Question

1. Discuss the structural organization of lipoprotein particles such as HDL, LDL or VLDL. List all of the biomolecules found in each and describe their function in the particle. How does their structure facilitate the function of the particles? What does each do? (9 points).

2. Find three diseases in humans where there is a metabolic defect that results in an inability to process or metabolize specific
3. Lipids
4. Proteins or amino acids
5. Fats (lipids)

For each disease, explain the pathophysiology of the disease and the symptoms that an individual with the disease experiences. (9 points)

3. In the scientific literature, find a clinical trial that is prospective randomized as well as placebo-controlled. List the reference for the paper and explain the method of how the scientists randomized the trial and what the treatment groups were. Did the trial you found have any other features such as being a crossover trial or being blinded. (Extra credit is possible if you find these additional features). (10 points)

4. Technetium 99m and fluorodeoxyglucose are two radioisotopes frequently utilized in clinical medicine. Find two specific applications (tests or treatments) for each and describe how they are utilized. (8 points)

5. Describe how DNA is organized such that 46 chromosomes with approximately 3 billion bases are able to fit in the limited space of the nucleus of a cell. In addition, how does transcriptionally active DNA differ from DNA that is not being transcribed? (6 points)

Answer 1

Structural organization of lipoprotein:

HDL : HDL particles are plurimolecular, quasi-spherical or discoid, pseudomicellar complexes composed predominantly of polar lipids solubilised by apolipoproteins. HDL also contains numerous other proteins, including enzymes and acute-phase proteins, and may contain small amounts of nonpolar lipids.

LDL : Overall the LDL particle is organized into two major domains: namely a central apolar core of cholesteryl esters and minor amounts of triglycerides surrounded by an amphipathic shell consisting of a phospholipid monolayer, free unesterified cholesterol and a single molecule of apolipoprotein B-100 (apoB-100).

VLDL: Very low density lipoproteins (VLDL): These particles are produced by the liver and are triglyceride rich. They contain apolipoprotein B-100, C-I, C-II, C-III, and E. Apo B-100 is the core structural protein and each VLDL particle contains one Apo B-100 molecule.

There are four major classes of Biomolecules – Carbohydrates, Proteins, Nucleic acids and Lipids.

Carbohydrates

Carbohydrates are chemically defined as polyhydroxy aldehydes or ketones or compounds which produce them on hydrolysis. In layman’s terms, we acknowledge carbohydrates as sugars or substances that taste sweet. They are collectively called as saccharides (Greek: sakcharon = sugar). Depending on the number of constituting sugar units obtained upon hydrolysis, they are classified as monosaccharides (1 unit), oligosaccharides (2-10 units) and polysaccharides (more than 10 units). They have multiple functions viz. they’re the most abundant dietary source of energy; they are structurally very important for many living organisms as they form a major structural component, e.g. cellulose is an important structural fibre for plants.

Proteins

Proteins are another class of indispensable biomolecules which make up around 50% of the cellular dry weight. Proteins are polymers of amino acids arranged in the form of polypeptide chains. The structure of proteins is classified as primary, secondary, tertiary and quaternary in some cases. These structures are based on the level of complexity of the folding of a polypeptide chain. Proteins play both structural and dynamic roles. Myosin is the protein that allows movement by contraction of muscles. Most enzymes are proteinaceous in nature.

Nucleic Acids

Nucleic acids refer to the genetic material found in the cell that carries all the hereditary information from parents to progeny. There are two types of nucleic acids namely, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The main function of nucleic acid is the transfer of genetic information and synthesis of proteins by processes known as translation and transcription. The monomeric unit of nucleic acids is known as nucleotide and is composed of a nitrogenous base, pentose sugar, and phosphate. The nucleotides are linked by a 3’ and 5’ phosphodiester bond. The nitrogen base attached to the pentose sugar makes the nucleotide distinct. There are 4 major nitrogenous bases found in DNA: adenine, guanine, cytosine, and thymine. In RNA, thymine is replaced by uracil. The DNA structure is described as a double-helix or double-helical structure which is formed by hydrogen bonding between the bases of two antiparallel polynucleotide chains. Overall, the DNA structure looks similar to a twisted ladder.

Lipids

Lipids are organic substances that are insoluble in water, soluble in organic solvents, are related to fatty acids and are utilized by the living cell. They include fats, waxes, sterols, fat-soluble vitamins, mono-, di- or triglycerides, phospholipids, etc. Unlike carbohydrates, proteins, and nucleic acids, lipids are not polymeric molecules. Lipids play a great role in the cellular structure and are the chief source of energy.

Cholesterol and triglycerides are fatty molecules. Because of their fat-like properties, they are not able to easily circulate in the bloodstream. In order for cholesterol and triglycerides to travel in the blood, they are often carried by proteins that make the cholesterol and triglycerides more soluble in blood. This lipid and protein complex is referred to as a lipoprotein.

Functions:

VLDL :

VLDL is made in the liver and is responsible for delivering triglycerides to cells in the body, which is needed for cellular processes. As triglycerides get delivered to cells, VLDL is made up less of fat and more of protein, leaving cholesterol on the molecule.

LDL : Elevated LDL levels are associated with an increased risk of cardiovascular disease. Certain forms of LDL—specifically small, dense LDL (sdLDL) and oxidized LDL (oxLDL)—have been associated with promoting the formation of atherosclerosis by depositing fats on the walls of arteries in the body. Because increased levels of LDL are associated with the development of cardiovascular disease, LDL is also known as the “bad” cholesterol.

HDL : HDL is made in the liver and in the intestines. It is responsible for carrying cholesterol from cells back to the liver. Because of this, HDL is also considered the “good” cholesterol.

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