My Graduate Studies Journey: #RoadToMSChemistry (An Update)

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Series of problem sets and take home examinations

It has been two years since I mentioned my graduate study journey at Central Luzon State University. 

Back in 2021, the online classes began, and they posed a unique set of challenges. All of my classes were scheduled for Saturdays, which happened to coincide with my weekly work meetings.

Work meetings and online class at the same time

Most of the time, I found myself juggling two gadgets simultaneously to attend both online activities. This constant balancing act defined my academic year.

Moving on to the following academic year, things took a more challenging turn. I had a laboratory class that required face-to-face sessions.

To accommodate this, our weekly work meetings were rescheduled to Tuesdays, and I was immensely grateful for the adjustment, as it allowed me to accumulate leave credits by not attending classes on Saturdays.

One of our laboratory class

Fortunately, our professor displayed great understanding and allowed me to skip Saturday classes, provided I made up for them by keeping up with the course activities.

Working on isolation of egg protein

Measuring the total protein from egg

The laboratory class was particularly significant, as it covered various aspects of my thesis work, using a plant of special interest to me—Clerodendrum schmidtii, also known as the Nodding Clerodendrum or commonly referred to as Indian Beads.

My plant of interest: Clerodendrum schmidtii or Idian Beads

Working on my thesis

As I moved into my last semester, I faced the challenge of both laboratory and lecture classes, both held in a face-to-face format. My days began at 6:30 am and didn't conclude until 5:00 pm, all for just two subjects.

Even after the last semester ended, I still had a special topic subject assigned for the mid-term. We were tasked with selecting a special topic from a journal and required to conduct a comprehensive journal review, which we then had to present in class.

My special topic in Biochemistry

Aside from the special topic presentation, majority of our subjects require a journal review and presented as a seminar to our classmates and even BSChemistry Students.

Behind the scenes in some of the seminar presentations

After enduring four semesters and one mid-term, I am pleased to share that I successfully passed all of my subjects. 

Acamedic subjects: Passed, Thesis: In-progress

Currently, I am eagerly awaiting the schedule for the comprehensive exam and hope to emerge victorious. I've also taken the initiative to forward my thesis draft to my advisor, eagerly anticipating her feedback, with hopes of presenting my proposal before the semester draws to a close.

With determination and perseverance, I am steadfast in my goal to retrace the same educational pathway I embarked on twenty years ago and ultimately earn my well-deserved diploma.

I'll make a follow-up post on my journey to #RoadToMSChemistry.

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Curing African Sickness Using Biological Trojan Horse

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On my previous post, I mentioned that I will be shariing some of the topics on my #RoadToMSChemistry Journey. Here is one of the topics and this is how it was written including the references.

Curing African Sickness Using Biological Trojan Horse

When we hear or read the word Trojan Horse, we usually referred to the wooden horse used by the Greeks during the Trojan War. However, in the modern era, it is known as a computer malware that mimics a legitimate program ending up with phishing and spying of a computer’s content. (“What Is a Trojan Horse? Trojan Virus and Malware Explained”).

‌Since Trojan Horse is related to a virus, how about living things- humans and animals? Can there be also the so-called biological Trojan Horse?

Studying enzymes, particularly in irreversible inhibitors, lead to the discovery of new drugs and is considered to be one of the Biological Trojan Horses. These inhibitors react by attaching themselves to the functional groups of enzymes which are responsible for the primary enzyme’s activity. Once the covalent bond was formed between the active sites of the enzyme and irreversible inhibitor, the former will be deactivated halting the cell’s growth and reproduction (Nelson 571–572).

One type of irreversible inhibitor is the suicide inactivator or also called mechanism-based inactivators. These inactivators react only upon binding with the enzyme’s active site. Upon reacting with the active site, instead of producing a common product from an enzymatic reaction, it will create a highly reactive substance that will combine and inactivates the enzyme.

How do these Biological Trojan Horses use in the field of medicine? One example of the study of enzymes and suicide inactivators is in the treatment of African Sleeping Sickness.

African Sleeping Sickness, is commonly observed in the East and West parts of the African Continent. It is caused by a unicellular protozoan trypanosome (T. brucei rhodesience and T. brucei gambiense,) carried by the tsetse fly (Pascholati et al.). At first, this illness is manageable not until the late 20th century. With the continuous changes in the virus’ protection coat or antigen, vaccines are no longer effective as they should be (Nelson 571–72).

