BEWARE OF SLEEPING MEDICINES

SLEEPING MEDICATION-ERRORS

BLOW HOT BLOW COLD

All experts in the medical and pharmaceutical industry, including doctors, should make warnings about sleeping pills to patients and the general public. That is not only justice and virtue but also humanity.

A 2012 survey by the Food and Drug Administration (FDA) in the United States alone found that about 500,000 people die each year from sleeping pills. Suicides were not included in this survey. It only adds to the death toll of those addicted to it that I would not get any sleep if I did not take sleeping pills daily.

According to a study, regular use of sleeping pills can cause insomnia (INSOMNIA). Thus they increase the dose spontaneously without consulting a doctor. It causes more problems. 

parasomnia is one of the bad sleeping sicknesses. It also comes down to those who abuse sleeping pills. Symptoms  

1. Awakening from sleep with confusion and instability 

2. Stunning to know where we are when we wake up. Feeling alienated from our own home. Surprise.

3. Doing things without realizing it. Such as driving. Cooking.

4. Finding abnormal wounds and marks on the body 

5. Inability to sleep at night, sleeping during the day, such as a dilemma 

Somnambulance is a sleep disorder that often affects people who take sleeping pills.

The sleep that comes with a sleeping pill is a night of bad sleep. You will feel this bad sleep as soon as you wake up. The battered model would be such an asshole. A headache will come. Constipation follows. That is what will make you feel like a patient in the course of the day you will not be active. It can also cause blurred vision, dizziness, nausea, tremors, and weakness. These are all anticholinergic effects. Click here to see more clearly about this.

Sleeping pill habits can become addictive over the course of the day and make you addicted. If you are addicted like that, then your normal sleep pattern will be disturbed as if you do not have a pill, you will not get even a normal night sleep.

The pictures below illustrate how sleeping pills can affect your nerves.

Fig-1

 

As shown in Figure 1 above, the movement of a nerve is normal. The first to be shown in Level-1 from top to bottom is the Neural System of a Nerve. It contains sodium ions outside the nerve cell and potassium ions inside. Both sides contain chloride ions. Sodium ions (Na +) are generally more positively charged (POSITIVE or + -ve) ions than potassium (K +) ions. Chloride (Cl-) ions, meanwhile, are strong NEGATIVE or -ve ions. Therefore at this polarized state, the positive energy outside the nerve cell is high (+)

Inside the cell, it is either loose (+)positively charged or strong negatively charged (-) ions.

The following hormones in the central nervous system are stimulant neurotransmitters. They are,

1) Noradrenaline, 

2) dopamine, 

3) acetylcholine, 

4) glutamate and 

5)Aspartate.

When one of these hormones binds its receptor, the charged ions begin to flow through their respective gates in and out of the nerve cell. The strongly charged sodium ions flow in, with an equal effusion of potassium ions out of the nerve cells that cause a stronger ( ➕ ) positive charge inside the cell. This condition is called cell depolarization (Figure 1-Level-2).  

In this condition the nerve cell got excited. (Figure-1, stage-3)

FIG-2

Figure-2 above is the next stage of Figure-1. That is, we saw in the illustration of Figure-1 above that under normal conditions the positive energy outside the nerve cell and the negative energy inside are in equilibrium and that this state is reversed by the stimulation of nerve stimulating hormones.

In Figure-2 we can see the attacks of nerve suppressor or suppressing hormones secreted in the same central nervous system.

The inhibitory or suppressing neurotransmitter hormones secreted in the central nervous system are as follows: -

1. GABA - GAMMA-AMINOBUTYRIC ACID

2.Glycine (GLYCINE)

3.SEROTONIN or 5-HYDROXY TRYPTOPHANE

The most important of these is GABA. During normal sleep, GABA binds to its receptor in a normal state, followed by a few chloride ions enter the nerve cells and bring the nerve to a normal polarized electrical state. (Figure-2-Level-2) This is the natural sleep state.

After taking a sleeping pill, for example, alprazolam that binds to its own receptor adjacent to the GABA receptor  (Fig-2- Level-3) causes GABA to bind its receptor firmly and very intimately (Fig-2-level-3) that follows a heavy inflow of chloride ions inside the cell and causes the nerve fibre hyperpolarized, that means it attained a state of hardness to depolarize to return to its original state. (Figure-2-Level-3). That is why the sleep that comes with a sleeping pill is not a real sleep but a sense of mild to moderate unconsciousness. Death can follow if it has been given an overdose 

Eating this often will cause your nervous system to degenerate a little bit. 

Causes neurasthenia. Over the course of the day, you will find yourself feeling like a patient. 

People who should not take sleeping pills: -

1.Drinkers who usually drink alcoholic beverages such as brandy and whiskey 

2. Addicted to drugs such as cannabis, opium, cocaine, heroin 

3.Antipsychotics such as Perphenazine, Haloperidol (Haldol), Troperidol, Closaparil (Clozaril), Risperidone (Risperdal) and the drug Chlorpromazine (Largactil) should be avoided with anxiolytics

4. People who take antidepressants such as amitriptyline

5. Cholinergic antagonists 

6. Allergy medications, including cough medicines  

How to quit sleeping pill habit?

 Those who take 10 mg daily should take it as 5 mg, those who take 5 mg daily should take it as 2 mg, and those taking it daily should take 2 mg. Eat it once a week or once a month, then cut it down to once a day or twice a day and then drop the habit immediately. 

