LOW- DENSITY LIPOPROTEIN AND ITS DYSFUNCTIONING

About author :
Amir Khan*, Sarita Kumari 
^*Dept. of Biotechnology & Biochemistry
Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences & Research, Dehradun, India
*e-mail: [email protected]

INTRODUCTION:
Low density lipoprotein (LDL) includes a class of proteins which carry cholesterol in the blood and make it available for the use by the cells. LDL is one of the five major groups of lipoproteins (VLDL, IDL, LDL, HDL and chylomicrons) which are classified according to their size and density. An LDL particle is a microscopic blob consisting of an outer rim of lipoprotein surrounding a cholesterol center. LDL is called low-density lipoprotein because LDL particles tend to be less dense than other kinds of cholesterol particles. Each LDL particle contains a single apolipoprotien B-100 molecule, which circulates the fatty acid keeping them soluble in aqueous environment.When cell requires cholesterol,it synthesizes LDL receptors and is inserted into plasma membrane. LDL particles in bloodstream after associating with clathrin- coated pits form vesicles and binds to these extracellular LDL receptors that are endocytosed. Optimal level of LDL in humans:For good health LDL level should be low.
<100mg/dL = optimal values, 100mg/dL–129mg/dL = optimal to near optimal, 130mg/dL–159mg/dL = borderline high risk, 160mg/dL–189mg/dL = high risk,190mg/dL and higher = very high risk.
Key words: Low density lipoprotein, apolipoprotien B-100, cholesterol transport
IMPACT OF LDL ON HUMAN HEALTH:
LDL is important for cholesterol transport. The majority of cholesterol is incorporated into bile acids in the liver circulation and reused by the liver. Cholesterol is also an important component of cellular membranes and vitamin D is also synthesized from cholesterol. Approximately 25 percent of the total amount of cholesterol in the body is localized to the brain, mostly found in myelin and it ensure the rapid propagation of nerve conduction. According to one research study, LDL and triglycerides were positively associated with mood. Another study evaluated 4,115 men and 4,275 women aged 18 or older for serum lipid levels and mood. The results demonstrated a U-shaped curve, meaning that both low and high serum lipids were associated with a negative mood. In fact, the strongest association was found in men with low LDL cholesterol, showing over 5-times the likelihood of having mood changes with LDL levels below 169mg.
LDL DYSFUNCTIONING:
LDL is considered as “bad lipoprotein” due to its correlation with CVD.If LDL  is overproduced or function is impaired then it interferes with cholesterol transportation and can be associated with dyslipidemia, suboptimal cardiovascular health, low cholesterol is also associated with heart health in individuals and advanced cardiac risk. Alcohol  consumption , smoking, obesity  and many life style disorder is one of the major cause of LDL dysfunctioning.The oxidatively modified form of LDL is one of the major cause of endothelial dysfunctioning in atherogenesis. LOX-1 is receptor for oxidised LDL which under oxidative stress caused by failure of ATP generation leads to generation of reactive oxygen species and inactive NO which enhances functional changes in endothelial cells which is related to disturbed vascular homeostasis which lead to coronary heart disease. High amounts of LDL cholesterol leads to plaque growth and atherosclerosis.Some LDL cholesterol circulating through the bloodstream tends to deposit in the walls of arteries. This process starts as early as childhood or adolescence.Over time, more LDL cholesterol and cells collect in the area. The ongoing process creates a bump in the artery wall called a plaque. The plaque is made of cholesterol, cells, and debris.The process tends to continue, growing the plaque and slowly blocking the artery.An even greater danger than slow blockage is a sudden rupture of the surface of the plaque. A blood clot can form on the ruptured area, causing a heart attack. The prevalence is of dyslipidemia is highest in patients  before 55 to 60 years of age in men and before 65 years in women.Deficient LDL uptake and metabolism leads to  uncontrolled diabetes or hypothyroidism. Elevated  LDL and lack of LDL receptor enhances Amyloid –beta1-40 peptide deposition in brain leading to neurodegenerative  Alzheimer’s disease  where brain endothelial is compromise and people with Low level of LDL are more likely to have parkinson’s disease.
CONCLUSION:
Indeed, LDL is considered as ‘ bad lipoprotein’as it is associated with cardiovascular diseases and various neuro degenerative diseases like Alzheimer’s disease and Parkinson’s disease but it is bad only if its level fluctuates from the normal value otherise it is is vital for several physiological and metabolic functions of the body.