One mechanism studied in the treatment of African Sleeping Sickness is the reaction catalyzed by ornithine decarboxylase with diflouromethylornithine (DMFO) as suicide inactivators (Reddy, ch.2).

How does the reaction go?

Figure 1. ODC-catalyzed biosynthesis pathway forming putrescine and regeneration of PLP.

The primary step in decarboxylation of ornithine, with pyridoxal phosphate (PLP) as a co-factor, is the formation of Schiff base, an imine intermediate. This will go a rapid reaction forming putrescine, diamime and regenerates PLP (Figure 1) (Reddy, ch.2)

Putrescine is the diamine needed in the biosynthesis as precursor of polyamines spermine and spermidine which is an essential part of eukaryotic cells (Poulin et al.). 

The presence of a suicide inactivator diflouromethylornithine (DMFO) in the reaction with PLP forms a Schiff base which proceeds with the elimination of fluorine atom and carbon dioxide forming a secondary metabolite flouroolefin derivative. This terminal flouroolefin part will become highly reactive with the nuclephilic thiol residue at the enzyme’s active site. This will undergo Michael’s addition followed by a fast elimination of the fluorine atom forming an inactivated enzyme (Figure 2)(Reddy, ch.2).

Figure 2. Reaction pathway of DFMO and PLP forming a highly reactive Schiff base. Upon further reaction with the enzyme active site, it will for an inactivated ezyme.

With the continuous study and research in enzymology and metabolism, more and more drugs or treatments will be discovered especially to the diseases that are currently incurable. Although it will take several times, Biological Trojan Horses are just around the corner waiting to be found.

References:

Nelson, David. Lehninger Principles of Biochemistry. 7th ed., W.H. Freeman, 2017.

Pascholati, Cauê P., et al. “The Interaction of an Antiparasitic Peptide Active against African Sleeping Sickness with Cell Membrane Models.” Colloids and Surfaces B: Biointerfaces, vol. 74, no. 2, 2009, pp. 504–10. Crossref, https://doi.org/10.1016/j.colsurfb.2009.08.018.

Poulin, R., et al. “Mechanism of the Irreversible Inactivation of Mouse Ornithine Decarboxylase by Alpha-Difluoromethylornithine. Characterization of Sequences at the Inhibitor and Coenzyme Binding Sites.” Journal of Biological Chemistry, vol. 267, no. 1, 1992, pp. 150–58. Crossref, https://doi.org/10.1016/s0021-9258(18)48472-4.

Reddy, Prakash. Organofluorine Compounds in Biology and Medicine. Elsevier Gezondheidszorg, 2015.

“What Is a Trojan Horse? Trojan Virus and Malware Explained.” Fortinet, www.fortinet.com/resources/cyberglossary/trojan-horse-virus. Accessed 17 Mar. 2022.

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An Understanding of Protease Mechanisms Lead to New Treatments of HIV Infection

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In time with the HIV Awareness Month, I am glad to share one of my reaction papers in my graduate study program.

I hope that this can somewaht add information about human immunodeficiency virus or HIV.

 An Understanding of Protease Mechanisms Lead to New Treatments of HIV Infection

“…I would raise awareness to certain causes like HIV awareness that is timely and relevant to my country, which is the Philippines…” This is one part of Pia Wurztbach’s response to the final Q&A of Miss Universe 2015 where she hooked the crown.

What is the real status of HIV in the Philippines?

The case of HIV in the Philippines increased up to 207% from 2010 to 2019 with a death toll increase of 338%. This is considered the fastest rising in the Asia and Pacific region. In 2019, there are about 97,000 persons living with HIV or PLHIV. The majority of these PLHIV are persons who injected drugs, men who have sex with men, sex workers, and transgender (Nguyen).

The virus can be transmitted through body fluids like blood, breastmilk, semen, and vaginal secretions but does not pass by kissing, hugging, sharing food, or drinks (“HIV/AIDS”).

Human immunodeficiency virus or HIV is the main causative agent of acquired immune deficiency syndrome or AIDS, which emerges in the 80s and is considered an epidemic worldwide.