Is Melatonin Good for Sleep?

Click here to see more about it 

What are the types of sleeping pills and their individual members under each type?

Table of Sleeping Medicines

BARBITURATES

Barbiturates like Luminal (Phenobarbital), Nembutal (Pentobarbital), Amytal (Amobarbital) and Pentothal (Thiopental) are nowadays rarely used as sleeping aids because of their serious side effects. Phenobarbital is used to control seizures as an anticonvulsant.

Thiopental is used as an anaesthetic adjuvant. For more details click here.

         

 

BEWARE OF ANTICHOLINERGICS -(MUSCARINIC RECEPTOR ANTAGONISTS)

 CHOLINERGIC NERVE BLOCKADE-EFFECTS

Before going into the subject we should basically understand what is known as the cholinergic nervous system. It is far enough to describe it very briefly as the detailed description is already available in this blog under the title, Autonomic Nervous System in parts.

Fig-1

The autonomic nervous system is pharmacologically divided into two parts as follows

1.Cholinergic N.S

2.Adrenergic N.S.

Both nervous systems are working in a balanced condition. If one system is blocked medically or mechanically then the other system predominates.

But in some areas, one system predominates and in another area, another system predominates according to the necessity and situation.

The cholinergic nervous system occupies 99% of the parasympathetic nerve supply except for the one to the sweat glands which is purely sympathetic. Further details on this subject are out of our purpose.

In the figure (Fig-1) one can easily understand the supply of cholinergic nerves to various autonomous organs.

Generally in the tranquil conditions the cholinergic N.S. predominates and on contrary in the stressful situations, the adrenergic N.S predominates. Hence the cholinergic N.S is known as the tranquil N.S and the other is known as stressful N.S. For example, in normal situations, the heart is under cholinergic control, and in stressful conditions, the control is shifted to the adrenergic N.S so that the heart rate, the pulse rate, and B.P all increase.

There are many anticholinergic drugs available on the counter of the drug stores and pharmacies that are dispensed as OTC medicines without doctors' prescriptions. The main purpose of this article is to give some detailed warnings about how the patient is affected by the misuse of these drugs.

There are many anticholinergic drugs available at the pharmacy counters as cough syrups, cold and allergy medications, sleeping medicines, psychotic and antipsychotic medications, antidiarrheals and other gastrointestinal disorders medicines, ENT preparations, ophthalmic medicines, etc. etc. These are purchased by the patients either as self medications or by the doctors prescription. Anyhow if these medicines are misused and overused they may produce harmful side effects to the body.

In the above figure (Fig-1), it is clearly mapped that the cholinergic network covers almost all over our body.

The eyes are getting clear visions by the normal cholinergic nerve influence that keeps the moisture content and secretions of the eyes properly and regulate the circular and ciliary muscle contractions to accommodate the vision and the image.

Heart with its beating rate, conduction velocity, atrial contractility and the pulses followed by the blood pressure are kept normal in peaceful situations by the balanced cholinergic influence. 

Lungs and the bronchial tree are kept moisturised with their normal secretions and are properly contracted to regulate the rate of respiration, by the balanced influence of the cholinergic nerve supply.

Stomach and intestinal muscles are properly relaxed to improve the digestive system and facilitate the defecation process.

The urinary sphincter muscle is relaxed and the bladder wall is contracted by the cholinergic balanced influence to ease the bladder emptying its urine content.

The sweat glands are supplied with both the sympathetic and the parasympathetic nervous system and in both the system the postganglionic neurotransmitter is acetylcholine. The sympathetic cholinergic secretion causes localised sweating and the parasympathetic cholinergic secretion causes generalised sweating and in both cases, the body is facilitated to eliminate the excess heat.

During coital activities, the cholinergic nerve supply to the penis helps it to get sufficient erection and help both the partners to attain orgasm.

The following secretory glands secretions under the balanced influence of the cholinergic nervous system. See the figure above (Fig-1)

1.Sweat glands -They are influenced by both sympathetic and parasympathetic nervous system in which the postganglionic neuronal transmitter is acetylcholine.

2.Intestinal secretions:- They are increased by the stimulation of the cholinergic nervous system. Thus the cholinergic nervous system speeds up the process of digestion, absorption and excretion.

3.Bronchoial secretions:- These secretions are maintained and increased by the cholinergic nervous system in order to maintain the cleanliness of the respiratory pathway and to regulate the normal respiration.

4.Lacrimal (Tear) secretions:- Cholinergic nervous system help the eyes to clean itself by its secretions and to maintain the correct intra-ophthalmic pressure (IOP).

THE CHOLINERGIC BLOCKADE-ANTICHOLINERGICS:-

Fig-2

Those drugs which block the muscarinic receptors of the postganglionic cholinergic nervous system are known as anticholinergic agents (See fig-2).

There are many medications which we commonly use with or without doctors' advises including cough syrups have anticholinergic side effects that are undesired to our purpose.

Cough syrups that contain diphenhydramine hydrochloride have anticholinergic side effects and if patients who have any one of the following conditions such as benign prostatic hyperplasia, hypertension, tachyarrhythmia (heartbeat is higher and irregular), high pulse rate, dry eyes may have moderate to serious consequences.

