bilayers is an energetically preferred process when theglycerophospholipids described above are in an aqueous environment. In an aqueous system, the polar heads of lipids align towards the polar, aqueous environment, while the hydrophobic tails minimize their contact with water and tend to cluster together, forming avesicle; depending on the concentration of the lipid, this biophysical interaction may result in the formation of micelles, liposomes, or lipid bilayers. Other aggregations are also observed and form part of the polymorphism of amphiphile (lipid) behavior. Phase behavior is an area of study within biophysics and is the subject of current academic research. Micelles and bilayers form in the polar medium by a process known as the hydrophobic effect. When dissolving a lipophilic or amphiphilic substance in a polar environment, the polar molecules (i.e., water in an aqueous solution) become more ordered around the dissolved lipophilic substance, since the polar molecules cannot form hydrogen bonds to the lipophilic areas of the amphiphile. So in an aqueous environment, the water molecules form an ordered "clathrate" cage around the dissolved lipophilic molecule.

Energy storage

Triacylglycerols, stored in adipose tissue, are a major form of energy storage in animals. The adipocyte, or fat cell, is designed for continuous synthesis and breakdown of triacylglycerols, with breakdown controlled mainly by the activation of hormone-sensitive enzyme lipase. The complete oxidation of fatty acids provides high caloric content, about 9 kcal/g, compared with 4 kcal/g for the breakdown ofcarbohydrates and proteins. Migratory birds that must fly long distances without eating use stored energy of triacylglycerols to fuel their flights.

Signaling

In recent years, evidence has emerged showing that lipid signaling is a vital part of the cell signaling. Lipid signaling may occur via activation of G protein-coupled or nuclear receptors, and members of several different lipid categories have been identified as signaling molecules and cellular messengers. These include sphingosine-1-phosphate, a sphingolipid derived from ceramide that is a potent messenger molecule involved in regulating calcium mobilization, cell growth, and apoptosis;diacylglycerol (DAG) and the phosphatidylinositol phosphates (PIPs), involved in calcium-mediated activation of protein kinase C; the prostaglandins, which are one type of fatty-acid derived eicosanoid involved in inflammation and immunity; the steroid hormones such as estrogen, testosterone and cortisol, which modulate a host of functions such as reproduction, metabolism and blood pressure; and the oxysterols such as 25-hydroxy-cholesterol that are liver X receptor agonists.

Other functions

The "fat-soluble" vitamins (A, D, E and K) – which are isoprene-based lipids – are essential nutrients stored in the liver and fatty tissues, with a diverse range of functions. Acyl-carnitinesare involved in the transport and metabolism of fatty acids in and out of mitochondria, where they undergo beta oxidation. Polyprenols and their phosphorylated derivatives also play important transport roles, in this case the transport of oligosaccharides across membranes. Polyprenol phosphate sugars and polyprenol diphosphate sugars function in extra-cytoplasmic glycosylation reactions, in extracellular polysaccharide biosynthesis (for instance, peptidoglycan polymerization in bacteria), and in eukaryotic protein N-glycosylation.Cardiolipins are a subclass of glycerophospholipids containing four acyl chains and three glycerol groups that are particularly abundant in the inner mitochondrial membrane. They are believed to activate enzymes involved with oxidative phosphorylation.

Metabolism:The major dietary lipids for humans and other animals are animal and plant triglycerides, sterols, and membrane phospholipids. The process of lipid metabolism synthesizes and degrades the lipid stores and produces the structural and functional lipids characteristic of individual tissues.

Biosynthesis

In animals, when there is an oversupply of dietary carbohydrate, the excess carbohydrate is converted to triacylglycerol. This involves the synthesis of fatty acids from acetyl-CoA and the esterification of fatty acids in the production of triacylglycerol, a process called lipogenesis. Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units. The acyl chains in the fatty acids are extended by a cycle of reactions that add the acetyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group. The enzymes of fatty acid biosynthesis are divided into two groups, in animals and fungi all these fatty acid synthase reactions are carried out by a single multifunctional protein, while in plant plastids and bacteria separate enzymes perform each step in the pathway. The fatty acids may be subsequently converted to triacylglycerols that are packaged in lipoproteins and secreted from the liver.