HIV is a retrovirus having its genetic information is in the form of RNA and has a reverse transcriptase enabling the virus to use the RNA in the synthesis of complementary DNA (Nelson, 587).

How do HIV infection proceeds?

The infection occurs when the viral and cellular membrane fused with the facilitation of viral envelope glycoprotein and the receptors CD4 of the target cells.

When the virus enters the cell, its RNA is reversed-transcribed to DNA by the reverse transcriptase. The HIV genetic material will combine with the host’s cell using the integrase enzyme followed by transcription into the messenger RNA and replicated into viral polyproteins. The HIV protease will incise these polyproteins to form new virions and become ready to infect another host’s cell. With the destruction of the host’s genetic materials and continuous production of virions results in the death of infected cells (Brik and Wong 5–14).

Figure 1. The life cycle of HIV (“Life Cycle | NIH”)

 

Based on the mechanism, there are 3 major enzymes of the HIV used in the cycle – reverse transcriptase, integrase, and HIV protease. With these three enzymes, the HIV protease is the most studied in the development of treatments against HIV.

Proteases are classified into two huge groups according to their ability to catalyze the mechanism. The first class uses a nucleophilic atom, either hydroxyl or thiol of the amino acid side chain to start the amide hydrolysis (Brik and Wong 5–14).

The second classification requires two aspartyl β-carboxyl groups in the enzymatic sites to activate a water molecule for nucleophilic reaction on a peptide bond. It is referred to as aspartyl protease where HIV protease belongs (Windsor et al. 1465).

One way to inhibit the proliferation of HIV is by disturbance of the HIV protease enzyme responsible for the breakdown of polyprotein virus using protease inhibitors called anti-retroviral or ARVs. Here are several USFDA-approved ARVs given to PLHIV (Brik and Wong 5–14).

Figure 2. Structures of different HIV protease inhibitors or antiretrovirals.

The different HIV protease inhibitors vary in their structures but have similarities in terms of the main chain with a hydroxyl group in the β-position from the benzyl group (Nelson, 589).

Refer to the figure below regarding one of the accepted mechanisms for the aspartyl protease (HIV protease) mechanism.

 

Figure 3. One of the acceptable mechanisms of HIV protease.

Studying the mechanisms for HIV protease enzyme, and other enzymes is a good starting point in the discovery of new drugs that can cure (or at least control its progress) not only HIV but also other chronic illnesses. The available ARVs help extend the lifespan of the PLHIV.

Recently, there is a reported case of PLHIV cured of the said retrovirus. The patient undergoes stem cell treatment using cord blood with the mutation that prevents the entrance of HIV into the cell. Thirty-seven (37) months after the transplant, the patient chooses to top the use of ARVs. After 14 months, the patient did not show any signs of HIV in the blood tests as well as detectable antibodies to the virus (Mandavilli).

With this information, it can be a great breakthrough for researchers to further study the mechanism on how the stem cell procedure works in killing the HIV in the body which will lead to the right medicine or drug in the cure of this incurable disease.

References:

Brik, Ashraf, and Chi-Huey Wong. “HIV-1 Protease: Mechanism and Drug Discovery.” Organic & Biomolecular Chemistry, vol. 1, no. 1, 2002, pp. 5–14. Crossref, https://doi.org/10.1039/b208248a.

 

“HIV/AIDS.” WHO, 30 Nov. 2021, www.who.int/news-room/fact-sheets/detail/hiv-aids.

 

“Life Cycle | NIH.” CLINICAL INFO.HIV.GOV, clinicalinfo.hiv.gov/en/glossary/life-cycle. Accessed 21 Mar. 2022.

 

Mandavilli, Apoorva. “A Woman Is Cured of H.I.V. Using a Novel Treatment.” The New York Times, 22 Feb. 2022, www.nytimes.com/2022/02/15/health/hiv-cure-cord-blood.html.

 

Nelson, David. Lehninger Principles of Biochemistry. 7th ed., W.H. Freeman, 2017.

 

Nguyen, Alice. “The HIV Epidemic in the Philippines: Affected Populations.” The Borgen Project, 26 Jan. 2021, borgenproject.org/hiv-epidemic-in-the-philippines.