Constipation and Gastro Oesophagal Reflex Disease are some of the common symptoms of overusing anticholinergics such as tricyclic antidepressants (amitriptyline, imipramine, and clomipramine and Thorazine), anti-Parkinson drug under the brand Cogentin(Benztropine) trihexyphenidyl (Artane),   antihistamines (diphenhydramine hydrochloride, chlorpheniramine maleate) and anti-asthmatics (Ipratropium).

There are many anticholinergic such as atropine, scopolamine, homatropine, cyclopentolate, tropicamide and pirenzepine. Atropine is the prototype to this group and is present in Atropa belladonna plant and is a belladonna alkaloid. Atropine, homatropine and scopolamine are used to relieve stomach pain, gastrointestinal spasms and stomach ulcers. If they are overused then they may precipitate anticholinergic unbearable side effects.

Atropine, homatropine, cyclopentolate and tropicamide are also used as eye drops to produce mydriasis (dilatation of the pupil) and cycloplegia (paralysis of the ciliary muscle to relieve pain due to anterior uveitis).

Antihistaminic cough syrups such as diphenhydramine hydrochloride, chlorpheniramine maleate or simply any antihistamine contain anticholinergic effects. Antihistamine fexofenadine containing medicines may have a safe therapeutic index.

Clidinium bromide and chlordiazepoxide are the familiar drugs combination under the brand names Librocol and Librax used for stomach ulcers, stomach cramp, and IBS (irritable bowel syndrome). Both the drugs in this combination have anticholinergic effects.

Urinary incontinence (uncontrolled urination due to bladder overactivity) can be treated with the anticholinergic drug known as darifenacin (Trade names Enablex, Emselex) 

Dicyclomine + Paracetamol combination under the brand names Baralgan NU, Trigan D, and Spasidex, used for IBS, intestinal and renal colics with abdominal pain is a powerful anticholinergic combination.

Flavoxate under the brand Urispas used for urinary incontinence is an anticholinergic.

Table of anticholinergics with their brand names and uses:-

A-List of Commonly Used Anticholinergics their brand names and Uses

Anticholinergic Side Effects

1. Blurred Vision 

2.Dry Mouth

3.Urinary Retention (Difficulty in passing urine)

4.Increased and irregular heartbeat.

5.Hypertention

6.Hellucinations, delusions, tinnitus, and dementia

7.Constipation, bowel obstruction

8.Decreased sweating and hyperthermia.

In general, those who are regularly taking medicines such as antipsychotic drugs, antihistaminic drugs to treat allergy, cough, asthma and urticaria must be careful to watch the symptoms of the side effects.

Whenever any drug if you have to take chronically, please get in touch with your doctor intermittently.

A Cartoon Analogy to Explain Protein Synthesis in Eukaryotes:-

 CENTRAL DOGMA IN EUKARYOTES-CARTOON ANALOGY

A CARTOON ANALOGY

The transcription and the translation, the two major phases of the Central Dogma of a eukaryotic cell can be made easy and simplified to understand with the above shown analogous cartoon figure.

In the eukaryotes, unlike in the prokaryotes, the transcription phase occurs within the nucleus.

It is analogous to taking a copy of a particular cooking recipe from the original cookery guide book.

The original cookbook is the entire DNA chain embossed in the chromosome strand.

The particular page that contains the recipe to be transcribed is a gene portion of the DNA strand.

The copy making machine is the enzyme, DNA dependent  RNA Polymerase (RNAP).

The transcribed raw copy before the proofreading is the immature mRNA.

The proof-reader is the snRNA

After the proofreading (splicing) the matured mRNA swim out from the nucleus into the cytosol for translation.

The translation phase occurs in the cytosol.

In translation, there are many types of utensils that fit to bring suitable raw material to the cooker.

The utensils are the tRNAs

The raw materials are the amino acids

The cooker is the ribosome

The finished product is the protein molecule.

 

NINE ESSENTIAL AMINOACIDS

  ESSENTIAL AMINO ACIDS

  We have studied that protein synthesis is necessary for our body to maintain good health and energy. All our body cells are synthesizing various necessary proteins on a daily routine basis except a few which synthesize some proteins as per the body's need.

Amino acids are the basic molecules to build up proteins. There are twenty amino acids that are essential to synthesize various proteins.

Out of the 20 amino acids, our body can make only 11 amino acids. The other 9 amino acids must be supplied to our body either through food or through medicines only.

The 9 amino acids with their respective mRNA codons are the essential amino acids that the body cannot synthesize and to be supplied to the body through diet or medicines.

Generally, proteinous foods especially, meats, milk, eggs, soybeans, nuts, seeds, dry fruits are all rich in essential amino acids.

All amino acids are used to build proteins

There are additional two amino acids namely selenocysteine and pyrrolysine that do not have codons but they can be incorporated into the polypeptide chain by tRNAs holding complementary codons to the stop codon in the mRNA. Proteins containing selenocysteine are enzymes like glutathione peroxidases, tetraiodothyronine 5'-deiodinases, thioredoxin reductases, formate dehydrogenases, etc.  Proteins containing Pyrrolysine are rare can be present in archaea. 

The 9 essential amino acids are,

1.Lysine                                  

2.Leucine              

3.Isoleucine

4.Methionine

5.Phenylalanine

6.Threonine

7.Tryptophane

8.Histidine

9.Valine

Lysine containing foods 

Lysine is used especially to synthesize carnitine a group of essential substances like L-carnitine which give energy to the body. L-carnitine improves insulin sensitivity to the tissue cells.