The synthesis of unsaturated fatty acids involves a desaturation reaction, whereby a double bond is introduced into the fatty acyl chain. For example, in humans, the desaturation ofstearic acid by stearoyl-CoA desaturase-1 produces oleic acid. The doubly unsaturated fatty acid linoleic acid as well as the triply unsaturated α-linolenic acid cannot be synthesized in mammalian tissues, and are therefore essential fatty acids and must be obtained from the diet.

Triacylglycerol synthesis takes place in the endoplasmic reticulum by metabolic pathways in which acyl groups in fatty acyl-CoAs are transferred to the hydroxyl groups of glycerol-3-phosphate and diacylglycerol.

Terpenes and isoprenoids, including the carotenoids, are made by the assembly and modification of isoprene units donated from the reactive precursors isopentenyl pyrophosphate anddimethylallyl pyrophosphate. These precursors can be made in different ways. In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non-mevalonate pathway uses pyruvate and glyceraldehyde 3-phosphate as substrates. One important reaction that uses these activated isoprene donors is steroid biosynthesis. Here, the isoprene units are joined together to make squalene and then folded up and formed into a set of rings to make lanosterol.Lanosterol can then be converted into other steroids such as cholesterol and ergosterol.

Degradation

Beta oxidation is the metabolic process by which fatty acids are broken down in the mitochondria and/or in peroxisomes to generate acetyl-CoA. For the most part, fatty acids are oxidized by a mechanism that is similar to, but not identical with, a reversal of the process of fatty acid synthesis. That is, two-carbon fragments are removed sequentially from the carboxyl end of the acid after steps of dehydrogenation, hydration, and oxidation to form a beta-keto acid, which is split by thiolysis. The acetyl-CoA is then ultimately converted intoATP, CO₂, and H₂O using the citric acid cycle and the electron transport chain.

Hence the Krebs Cycle can start at acetyl-CoA when fat is being broken down for energy if there is little or no glucose available.

The energy yield of the complete oxidation of the fatty acid palmitate is 106 ATP. Unsaturated and odd-chain fatty acids require additional enzymatic steps for degradation.

Nutrition and health: 

Most of the lipid found in food is in the form of triacylglycerols, cholesterol and phospholipids. A minimum amount of dietary fat is necessary to facilitate absorption of fat-soluble vitamins (A, D, E and K) and carotenoids. Humans and other mammals have a dietary requirement for certain essential fatty acids, such as linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid) because they cannot be synthesized from simple precursors in the diet. Both of these fatty acids are 18-carbon polyunsaturated fatty acidsdiffering in the number and position of the double bonds. Most vegetable oils are rich in linoleic acid (safflower, sunflower, and corn oils). Alpha-linolenic acid is found in the green leaves of plants, and in selected seeds, nuts and legumes (particularly flax, rapeseed, walnut and soy). Fish oils are particularly rich in the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A large number of studies have shown positive health benefits associated with consumption of omega-3 fatty acids on infant development, cancer, cardiovascular diseases, and various mental illnesses, such as depression, attention-deficit hyperactivity disorder, and dementia. In contrast, it is now well-established that consumption of trans fats, such as those present in partially hydrogenated vegetable oils, are a risk factor for cardiovascular disease.A few studies have suggested that total dietary fat intake is linked to an increased risk of obesity and diabetes. However, a number of very large studies, including the Women's Health Initiative Dietary Modification Trial, an eight year study of 49,000 women, the Nurses' Health Study and the Health Professionals Follow-up Study, revealed no such links. None of these studies suggested any connection between percentage of calories from fat and risk of cancer, heart disease or weight gain. The Nutrition Source, a website maintained by the Department of Nutrition at the Harvard School of Public Health, summarizes the current evidence on the impact of dietary fat: "Detailed research—much of it done at Harvard—shows that the total amount of fat in the diet isn't really linked with weight or disease.