ATP-BINDING CASSETTE Transport

Adenosine triphosphate (ATP) is a multifunctional nucleotide used in cells as a coenzyme. It is often called the "molecular unit of currency" of energy transfer. ATP transports chemical energy within cells for metabolism. It is produced by photo-phosphorylation and cellular respiration and used by enzymes and structural proteins in many cellular processes, including active transport, respiration, and cell division. One molecule of ATP contains three phosphate groups, and it is produced by ATP synthase from inorganic phosphate and adenosine diphosphate (ADP). ATP is used is many organisms and also in different ways. Below are a few ways in which ATP is used.

In a study conducted in 1985 observing primates, it was determined that the major effect of dietary cholesterol is its LDL raising effects. High intakes of cholesterol increase the number of circulating LDL’s and it can also change its size and composition. [12] It was during this time period that the mechanisms by which SFA are thought to increase blood cholesterol concentrations came about. One mechanism for the increase in LDL cholesterol levels is the suppression of LDL receptor activity. Studies in tissue cultures have shown that increasing the cholesterol content of a cell will down-regulate synthesis of LDL receptors. [13] This will lead to an increase in concentration of blood cholesterol. Another cause for an increase in blood cholesterol concentration through intake of dietary SFA is the composition of the newly secreted lipoproteins. With a high saturated fat intake, the LDL’s become rich in cholesterol esters, leaving the triglycerides in the blood. [14] The use of non-human primates in

Glucose is the body’s key source of energy. In order to make ATP glucose is processed from a metabolic pathway called glycolysis. The first step of glycolysis is phosphorylation of glucose. This prevents the diffusion of glucose out of the cell. Due to the charged phosphate group glucose does not easily cross the cell membrane which is where the process of facilitated diffusion comes in. Facilitated diffusion uses a channel protein to allow a component to move down it’s concentration gradient. It is also good to note that since insulin signals are synthesized at the membrane bound polyribosomes and are therefore hydrophilic, they require a TMP for transport across the lipid bilayer. These processes are possible because of ribosomes-studded

The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (EPDETHBCA) (2001), made the low density lipoprotein (LDL) their primary target of therapy, which is the major cholesterol carrying lipoprotein particle in plasma, is primarily derived from lipoprotein particles made by the liver, as the levels of LDL cholesterol increase, the risk of developing CVD increases. An estimated of 13.8% of adults have total serum cholesterol levels ≥240 mg/dL (Go et al., 2014). Saturated fatty acid and trans fatty acid intakes tend to increase LDL, which are the strongest dietary causes of elevated LDL concentrations (Lichtenstein, Ausman, Jalbert & Schaefer, 1999). The increase LDL cholesterol and reduce high density lipoprotein (HDL) cholesterol, cause endothelial damages which is the first stage in the development of atherosclerosis and may cause thrombosis afterwards (Thomas et al., 2007). Inflammation under lies atherosclerosis can be influenced positively by anti-inflammatory diet (Thomas et al., 2007). Independent of

Fluvastatin is a highly regarded drug that is involved with treating hypercholesterolemia and preventing cardiovascular disease. The drug is used to lower both high cholesterol and triglycerides levels. The drug is able to perform this task by increasing good cholesterol levels (HDL) while, at the same time, reducing bad cholesterol levels (LDL). Fluvastatin decreases the production of bad cholesterol by blocking the action of the enzyme HMG- CoA reductase in the liver. This results in a decrease in the amount of cholesterol in liver cells and subsequently leads it

Treatment with fibrate drugs acting to decrease free fatty acid production on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα is for both the conditions. The synthetic statin drugs, namely, rosuvastatin and atorvastatin can increase hepatic reuptake of LDL due to increased LDL-receptor expression, resulting in the decrease of LDL

Apo E play a role in lipid metabolism through maintaining the structural integrity of lipoproteins, serving as cofactors in enzymatic reactions, and acting as ligands for lipoprotein receptors (Eichner et al., 2002), (Chaudhary et al.,

Typically, antioxidants act as anti-inflammatories as they alleviate inflammation by neutralizing free radicals. A research demonstrated that cells recovery was induced by decreasing inflammation. Therefore, the use of suitable antioxidants is believed may be beneficial in reversing clogged arteries caused by atherosclerotic plaque build-up.