The followings are the lysine-rich foods:-

1. Mutton, Beef, Chicken

2.Permesan Cheese (A hard full-fat Italian cheese)

3.Cod Fish and Sardines

4.Eggs

5.Soybeans, especially the curd made out of soy milk (Tofu)

6.Sprulina (A blue-green algae, a cyanobacterium belongs to Arthrospira Platensis).

7.Fenugreek Seed (வெந்தயம்)

Leucine-Rich Foods

Leucine improves protein synthesis in our body which compensates and prevents body muscle wasting.

It has been shown that leucine improves insulin production and secretions.

The followings are the Leucine-rich foods

1.Concentrated Whey Protein

2.Soy Protein concentrated

3.Pea Protein

4.Soy bean

5.Hemp seeds hulled

6.Beef

7.Salmon Fish

8.Wheat Germ

9.Almonds

10.Broiled or Fried Chicken thigh.

Isoleucine Rich Foods

Isoleucine helps our body, by regulating protein and fat metabolism, increasing protein synthesis.decreasing muscle waste.

The followings are the isoleucine rich foods:-

1.Beef

2.Veal

3.Lamb

4.Chicken

5.Wheat germ

6.Legumes

7.Seeds

8.Bakery Yeast.

Methionine

Methionine is used to prevent liver damage by paracetamol overdose. 

The followings are the methionine rich foods.

1.Ground Turkey

2.Beef

3.Tuna

4.Soya curd (Tofu)

5.Milk

6.Brazil nuts

7.Large White Beans

Phenylalanine

Phenylalanine, in addition to its effect on protein synthesis it is used to synthesize molecules that exchange signals between various body parts. Also, it is used in many skin disorders, depressions, and pain.

The followings are phenylalanine rich foods

1.Milk

2.Eggs

3.Cheese

4.Nuts

5.Chicken

6.Beans

7.Fish

Threonine

Threonine other than its role in protein synthesis it is used in nerve disorders like spinal spasticity, multiple sclerosis, familial spastic paraparesis, and amyotrophic lateral sclerosis.

The followings are the threonine rich foods:-

1.Cottage cheese

2.Chicken

3.Fish

4.Lentils

5.Lean beef

6.Soy

7.Nuts

Tryptophane

In addition to its role in protein synthesis, tryptophane also used to synthesis brain signaling molecules. The brain converts tryptophan to 5-hydroxytryptophan (serotonin) that improves our mood and sleep. Tryptophan-rich foods:-

1.Chocolate

2.Oats

3.Dried Dates

4.Milk, Yogurt, and Cottage cheese

5.Mutton, Beef

6.Eggs, and Poultry

7.Fish

8.Sesame, Chickpeas

9.Almonds and Peanuts

10.Sunlower seeds, Pumpkin seeds, buckwheat 

and Spirulina.

Histidine

In addition to its role in protein-synthesis, histidine is used in Rheumatoid Arthritis, Allergy, Ulcers, Anemia, and Kidney failure.

Histidine rich foods,

1.Poultry

2.Whole wheat grains

Valine

In addition to its role in the synthesis of protein,  valine improves muscle growth, muscle regeneration, and energy production. The followings are the valine rich foods.

1.Soy

2.Cheese

3.Peanuts

4.Mushroom

5.Beef, Chicken, Mutton.

APPLICATIONS OF GENETIC ENGINEERING-PROTEIN SYNTHESIS IN EUKARYOTES

       WONDERS OF GENE TECHNOLOGY-GENE EXPRESSION OF PROTEIN SYNTHESIS IN EUKARYOTES

Gene Technology is the altering of genetic materials by direct interventions, biomolecular behaviors, and changing genetic processes, to manufacture new medicines or to improve the functions of existing organisms.

The interesting part of genetics is how genes control the cell functions, the body's height weight, complexion the resemblance of a child to its parents, cell functions, various enzymes, antibodies, through the cell protein synthesis.

Proteins are large macromolecules made out of polypeptides that have major roles in various important functions to keep our bodies healthy. 

For example, insulin is a protein to regulate our body's glucose metabolism.

A protein is known as 'ferritin' that helps the body to store iron in the liver, marrow, and spleen.

Antibodies protecting us from infections are all various kinds of proteins.

Most of our body enzymes are made out of proteins.

Actin is the protein envelope that gives flexibility to our cells.

Our body cells contain many organelles including cell nucleus, nucleolus, endoplasmic reticulum, mitochondria that are all made of proteins.

Each and every cell of our body is a powerful factory of protein synthesis. The process involves central dogma, and gene expression to result in protein synthesis.

Synthesis of Proteins in Eukaryotic Cells:-

Fig-1

A simple eukaryotic cell has been shown above (Fig-1) that differs from the prokaryotic cell by having a defined nucleus and nucleolus. All multicellular organisms including human beings are eukaryotes. 

Transcription

The first step of protein synthesis is the transcription that is carried out in the nucleus. "The codon copying of the protein-coding genes by using DNA as a template into an mRNA which contains the message to prepare a particular protein is known as Transcription.

This is similar to copying a single recipe for a particular food from the original book of recipes.

