Blood lipids
Encyclopedia
Blood lipids are lipids in the blood
, either free or bound to other molecules. They are mostly transported in a protein
capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism
. The concentration of blood lipids depends on intake and excretion
from the intestine
, and uptake and secretion
from cells. Blood lipids are mainly fatty acids and cholesterol
. Hyperlipidemia is the presence of elevated or abnormal levels of lipid
s and/or lipoprotein
s in the blood
, and is a major risk factor for cardiovascular disease
.
Blood fatty acids are in different forms in different stages in the circulation. They are taken in through the intestine in chylomicrons, but also exist in very low density lipoprotein
s (VLDL) after processing in the liver. In addition, when released from adipocytes, fatty acids exist in the blood as free fatty acids
and protein (protein coat of lipoproteins) into a compound called a chylomicron
. The chylomicron enters a lymphatic capillary and enters into the bloodstream first at the left subclavian vein
(having bypassed the liver).
In any case, the concentration of blood fatty acids increase temporarily after a meal.
from the pancreas
. As a result, the blood concentration of fatty acid stabilizes again after a meal.
s (VLDL) and again secreted into the blood.
In addition, when long time has passed since the last meal, the concentration of fatty acids in the blood decreases, which triggers adipocytes to release stored fatty acids into the blood as free fatty acids, in order to supply e.g. muscle cells with energy.
In any case, also the fatty acids secreted from cells are anew taken up by other cells in the body, until entering fatty acid metabolism
.
The 1987 report of National Cholesterol Education Program
, Adult Treatment Panels suggest the total blood cholesterol level should be: <200 mg/dl normal blood cholesterol, 200–239 mg/dl borderline-high, >240 mg/dl high cholesterol.
The average amount of blood cholesterol varies with age, typically rising gradually until one is about 60 years old. There appear to be seasonal variations in cholesterol levels in humans, more, on average, in winter. These seasonal variations seem to be inversely linked to vitamin C intake.
, which are delivered to the Portal vein and Lymph
. The chylomicrons are ultimately taken up by liver hepatocytes via interaction between apolipoproteinE and the LDL receptor
or Lipoprotein receptor-related protein
s.
; it cannot dissolve and travel in the water-based bloodstream. Instead, it is transported in the bloodstream by lipoprotein
s - protein "molecular-suitcases" that are water-soluble and carry cholesterol and triglyceride
s internally. The apolipoprotein
s forming the surface of the given lipoprotein particle determine from what cells cholesterol will be removed and to where it will be supplied.
The largest lipoproteins, which primarily transport fats from the intestinal
mucosa to the liver
, are called chylomicron
s. They carry mostly fats in the form of triglycerides. In the liver, chylomicron particles release triglycerides and some cholesterol. The liver converts unburned food metabolites into very low density lipoprotein
s (VLDL) and secretes them into plasma where they are converted to intermediate density lipoproteins(IDL), which thereafter are converted to low-density lipoprotein (LDL) particles and non-esterified fatty acids, which can affect other body cells. In healthy individuals, the relatively few LDL particles are large. In contrast, large numbers of small dense LDL (sdLDL) particles are strongly associated with the presence of atheroma
tous disease within the arteries. For this reason, LDL is referred to as "bad cholesterol".
High-density lipoprotein (HDL) particles transport cholesterol back to the liver for excretion, but vary considerably in their effectiveness for doing this. Having large numbers of large HDL particles correlates with better health outcomes, and hence it is commonly called "good cholesterol". In contrast, having small amounts of large HDL particles is independently associated with atheroma
tous disease progression within the arteries.
.
-mediated endocytosis
in clathrin
-coated pits, and then hydrolysed in lysosomes.
and intestines, start to synthesize cholesterol from acetyl-CoA
by the enzyme HMG-CoA reductase
. This is then released into the blood.
s and/or lipoprotein
s in the blood
.
Lipid and lipoprotein
abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease
. In addition, some forms may predispose to acute pancreatitis
. One of the most clinically relevant lipid substances is cholesterol
, especially on atherosclerosis
and cardiovascular disease
. The presence of high levels of cholesterol in the blood is called hypercholesterolemia
.