 

Windsor, Ian W., et al. “An N→π* Interaction in the Bound Substrate of Aspartic Proteases Replicates the Oxyanion Hole.” ACS Catalysis, vol. 9, no. 2, 2018, pp. 1464–71. Crossref, https://doi.org/10.1021/acscatal.8b04142.

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Defective Glucose and Water Transport in Two Forms of Diabetes (Part 3 of 3)

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Diabetes is about sugar and the one that helps in regulating this compound in our body is the insulin secreted by the pancreas. 

Did you know that insulin is accidentally discovered? Have you ever heard that the first commercially available insulin in the market is extracted from a pig's pancrease?

Here is the last part of one on the topics in Biochemistry about diabetes - about insulin.

Defective Glucose and Water Transport in Two Forms of Diabetes (Part 3 of 3)

Insulin: Discovery, Purification, and Mechanism

Insulin is accidentally discovered in 1889 by Oscar Minkowski and Josef von Mering after a friendly disagreement about whether the pancreas contains lipase. They surgically remove the pancreas of a dog for the study which eventually observed to urinate more. However, they failed to extract substance to reverse the effect of removing the pancreas (Nelson).

Not until 1921 when Frederick Banting, Charles Best, and JJR MacLeod took up the problem and found anti-diabetic factors in the pancreas. They called it insulin from the Latin word “insula”, meaning islands since insulin was extracted from the islets of Langerhans. The same year, purification was successful (“Insulin | Definition, Structure, and Function”).

In 1922, they tested the purified insulin on Leonard Thompson and within a few days, they observed a drop of glucose and ketone in the body (Nelson).

A Nobel Prize was awarded to Banting and MacLeod in 1923 and since then insulin was isolated from the porcine pancreas. In 1980, through genetic engineering techniques, the mass production of insulin was developed (“Insulin | Definition, Structure, and Function”).

Insulin is composed of two chains of amino acids derived from preproinsulin. Preproinsulin is an inactive substance of Chain A, Chain B, C-peptide, and a signal peptide. When the preproinsulin reached the Endoplasmic reticulum, the signal peptide will be cleaved off leaving the still inactive proinsulin. As it procced to the Golgi apparatus, a disulfide bond in the cysteine residue is formed and the C-peptide will eventually cleave off producing the active insulin while the C-peptide will be degraded and excreted. (Vasiljević, et al.).

Figure 4. Synthesis of insulin from preproinsulin.

Diabetes is often related to blood sugar with the early signs or symptoms of excessive urination. However, there are two forms of diabetes – diabetes mellitus and diabetes insipidus. The urine in diabetes mellitus is sweet while in diabetes insipidus is very dilute or tasteless.

Both forms of diabetes are hormone-related. Insulin is secreted by the pancreas for diabetes mellitus while vasopressin is secreted by the pituitary glands for diabetes insipidus.

Diabetes prevalence in the Philippines is quite alarming. This only gives us the warning to keep our health monitored and choose a lifestyle that will keep us fit.

 

References:

Baclig, Cristina Eloisa. “Diabetes: A Bitter Health Crisis for Filipinos.” INQUIRER.Net, 21 July 2021, newsinfo.inquirer.net/1461980/diabetes-a-bitter-health-crisis-for-filipinos.

Bryant, Nia J., et al. “Regulated Transport of the Glucose Transporter GLUT4.” Nature Reviews Molecular Cell Biology, vol. 3, no. 4, 2002, pp. 267–77. Crossref, https://doi.org/10.1038/nrm782.

 

“Diabetes Insipidus and Diabetes Mellitus.” The Diabetic Voice.Com, www.the-diabetic-voice.com/diabetes-insipidus-and-diabetes-mellitus.html. Accessed 26 Apr. 2022.

 

Felman, Adam. “What’s to Know about Diabetes Insipidus?” Medical News Today, 7 Apr. 2022, www.medicalnewstoday.com/articles/183251.

 

“Glucose Regulation and Utilization in the Body.” Nutrition FN 225, media.lanecc.edu/users/powellt/FN225OER/Carbohydrates/FN225Carbohydrates5.html. Accessed 26 Apr. 2022.

 

“Insulin | Definition, Structure, and Function.” Encyclopedia Britannica, www.britanica.com/science/insulin.