In the nucleus, the genetic material presents as a chromosome that is a tightly twisted thread made of double-stranded DNA. Every strand of DNA is stitched with the basic units known as the nucleotides. There are four types of nucleotides used to stitch the DNA strand. They are labeled as adenine (A), guanine (G), thymine (T), and cytosine (C) nucleotides.

Fig-2

The four types of nucleotides are having the structures as shown in the figure (Fig-2)

Adenine and Guanine are known as purines

Thymine and cytosine are known as pyrimidines.

Nucleotides are formed and bonded as follows:-

Adenine and thymine nucleotides are coupled with double hydrogen bonds and guanine and cytosine nucleotides are coupled with triple hydrogen bonds in a DNA strand. All these nucleotides are stitched in as a strand fitted on a backbone contains a deoxyribose sugar ring bonded alternatively with a phosphate ion to the 5th carbon atom of one sugar ring on the upper side and to the 3rd carbon atom of another sugar ring at the lower side. See Fig-2)

There are billions of nucleotide units in each of our human body cells embedded in the chromosomes.

These nucleotides are grouped as triplets known as codons like ACC, ATC, ATG, TAG, TAC, and so on of a total of 64 codons and each represents one amino acid. Amino acids are the basic units of protein and hence to synthesize a particular protein there are a number of amino acids are required. To do this job a group of codons is to be transcribed from a particular portion of the chromosomes embedded by the DNA thread. That particular portion is known as Gene.

Fig-3

There are 23 pairs of a total of 46 chromosomes in every cell of our human body.

 Transcription:-

Fig-4

A portion of DNA is stretched from the chromosome out. An enzyme is known as DNA dependant RNA polymerase that unwinds the double-stranded DNA apart with the help of some cofactors. One of the unwinded single strands of the DNA (Template strand) is used by the RNA polymerase to transcribe the DNA codes to mRNA as shown in Fig-5 below.

Fig-5

DNA nucleotide sequence is arranged from tail to head (3' to 5') and the RNA polymerase moves and reads the codons from head to tail (5' to 3') to prepare mRNA.

Fig-5A

Thymine in DNA is replaced by Uracil in mRNA by the RNA polymerase without any change in the genetic information.

This is because thymine and uracil both are pyrimidines and have similar structures. Thymine is methyl uracil that needs more energy to move. Since DNA is unmovable and fixed within the nucleus but RNAs are mobile and must carry the genetic copy of DNA to do their job outside the nucleus they must contain lightweight uracil instead of thymine to save much energy.

Once the raw mRNA is prepared in the nucleolus they contain uncoded portions also. These portions are known as introns that are cut and trimmed out and the rest of the coded portions are joined together as an exon and exit the nucleus into the cytoplasm.

Translation:- 

Fig-6

This is the next step in the process of Central Dogma or gene expression or protein synthesis. While the step of transcription is carried out inside the nucleolus of the nucleus, the step of translation is carried out in the cytoplasm outside the nucleus.

The mRNA exited out from the nucleus reaches one of the scattered numerous numbers of mini organelles known as ribosomes embedded in the hard endoplasmic reticulum as well as free unbounded in the entire cytoplasm.

Ribosomes are tiny organelles made of 60% rRNA (ribosomal RNA) and 40% proteins. This is the protein-cooking stove. It cooks protein according to the DNA codon recipe copied in the mRNA with the help of tRNA (transfer-RNA). The tRNAs contain anticodons to read the mRNA recipe and bring the necessary amino acid ingredients to be cooked into proteins.

 The rRNA present in the ribosome cooker bonds together the amino acids into a peptide chain. 

The tRNAs start to read the mRNA from head to tail (5' to 3') direction. The first codon at the start point in the mRNA is mostly AUG that represents the amino acid methionine (Met). In the end, there is a stop codon that does not represent any amino acid with which the cooking process ends.

There are three stop codons namely, UAA, UAG, UGA is available. Anyone of them can stop the protein synthesis process.

There are 64 codons formed by the nucleotide triplets in the main DNA template. Out of that 61 codons are represented by 20 amino acids. No two amino acids are indicated by the same codon but one amino acid may have been indicated by different codons. (e.g)

Glycine is indicated by the codons GUU, GUC, GUA, GUG.

Similarly, leucine is indicated by six codons namely UUA, UUG, CUU, CUC, CUA, and CUG.

How to remember the codons and the corresponding amino acids in an easy way will be dealt with in a separate post.

Translocation: 

Protein synthesis is a cyclic process. The first tRNA that brought methionine the first amino acid come into the ribosome's A-compartment followed by moving into the P-compartment and locate the aminoacid by decoding the AUG codon in the mRNA strand by its on code UAC and after that empty tRNA moves the exit E-compartment and exit from there. By that time the ribosome moves one codon downstream to locate the next tRNA to moe in from the A site to the P site compartment to locate the amino acid which it carries and the process is going on up to the stop codon reached. During this process, one by one amino acids is spindled together as polypeptides and released out from the ribosome. The polypeptides finally polymerized together to form the final shape of a protein. These proteins are sent to the proper locations within the cell or outside the cell for utilization.

SUMMARY:-

Fig-7

In the eukaryotic cells, the protein-coding genes express their protein-synthesizing action by the above equation (Fig-7) 

DNA, the hard copy of the whole cookbook is present inside the nucleus as chromosomes. The enzyme RNA polymerase locates the gene and reads its codons for synthesizing a particular protein. It copies the codons as mRNA. This copying process is known as the Transcription. 