Hyperlipoproteinemia is elevated levels of lipoproteins.
in the blood. It is not a disease
but a metabolic
derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease
. Familial hypercholesterolemia
is a rare genetic disorder
that can occur in families, where sufferers cannot properly metabolise cholesterol.
. Research into the causes of this state is relatively limited, and while some studies suggest a link with depression
, cancer
and cerebral hemorrhage it is unclear whether the low cholesterol levels are a cause for these conditions or an epiphenomenon
http://www.americanheart.org/presenter.jhtml?identifier=1208.
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, either free or bound to other molecules. They are mostly transported in a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. The concentration of blood lipids depends on intake and excretion
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
from the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
, and uptake and secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
from cells. Blood lipids are mainly fatty acids and cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Hyperlipidemia is the presence of elevated or abnormal levels of lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s and/or lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, and is a major risk factor for cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
.
Fatty acids
Blood fatty acids are in different forms in different stages in the circulation. They are taken in through the intestine in chylomicrons, but also exist in very low density lipoprotein
Very low density lipoprotein
Very-low-density lipoprotein is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream...
s (VLDL) after processing in the liver. In addition, when released from adipocytes, fatty acids exist in the blood as free fatty acids
Intestine intake
Short- and medium chain fatty acids are absorbed directly into the blood via intestine capillaries and travel through the portal vein. Long-chain fatty acids, on the other hand, are too large to be directly released into the tiny intestine capillaries. Instead they are coated with cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and protein (protein coat of lipoproteins) into a compound called a chylomicron
Chylomicron
Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
. The chylomicron enters a lymphatic capillary and enters into the bloodstream first at the left subclavian vein
Subclavian vein
The subclavian veins are two large veins, one on either side of the body. Their diameter is approximately that of the smallest finger.-Path:Each subclavian vein is a continuation of the axillary vein and runs from the outer border of the first rib to the medial border of anterior scalene muscle...
(having bypassed the liver).
In any case, the concentration of blood fatty acids increase temporarily after a meal.
Cell uptake
After a meal, when the blood concentration of fatty acids rises, there is an increase in uptake of fatty acids in different cells of the body, mainly liver cells, adipocytes and muscle cells. This uptake is stimulated by insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
from the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. As a result, the blood concentration of fatty acid stabilizes again after a meal.
Cell secretion
After a meal, some of the fatty acids taken up by the liver is converted into very low density lipoproteinVery low density lipoprotein
Very-low-density lipoprotein is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream...
s (VLDL) and again secreted into the blood.
In addition, when long time has passed since the last meal, the concentration of fatty acids in the blood decreases, which triggers adipocytes to release stored fatty acids into the blood as free fatty acids, in order to supply e.g. muscle cells with energy.
In any case, also the fatty acids secreted from cells are anew taken up by other cells in the body, until entering fatty acid metabolism
Fatty acid metabolism
Fatty acids are an important source of energy and adenosine triphosphate 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...
.
Cholesterol
The fate of cholesterol in the blood is highly determined by its constitution of lipoproteins, where some types favour transport towards body tissues and others towards the liver for excretion into the intestines.The 1987 report of National Cholesterol Education Program
National Cholesterol Education Program
The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. Its goal is to reduce increased cardiovascular disease rates due to hypercholesterolemia in the United States of America...
, Adult Treatment Panels suggest the total blood cholesterol level should be: <200 mg/dl normal blood cholesterol, 200–239 mg/dl borderline-high, >240 mg/dl high cholesterol.
The average amount of blood cholesterol varies with age, typically rising gradually until one is about 60 years old. There appear to be seasonal variations in cholesterol levels in humans, more, on average, in winter. These seasonal variations seem to be inversely linked to vitamin C intake.
Intestine intake
In lipid digestion, cholesterol is packed into Chylomicrons in the small intestineSmall intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, which are delivered to the Portal vein and Lymph
Lymph
Lymph is considered a part of the interstitial fluid, the fluid which lies in the interstices of all body tissues. Interstitial fluid becomes lymph when it enters a lymph capillary...
