Dietary triacylglycerols and cholesterol, as well as triacylglycerols and cholesterol synthesized by the liver, are solubilized in lipid-protein complexes called lipoproteins. The protein particles have hydrophilic groups aimed outward so as to attract water molecules; this makes them soluble in the salt water based blood pool. Triglyceride-fats and cholesterol are carried internally, shielded from the water by the protein particle. The interaction of the proteins forming the surface of the particles with (a) enzymes in the blood, (b) with each other and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.
General categories of lipoproteins, listed in order from larger and less dense (more fat than protein) to smaller and denser (more protein, less fat):
Chylomicrons - carry triacylglycerol (fat) from the intestines to the liver, skeletal muscle, and to adipose tissue.
Very low density lipoproteins (VLDL) - carry (newly synthesised) triacylglycerol from the liver to adipose tissue.
Intermediate density lipoproteins (IDL) - are intermediate between VLDL and LDL. They are not usually detectable in the blood.
Low density lipoproteins (LDL) - carry cholesterol from the liver to cells of the body. Sometimes referred to as the "bad cholesterol" lipoprotein.
High density lipoproteins (HDL) - collects cholesterol from the body's tissues, and brings it back to the liver. Sometimes referred to as the "good cholesterol" lipoprotein.
Inner core: triaglycerides and cholesterol esters
Outer core: phospholipids, apoproteins, unesterified cholesterol, enzymes e.g. LCAT
Effects of disorders in lipoprotein metabolism
Blood vessel sclerosis
Xanthomas -are skin lesions caused by the accumulation of fat in macrophage immune cells in the skin and more rarely in the layer of fat under the skin.
Metabolism of LDL fraction
LDL binds to LDL receptors on cell membrane
The LDL complex is intcmalised by endocytosis.
Vesicle containing LDL looses its coat and fuses with other similar vesicle- endosome.
The pH of the endosome falls due to proton pumping, allowing separation of LDL from its receptor.
LDL is free in the vesicle lumen
Lipoprotein remnants in the vesicle are transferred to liposomes and degraded by lysosomal and hydrolases, releasing these substances which are used by the cell:
Ammonia is produced from dietary amino acids and by catabolism of amino acids, amines, nucleic acids, glutamine and glutamate (nitrogenous wastes) in peripheral tissues (especially skeletal muscle).
Gastrointestinal microorganisms (primarily coliforms and anaerobes in the colon and cecum) convert dietary amino acids and urea into ammonia in the gastrointestinal system. The ammonia attaches to glutamate forming glutamine, a process catalyzed by glutamine synthase and is then transported to the liver. The ammonia is absorbed into the portal circulation, taken up by the liver and converted in the liver, via the urea cycle, into urea. Urea is then excreted into the gastrointestinal system (producing a futile cycle) and into the urine. Of the total ammonia produced, 80-90% is shunted into the urea cycle, with the remaining 10-20% metabolized by peripheral tissues, including the kidney, heart, and brain.
Alanine serves as a carrier of ammonia and of the carbon skeleton of pyruvate from skeletal muscle to the liver.
Phenylketonuria: occurs in infants that can't break down phenylalanine. Phenylalanine is toxic to the brain and builds up in blood. Phenylketonuria is caused by lack of the enzyme needed to convert phenylalanine to tyrosine. Symptoms: intellectual disorder, seizures, nausea and vomiting.
Homocystinuria: lack of enzyme needed to metabolize the amino acid homocystein. First symptoms: dislocation of the eye lens, skeletal abnormalities, children are tall, thin with curved spine and elongated limbs. When given B6, B12 improvement.
Maple syrup urine disease: Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. Beginning in early infancy, this condition is characterized by poor feeding, vomiting, lack of energy (lethargy), and developmental delay. If untreated, maple syrup urine disease can lead to seizures, coma, and death.
Albinism: is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of tyrosinase, a copper-containing enzyme involved in the production of melanin. Albinism results from inheritance of recessive gene alleles and is known to affect all vertebrates, including humans. While an organism with complete absence of melanin is called an albino an organism with only a diminished amount of melanin is described as albinoid. Albinism is associated with a number of vision defects. Lack of skin pigmentation makes for more susceptibility to sunburn and skin cancers.