The mRNA swims out of the nucleus like a warm with a head and tail into the cytoplasmic colloidal fluid.

There are numerous numbers of organelles known as ribosomes scattered freely in the entire cytoplasm as well as in the endoplasmic reticulum outside the nucleus.

The ribosomes are of 80S unit which is divided into a large 60s and 40s subunits. When they unite together they will look like a hand with a clenched fist. But always they remain separated. The ribosomes contain 60% rRNA and 40% proteins. The small 40s subunit unctions to carry the mRNA on its upper platform and facilitate its codons to be readable. The large 60s subunit functions to receive the tRNA and helps it to process with bonding and fixing the aminoacids blocks brought by the tRNAs. (Fig-6). 

The mRNA enters on the upper platform of the small 40s subunit ribosome on a longitudinal direction with all its codons projecting upwards. The larger 60s subunit of the ribosome receives a tRNA with an anticodon UAC at its bottom tail end and the corresponding amino acid methionine (see Fig-6) (M) at its aminoacyl head in its A cage. After this, the tRNA moves into the P-cage where it reads the mRNA code AUG in 5' to 3' direction while the mRNA moves in the opposite 3' to 5' direction (Fig-6)

The anticodon UAC decode the codon AUG and the amino acid (M) block is removed from the tRNA head and fixed at the top of the ribosome. The emptied tRNA moves into the E cage and from there it exits out. The process continues until at least 20 to 20 amino acids are bonded by rRNA to build-up into polypeptides. As the amino acid blocks are received the rRNA translocates them in order as the first received is on the second, and the second received on the third, and so on (Fig-6).

Finally, a set of amino acid blocks are stitched to form a polypeptide and further processed into a protein molecule.

Thus synthesized proteins are either utilized intracellularly for various cell unctions or extracellularly various body functions.

The following table gives the synthetic sites and usage of some proteins:

Fig-8

A Cartoon Analogy to Explain Protein Synthesis in Eukaryotes:-

FUNDAMENTALS OF MOLECULAR BIOTECHNOLOGY-WHAT IS A GENE?

 GENE TECHNOLOGY -CONCEPTS

The main purpose of this article is everybody has a right to have a piece of minimum knowledge in molecular biology as in this pandemic COVID-19 situation, people should have at least an idea of what is going on around them to sight a solution for this adamant and strange microbiome.

Molecular biotechnology or Molecular Biology are interchangeable names to the branch of Biology, which mainly deals with the molecular behavior, changes, techniques of nucleic acid replications transcriptions and translations, and genetical modifications,etc.etc.

What are Eukaryotic and Prokaryotic Cells?

Prokaryotic cells are cells that have no defined nuclei.

e.g. Bacteria and other unicellular organisms.

Eukaryotic cells are cells that have a defined nucleus. (e.g.) human beings and other multicellular organisms.

What are the nucleic acids?

These acids are the basics of the nucleus of a cell whether the cell is prokaryotic or eukaryotic.

 RNA:-

Fig-1

Ribo Nucleic Acid. The chemical structure contains a ribose sugar attached with a purine or pyrimidine moiety at its 1st carbon position and a phosphate moiety at its 3rd carbon position. The other end of the phosphate moiety is attached with the 5th carbon position of another ribose sugar with a nitrogen base attached with its 1st carbon position. Thus a chain of ribose sugars with nitrogen bases attached by phosphate bonds is fabricated as a single RNA strand. (see Fig-1)

 DNA:-

Fig-2A

Deoxy Ribo Nucleic Acid. The chemical structure contains deoxyribose sugars attached with nitrogen bases bonded with phosphate bridges to form DNA strands. But unlike RNA, DNA is mostly available in double-stranded form.

The pentose sugar in the DNA is deoxygenated at the C'-2 position to have two hydrogen ions (one oxygen is removed) to it (H-C-H) as in the Fig-2A above. That is why it is known as deoxyribose and is more stable than ribose as the later contains oxygen at C'-2 position as (H-C-OH)

Each strand is composed of a deoxyribose ring carrying a nitrogen base (ADENINE) at the 1st carbon position attached with another deoxyribose ring with a phosphate bridge at the 5th carbon position at one end and the third carbon position at the other end. (Fig-2A)

Both RNA and DNA strands fabricated in a similar manner except one of the nitrogen bases namely thymine in DNA is replaced by uracil in RNA. Moreover, RNA is mostly occurring as a single strand whereas DNA is occurring as a double-strand spun together in a helical manner. (Fig-2B)

Fig-2B

What is a nucleotide? Nucleotides are the fundamental units of a nucleic acid strand. Every RNA and DNA strands are composed of nucleotides.

Fig-2C

Nucleotides are formed by the following equations:

A pentose back-bone+ a nitrogen base ⟶Nucleoside

A nucleoside + phosphate bonds⟶Nucleotide

A single nucleotide can be formulated as follows:

As in Fig- 2C, there are 5 nucleosides each with a pentose sugar backbone and each carrying nitrogen bases indicated by colored bands bonded together to form polynucleotides.

A pentose sugar + phosphate+ a nitrogen base.

Fig-2D

In RNA nucleotide the pentose sugar is ribose and one of the five nitrogen bases is uracil while in the DNA chain the pentose sugar is deoxyribose and one of the nitrogen bases is thymine which replaces uracil in the RNA chain. The phosphate moiety is bonding between pentoses to form the RNA or DNA backbone.