. The chylomicrons are ultimately taken up by liver hepatocytes via interaction between apolipoproteinE and the LDL receptor
LDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...
or Lipoprotein receptor-related protein
Lipoprotein receptor-related protein
Lipoprotein receptor-related proteins, low density lipoprotein receptor-related proteins or prolow-density lipoprotein receptor-related protein , abbreviated LRP, are a group of proteins.They include:*LRP1*LRP1B...
s.
In lipoproteins
Cholesterol is minimally soluble in waterWater
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
; it cannot dissolve and travel in the water-based bloodstream. Instead, it is transported in the bloodstream by lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s - protein "molecular-suitcases" that are water-soluble and carry cholesterol and triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s internally. The apolipoprotein
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
s forming the surface of the given lipoprotein particle determine from what cells cholesterol will be removed and to where it will be supplied.
The largest lipoproteins, which primarily transport fats from the intestinal
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
mucosa to the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, are called chylomicron
Chylomicron
Chylomicrons are lipoprotein particles that consist of triglycerides , phospholipids , cholesterol and proteins .They transport dietary lipids from the intestines to other locations in the body...
s. They carry mostly fats in the form of triglycerides. In the liver, chylomicron particles release triglycerides and some cholesterol. The liver converts unburned food metabolites into very low density lipoprotein
Very low density lipoprotein
Very-low-density lipoprotein is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream...
s (VLDL) and secretes them into plasma where they are converted to intermediate density lipoproteins(IDL), which thereafter are converted to low-density lipoprotein (LDL) particles and non-esterified fatty acids, which can affect other body cells. In healthy individuals, the relatively few LDL particles are large. In contrast, large numbers of small dense LDL (sdLDL) particles are strongly associated with the presence of atheroma
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
tous disease within the arteries. For this reason, LDL is referred to as "bad cholesterol".
High-density lipoprotein (HDL) particles transport cholesterol back to the liver for excretion, but vary considerably in their effectiveness for doing this. Having large numbers of large HDL particles correlates with better health outcomes, and hence it is commonly called "good cholesterol". In contrast, having small amounts of large HDL particles is independently associated with atheroma
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
tous disease progression within the arteries.
Intestine excretion
After being transported to the liver by HDL, cholesterol is delivered to the intestines via bile production. However, 92-97% is reabsorbed in the intestines and recycled via enterohepatic circulationEnterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....
.
Cell uptake
Cholesterol circulates in the blood in low-density lipoproteins and these are taken into the cell by LDL receptorLDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...
-mediated endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
in clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
-coated pits, and then hydrolysed in lysosomes.
Cell secretion
In response to low blood cholesterol, different cells of the body, mainly in the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and intestines, start to synthesize cholesterol from acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
by the enzyme HMG-CoA reductase
HMG-CoA reductase
HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids...
. This is then released into the blood.
Hyperlipidemia
Hyperlipidemia is the presence of elevated or abnormal levels of lipidLipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s and/or lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
.
Lipid and lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
. In addition, some forms may predispose to acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
. One of the most clinically relevant lipid substances is cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, especially on atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
and cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
. The presence of high levels of cholesterol in the blood is called hypercholesterolemia
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
.
Hyperlipoproteinemia is elevated levels of lipoproteins.
Hypercholesterolemia
Hypercholesterolemia is the presence of high levels of cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
in the blood. It is not a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
but a metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
. Familial hypercholesterolemia
Familial hypercholesterolemia
Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein , in the blood and early cardiovascular disease...
is a rare genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that can occur in families, where sufferers cannot properly metabolise cholesterol.
Hypocholesterolemia
Abnormally low levels of cholesterol are termed hypocholesterolemiaHypocholesterolemia
Hypocholesterolemia is the presence of abnormally low levels of cholesterol in the blood . Although the presence of high cholesterol has been linked strongly with cardiovascular disease, a defect in the body's production of cholesterol can lead to adverse consequences as well...
. Research into the causes of this state is relatively limited, and while some studies suggest a link with depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
and cerebral hemorrhage it is unclear whether the low cholesterol levels are a cause for these conditions or an epiphenomenon
Epiphenomenon
An epiphenomenon is a secondary phenomenon that occurs alongside or in parallel to a primary phenomenon.-Medicine:...
http://www.americanheart.org/presenter.jhtml?identifier=1208.