Rabbits fed HCD displayed a significant increase in serum TC, TG, LDL-C levels and atherogenic index value (LDL-C/HDL-C). Meanwhile, there was a significant decrease in serum HDL-C level compared to normal group (p < 0.001). Individual co-treatment of HCD-fed rabbits with 10-DHGD, PTX and ATOR for 12 wk significantly decreased serum levels of TC, TG and LDL-C as well as atherogenic index whereas, it increased serum HDL-C level (p < 0.001). 10-DHGD showed a more pronounced effect regarding the above mentioned parameters as compared with ATOR and PTX. Interestingly, its HDL-C raising potential was even above normal values. Finally, (10-DHGD + PTX) group demonstrated a better improvement in lipid profile and atherogenic index values with respect to individual treatments (Table

transporters vary between eukaryote and prokaryote organisms, ABC protein shows highly conservative amino acid domains within NBDs. However, NBD have three well studies motifs; ATP-binding sequences for the phosphate-binding loop (P-loop or Walker A motif), walker B boxes, and ABC signature, ex (LIVMYA), which is fix in between Walker boxes (Akifumi Sugiyama, et al, 2006)

Many research articles have characterized the oxysterol 25-OH-cholesterol (25-OH-Chol) as the most atherogenic due to its presence in macrophage foam cells extracted from atherosclerotic plaque. Other reports, however, view the oxysterol as participating in a defense mechanism against lesion development (14). This specific oxysterol can speed up degradation of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, and can sense cholesterol accumulation. As cholesterol accumulates, oxysterols can bind to alpha liver X receptors (LXRα), which regulates the expression of 7α-hydroxylase (15). This enzyme is the rate-limiting enzyme in cholesterol

ApoA-I synthesis occurs in human intestinal cells along with in the liver. Apolipoprotein (apo)A-I is a major protein component of high-density lipoproteins (HDL). Lipid poor ApoA-I interacts with ABCA-1, SR-B1 and ABCG1 to export free cholesterol (FC) and phospholipids (PL) from cells into the lipoprotein forming HDL. An important aspect of HDL is its role on the reverse cholesterol transport (RCT). In RCT, HDL exports free FC and PL from cells including macrophages in the arterial wall to the liver for excretion out of the body. This decreases sizes of plaques that form in our arterial wall which relates to an increase in cardiovascular health. Thus high levels of apoA-I in blood plasma relates to lower risk of coronary heart disease such

Lipitor a Statin drug, acts by inhibiting HMG-CoA reductase and are used as adjunct therapy to diet to reduce the risk of MI, stroke, revascularization procedures, angina , non-fatal MI, fatal and non-fatal stroke, hospitalization for CHF, reduce elevated total –C, apo B, and TG levels, increase HDL-C in adult patients with primary hyperlipidemia and mixed dyslipidemia, reduce total –C and LDL-C in patients with homozygous familial hypercholesterolemia and reduce elevated total –C and apo B levels in boys and postmenarchal girls 10-17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (Lipitor. 2012)

According to World Health Organization (WHO), Centers for Disease Control (CDC) and American Heart Association (AHA), Cardiovascular disease (CVD) is the major cause of mortality worldwide. The primary contributor to coronary artery disease and resulting cardiovascular complications pathogenesis of atherosclerosis, Atherosclerosis is chronic inflammatory process of deposition of fatty cholesterol filled plaque in arterial wall which narrows the diameter and obstructs blood flow down the length of coronary artery and throughout its branches. Nowadays, micronutrients are been studied extensively for minimizing risk intervention of CVD. Among these, dietary supplements antioxidants available over the counter are highly commercialized but scientific

Facilitated diffusion is the movement of molecules from higher to lower concentrations. Polar molecules and ions embedded in the lipid bilayer diffuse passively with the help of transport proteins that span the membrane. The layer is selectively permeable, meaning they transport some substances but not others. Within active transport there are two types of transport proteins, channel and carrier. Channel proteins provide a hydrophilic passage for a specific molecule or ion to the cross the membrane. The passageways for these proteins allow water molecules or small ions to flow very quickly from one side of the membrane to the other. Despite the small size of water molecules, movement through the phospholipid bilayer is still slower because of the polarity of the water. Another type of channel proteins is the aquaporins. Aquaporins facilitate the amounts of diffusion that occur in plant and animal cells. Another example of channel proteins are ion channels, many of which are gated channels, which open or close in response to stimuli. The stimuli can be electrical or chemical. One example of this is the nerve cell, its stimuli is the electric message sent from the brain and responds depending on the stimuli sent. Carrier proteins undergo a subtle change in the shape that somehow translocates the solute-binding site across the membrane. These changes in shape may be triggered by binding and release of the transported