What are chromosomes?

Chromosomes are like threads made of tightly packed DNA strands packed with histones.

Fig-3

Chromosomes are formed from the twisted chain of double-stranded DNA that wrapped tightly around the pieces of proteins called histones and spun to form a rope known as chromatin which further spun tightly to form a perfect thread of chromosome (Fig-3)

In simple words, chromosomes are made of tightly wrapped DNA molecules around histones to form pairs in a eukaryotic cell nucleus.

There are about 23 pairs of chromosomes in the human cell nucleus.

A gene is any single segment of the chromosome thread which contains the heredity pieces of information including synthesizing building and demolishing or reconstructing proteins quantitatively. Genes decide the man about who he is at present and who he should be in the future. A single gene contains clear information about, physical behavior, growth, characters, and many many things.

A gene is a segment in the chromosome with a clear reading written by the jumbled nucleotide letters.

(e.g.)

Th iswh at Itr yt oexp lain-Nucleotides

This is what I try to explain-A gene

From the above anagrams, we can say nucleotides are single alphabets in a chromosome thread in an irregular scattered or jumbled manner by which a genetic character is fabricated to form a single gene.

Hence, in other words, nucleotides are scattered or jumbled chemical letters in a chromosomal thread in which a gene is fabricated by rearranging the letters to form a correct meaningful sentence that expresses a clear character. 

Thus chromosome contains many genes embossed in it.

In a human eukaryotic cell, there are 23 pairs of chromosomes of the total 46 chromosomes present.

Equation of the gene formation from the origin to end.                                                         DNA POLYMERASE

Proteins➝Nucleobases➡️Nucleotides⟶RNA⟶↲

DNA➡️DNA Helicase⟶DNA double-strand➡️histones➡️

Chromatins➡️Chromosomes➡️GENES (Fig-3)

Equation For Cell Protein Synthesis

Chromosomes➡️Chromatin➡️DNA➡️Genetic Copy(Transcription) mRNA➡️Translation by tRNA➡️Protein Synthesis by rRNA in Ribosomes.

Protein synthesis is a cyclic phenomenon. Proteins are essential for the cells to live. A cell uses proteins to make all of its contents of protoplasm, cytoplasmic organelles, nucleus, DNA, RNAs chromosomes, nucleotides, and genes. Again the gene instructs the organelle to synthesize protein. Hence it is a wonderful cyclic phenomenon in all eukaryotic and prokaryotic cells.

Next Post: Wonders of Gene Technology

HONEY AND ITS WONDERS-2-ROYAL JELLY

 ROYAL JELLY

Royal jelly is a special milky product produced by the nursing or house bees to feed the larvae. Larvae are the worm-like structures hatched from the eggs. 

The queen bee is capable of laying at least 2000 eggs per day in its lifetime. The high egg-producing ovarian capacity of the queen bee is believed to be attributed to its lifetime feeding of Royal Jelly.

The eggs after grown into larvae are identified by the nursing bees as queens, drones(kings), workers, or nurses bees and are placed in separate compartments accordingly. (See Fig-1)

After that, the nursing bees feed them with a light white jelly-like substance known as Royal Jelly.

The Royal Jelly is secreted from the glands at the hypopharynx(lower portion of the throat and the entry into the food canal) of the nursing bees.

The nursing bees feed the larvae with Royal Jelly for three days without discrimination.

But after three days they stop to feed the drone larvae, and the worker larvae but continue to feed the queen larvae with Royal Jelly until it is a well-developed queen bee with healthy ovaries. The queen bee eats Royal Jelly as its food for its entire lifetime. The other worker larvae and the drone larvae are continued to feed with honey.

Fig 2

There are three types of honey bees. They are the queen bees, the drone bees, and the worker bees. The worker bees are some times called as nurse bees or house bees.

The queen bees are the largest in size and have the longest life span. 

They are fertile females with strong well-developed ovaries that can able to lay down up to 2000 eggs per day in their lifetime. 

The queen bees have a smooth sting at its back without a barb and venom. Usually, it would not come out of the hive, and they get fewer chances of biting a human being. But often it may bite other bees. Queen bee can bite repeatedly and it would not die. (See Fig-2)

The drone bees are the next largest in size and have the shortest life span.

The drone bees are fertile male bees with the strongest sexual mating power. But during mating with the queen bee when they attain the climax the erection and ejaculation would burst its male parts and the insect dies. Hence the drones would have only one chance of having sex in its lifetime.

Drone bees have no sting at their back. (See Fig-2)

The worker bees are smaller in size than the queen and the drone bees but larger in number and have higher in the job work. They are sterile females.

The worker bee is capable of traveling long distances to collect honey.

Some worker bees stay in the hives to do domestic jobs such as preparing food and feeding the queen bee and the young larvae. 

When the worker bee brings honey the nursing or house bee receives it by mouth to mouth sucking or sucking directly from the stomach of the honey collecting bee and store it in the combs.

The worker bees are venomous and dangerous. They are very furious and curious. They are the defending soldiers of the hive. They have a strong sharply barbed sting with venom. But they will bite only once in their lifetime and they will die.