 

Nelson, David. Lehninger Principles of Biochemistry. 7th ed., W.H. Freeman, 2017.

 

Qureshi, Sana, et al. “Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy.” Endocrinology, vol. 155, no. 12, 2014, pp. 4605–21. Crossref, https://doi.org/10.1210/en.2014-1385.

 

Tahrani, Abd A., et al. “Management of Type 2 Diabetes: New and Future Developments in Treatment.” The Lancet, vol. 378, no. 9786, 2011, pp. 182–97. Crossref, https://doi.org/10.1016/s0140-6736(11)60207-9.

 

Vasiljević, Jovana, et al. “The Making of Insulin in Health and Disease.” Diabetologia, vol. 63, no. 10, 2020, pp. 1981–89. Crossref, https://doi.org/10.1007/s00125-020-05192-7.

 

“What Is Diabetes?” Centers for Disease Control and Prevention, 2 Mar. 2022, www.cdc.gov/diabetes/basics/d

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Defective Glucose and Water Transport in Two Forms of Diabetes (Part 2 of 3)

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Did you know that there is another type of diabetes? It is not related to sugar but with the function of water retention by the kidney.

Here is the second part of my report concerning about diabetes.

Defective Glucose and Water Transport in Two Forms of Diabetes (Part 2 of 3)

Diabetes Insipidus

Diabetes insipidus is similar to diabetes mellitus. Instead of glucose, it is all about the re-absorption of water from the urine to the bloodstream. The hormone responsible for this condition is the vasopressin produced in the pituitary gland (Felman).

Instead of the GLUT4, aquaporin is present in the collecting duct in the kidney. These are responsible for the absorption and re-absorption of water.

The aquaporins 3 and 4 (AQP3 and AQP4, respectively) are located in the basolateral membrane of the urine-collecting duct in the kidney. Aside from AQP3 and AQP4, there is aquaporin AQP2 that will attach itself to the apical membrane where the diluted urine flows. This only happens when the arginine-vasopressin (AVP) binds with its receptor. The G protein, Gs, produces adenyl cyclase and converts ATP to cAMP. AQP2 will be phosphorylated by the protein kinase A (PKA). The phosphorylated AQP2 (P-AQP2) will attach itself to the apical membrane and facilitate the reabsorption of water going back to the bloodstream. The final product will be concentrated urine (Qureshi, et al).

Like type 1 and type 2 diabetes mellitus, when there is a problem in the supply or the body’s reaction to vasopressin, diabetes insipidus arises.

There are 2 major types of diabetes insipidus – neurogenic or the central type, and the nephrogenic or renal type. Like diabetes mellitus, pregnant women may also suffer diabetes insipidus and this iscalled the gestogenic diabetes insipidus (“Diabetes Insipidus and Diabetes Mellitus”).

Figure 3 illustrates how water reabsorption in the body occurs.

The central type of diabetes insipidus is where little or not enough amounts of the antidiuretic hormone vasopressin are secreted from the pituitary gland. Because of this, there will be no substance to be attached to the AVPR2 receptor that is supposed to give the signal to the AQP2 to do its job. On the other hand, the renal type diabetes insipidus have enough amount of vasopressin but the body tends to have resistance in binding with the said hormone to facilitate the movement of the AQP2 to the apical membrane of the collecting duct cell in the kidney for the reabsorption of water from the urine (Qureshi, et al).

The third type, but considered to be rare, is the gestogenic diabetes insipidus. One of the side effects of the chemical reaction of the placenta in the body is the destruction of the vasopressin hormone. The degradation of the vasopressin is done by the vasopressinase or cysteine aminopeptidase. This usually occurs between the third trimester of pregnancy to the early postpartum period (Felman).

Diabetes is often related to blood sugar with the early signs or symptoms of excessive urination. However, there are two forms of diabetes – diabetes mellitus and diabetes insipidus. The urine in diabetes mellitus is sweet while in diabetes insipidus is very dilute or tasteless.

Both forms of diabetes are hormone-related. Insulin is secreted by the pancreas for diabetes mellitus while vasopressin is secreted by the pituitary glands for diabetes insipidus.

Diabetes prevalence in the Philippines is quite alarming. This only gives us the warning to keep our health monitored and choose a lifestyle that will keep us fit.

