In

people with familial hypercholesterolemia (FH), the LDL receptors (LDLr) in

liver cells are either absent, defective, or present in reduced numbers,

leading to impaired clearance of LDL from the bloodstream. But why does this

happen? Perhaps it is worth looking at how the LDL receptor is produced in the

first place.

If

excess LDL is not cleared efficiently, it accumulates in blood vessels, leading

to the formation of atherosclerotic plaques and increasing the risk of

cardiovascular diseases. But to be cleared up efficiently, the LDL particles

need to be first taken up by the liver cells. The key to understanding how LDL

particles bind to the cell surface and are then taken up into endocytic

vesicles (endosomes) was the discovery of the 

When we eat food, dietary fats are broken down and

absorbed in the small intestine. Inside intestinal cells, they are packed into

chylomicrons (a type of lipoprotein). Chylomicrons reach the bloodstream where

they are broken down. The chylomicron remnants are taken up by the liver via

receptor-mediated endocytosis and processed. The liver then synthesizes and

releases very-low-density lipoproteins (VLDL), which are converted into LDL in

the bloodstream.

Excess LDL is taken up by the liver and other cells via

LDL receptors for breakdown or storage. If excess LDL is not cleared

efficiently, it accumulates in blood vessels, leading to the formation of

atherosclerotic plaques and increasing the risk of cardiovascular diseases.

The researcher said

that not everyone has an equal chance of getting heart attacks, and not everyone

gets atherosclerosis due to diet. This could also happen due to genetic

disorders. For instance, a person can eat fatty food and still be in perfect

health. But another person consuming the same level of fatty food could be very

susceptible to cardiac attacks. Familial Hypercholesterolemia (FH) is an

inherited genetic disorder that causes dangerously high levels of LDL or bad

cholesterol. FH is one of the most common genetic disorders that affect the

heart and blood vessels, affecting 1 in 250 people. By understanding the

underlying molecular mechanisms, we can treat this disorder.

Practice question: Which

of the following statements about FH is correct?

The

students understand the importance of this knowledge in the context of the

human health. They still had questions though: “But beyond changing our

lifestyle, how does learning these things help us actually do something about

it. Can we engineer solutions for this and apply it somehow?”

The

researcher said that is for instance what he does. He uses his fundamental

knowledge about biomolecules, cells and molecular biology to help save human

lives. And he doesn’t need to be a doctor or a medical person to do this. He is

a biological systems engineer, and he specializes on nanotheranostics to help

achieve this.

Practice

question: The research fellow believes that only doctors or medical

professional can contribute to solutions in human health?

Lipoproteins

are classified based on their size and density. Low density lipoprotein (LDL)

are often called as bad cholesterol, whereas high density lipoprotein (HDL) are

called good cholesterol.

Lipoproteins make use of the amphipathic nature of

phospholipids, which are also crucial components of the cell membrane.

Apolipoproteins are the proteins present in lipoproteins. Choose all the

correct answers from the following based on the labels (A,B, C and D) shown in

the figure:

Trans-fat is bad for health because it significantly

raises the levels of Low-Density Lipoproteins (LDL), often referred to as bad

cholesterol. This can lead to atherosclerosis and coronary heart disease.

Lipoproteins are molecules that function to transport hydrophobic molecules in

body fluids containing water. Choose all the correct options from the following:

The

students discuss that while this is interesting to know, how is this

information helpful. The researcher says that knowledge here has important

implications on health.  Plus, once you

learn the basic building blocks of life, you can see how different combinations

of the 4 main molecules (carbs, proteins, lipds, nucleic acids) leads to other

important molecules. For e.g. Carbohydrates and proteins can combine to form an

important class of molecules called glycoproteins.

Practice

question: Which of these molecules is formed predominantly by a combination of

carbohydrates and proteins?

While

this food is pretty tasty, sometimes the vendors on the streets choose to do

cost cutting and use Dalda (a form of hydrogenated vegetable oil, like

margarine, a.k.a Vanaspati Ghee). Hydrogenated vegetable oil often leads to

formation of trans fat molecules. The bottom inset in the figures shows

different molecules A, B and C which could be involved in this process.