The source of Royal Jelly is the pollen grains of the flowers. While the worker bee sucks the nectar from the flower it also contaminated with pollen grains. The pollen grains are the best source of protein for honey and Royal Jelly. The worker bees are manipulating honey by adding many additives like enzymes, minerals, vitamins, phytochemicals, fatty acids, and antioxidants along with proteins from the pollen grains.

A gland at the throat side of the worker bee prepares a protein-enriched jelly with the high nutritional value from the pollen grains to feed the larvae  The food is known as the Royal Jelly. (See Fig-2)

The Compositions Of Royal Jelly:-

Water                                                     67%

Protein                                                   13%

Simple sugars(Glucose+Fructose)         12%

Fatty Acids                                             06%

10-hydroxy,2-decanoic acid (HDA)       02%

Antibiotic components                            Traces

Minerals                                                   Traces

Pantothenic Acid     (Vitamin B5)           Traces

Pyridoxin                  (Vitamin B6)          Traces

Ascorbic Acid           (Vitamin C)            Traces

But the RJ contains none of the fat-soluble vitamins such as Vitamins A, D, E, or K.

Proteins give the RJ much food value. There are five types of proteins in the RJ. They are known as Major Royal Jelly Proteins. They are MRJP-1 to 5.

The MRJP1 occupies the major position among the MRJPs. All these proteins are made by the worker bee and added to the RJ.

These proteins are attributed to be involved in differential development of the larvae into a queen and a worker bee.

Cultivation of Royal Jelly:-

Royal Jelly is produced or harvested by stimulating bees colonies with movable artificial hives to produce more queen bees. 

Several queen cells are made in the artificial hives by placing 4 days of matured queen larvae in each chamber. At least 18 days old worker bees are carefully isolated and placed in each queen chambers to secrete RJ.

The queen larvae cell contains large quantities of RJ as deposits.

A well-managed hive with more queen cells during a season of 5 to 6 months can give 600gms of RJ.

Is RJ is beneficial to human beings?

There are many controversial and confused beliefs regarding this. There are very little medical proofs available about the benefits of RJ in people.

The compositions of RJ include proteins, fats, sugars vitamins, minerals, and many things that are good for health but most of them are present in traces which is sufficient only for a small insect, like the honey bee.

There is a belief that the transfat present in the RJ yields health benefits to the heart. Doctors recommend RJ as cardioprotective.

The protein and fat of the RJ are believed to be improving male sexual vigor and potency. 

Some researchers say that there are possible beneficial relieving effects from menopausal sufferings.

RJ may improve feelings of well being in menopausal women.

Insufficient pieces of evidence of benefits for the following discomforts:-

1.Diabetic foot ulcers

Some early researches showed that applying a mixture of RJ and panthenol in a cream or ointment base for six months after cleaning and removing dead tissues may give beneficial relief.

2.Infertility.

It was believed in early days that applying a mixture of RJ, honey, and bee bread to the vagina for two weeks may increase the rate of pregnancy in couples with fertility problems due to reduced sperm movement (asthenozoospermia)

3.High Cholesterol

It is suggested by early research that taking RJ by mouth, by injection or by sublingual may reduce blood cholesterol.

4.Premenstrual Syndrom (PMS).

It is suggested by early research that taking products containing RJ, bee pollen, pollen and pistil extract by mouth for two menstrual cycles seems to relieve symptoms of PMS such as irritability, weight gain, and swelling.

5.Asthma 

6.Liver Diseases

7.Pancreatitis

8.Sleeping trouble

9.Stomach ulcers

10.Kidney Disease

11.Bone Fractures

12.Skin Disorders

13.Baldness

14.Immunity-Boosting

Shreds of evidence are not sufficient to rank the efficacy of RJ for the above uses.

Safety Concerns.

Royal Jelly and its combinations may cause allergic reactions such as respiratory distress in asthma patients.

Usually, RJ is skin-friendly but when applied to the scalp it often produces allergic reactions such as inflammations and rashes.

It often causes swelling of the throat and death if a person is allergic to it.

Royal Jelly lowers blood pressure. Patients with low B.P. and those who take B.P. medicines for hypertension should not take RJ.

People with skin irritation and swelling should better avoid the use of RJ.

RJ may produce stomach pain and diarrhea.

Contraindications

1.Warfarin-An anticoagulant similar to clopidogrel

2.B.P.medicines-like atenolol,metoprolol,enalapril,amlodipine,nifedipine,

3.Co-enzyme Q-10-Food supplement

4.Fish oil           - Food supplement

5.Casein protein-Food supplement

L-Arginine         -Aminoacid,-Food supplement

Lycium               -Food supplement

Stinging nettle    -Food supplement

Theanine             -Amino acid

Proved Benefits of Royal Jelly:

1. If you are otherwise a healthy person not using any B.P control medicines RJ is perfect for you to maintain your blood pressure

2. Royal Jelly is good for heart functions through its hypotensive effect.

3. Royal Jelly antioxidants and hence reduce the risks of cancers.

4. Royal Jelly has anti-inflammatory effects.

5. Royal Jelly is a protein food supplement which is good for blood pressure.

6. Regulate blood sugar levels.

7. Royal Jelly is believed to have anti-bacterial effects.

8. Royal Jelly may provide relief from menopausal symptoms. (150mg/day for 3 months may improve cholesterol levels in menopausal women)

9. Some study results have shown that RJ is reducing blood glucose levels.