References:

Baclig, Cristina Eloisa. “Diabetes: A Bitter Health Crisis for Filipinos.” INQUIRER.Net, 21 July 2021, newsinfo.inquirer.net/1461980/diabetes-a-bitter-health-crisis-for-filipinos.

Bryant, Nia J., et al. “Regulated Transport of the Glucose Transporter GLUT4.” Nature Reviews Molecular Cell Biology, vol. 3, no. 4, 2002, pp. 267–77. Crossref, https://doi.org/10.1038/nrm782.

 

“Diabetes Insipidus and Diabetes Mellitus.” The Diabetic Voice.Com, www.the-diabetic-voice.com/diabetes-insipidus-and-diabetes-mellitus.html. Accessed 26 Apr. 2022.

 

Felman, Adam. “What’s to Know about Diabetes Insipidus?” Medical News Today, 7 Apr. 2022, www.medicalnewstoday.com/articles/183251.

 

“Glucose Regulation and Utilization in the Body.” Nutrition FN 225, media.lanecc.edu/users/powellt/FN225OER/Carbohydrates/FN225Carbohydrates5.html. Accessed 26 Apr. 2022.

 

“Insulin | Definition, Structure, and Function.” Encyclopedia Britannica, www.britanica.com/science/insulin.

 

Nelson, David. Lehninger Principles of Biochemistry. 7th ed., W.H. Freeman, 2017.

 

Qureshi, Sana, et al. “Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy.” Endocrinology, vol. 155, no. 12, 2014, pp. 4605–21. Crossref, https://doi.org/10.1210/en.2014-1385.

 

Tahrani, Abd A., et al. “Management of Type 2 Diabetes: New and Future Developments in Treatment.” The Lancet, vol. 378, no. 9786, 2011, pp. 182–97. Crossref, https://doi.org/10.1016/s0140-6736(11)60207-9.

 

Vasiljević, Jovana, et al. “The Making of Insulin in Health and Disease.” Diabetologia, vol. 63, no. 10, 2020, pp. 1981–89. Crossref, https://doi.org/10.1007/s00125-020-05192-7.

 

“What Is Diabetes?” Centers for Disease Control and Prevention, 2 Mar. 2022, www.cdc.gov/diabetes/basics/diabetes.html.

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Defective Glucose and Water Transport in Two Forms of Diabetes (Part 1 of 3)

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Just before the Diabetes Awareness Month ends, here is another series connected to this health issue. Previously, I shared how our tongue recognize the sweetness of the food we eat.

This is another topic in our reaction papers in Biochemistry. I divided this into three parts since the topic is quite long.

Defective Glucose and Water Transport in Two Forms of Diabetes (Part 1 of 3)

Many say that it is better to love men in their 40s. They are much sweeter compared to younger men. This is because many men in their 40s are diabetics. Diabetics are naturally sweet.

Diabetes, as defined by the Center for Disease Control and Prevention or CDCP, is a chronic health condition that affects the body’s ability to transform food into energy (“What Is Diabetes?”). Furthermore, Merriam-Webster defines diabetes as any abnormal condition described by excessive amounts of urine.

What is the Philippines' status when we speak of diabetes?

In 2019, according to International Diabetes Federation, the Philippines ranked 5th in the Western Asia Pacific region in terms of the numbers of diabetes prevalence with 3,993,300 individuals having the said ailment. This will be expected to increase in the next 25 years to about 7.2 million Filipinos. Because of this, Dr. Joven Cuanang considered diabetes to be an epidemic in the country (Baclig).

The common connotation of diabetes is blood sugar. There are two main forms of diabetes: diabetes mellitus and diabetes insipidus. Diabetes mellitus is the one connected with glucose absorption while diabetes insipidus is the condition with water reabsorption in the body.

Diabetes Mellitus

After eating, carbohydrates break into glucose and will stay in the bloodstream. The pancreas will secrete the hormone, insulin. When the insulin reacts with the insulin receptor, it will send a signal to the glucose transporter, GLUT4. GLUT4 is stored in the cell membrane as vesicles. This vesicle will move and fuse with the plasma membrane which will open the membrane at let the glucose enters the cell. Once the insulin level drops, GLUT4 will go back to the cell and will wait until it receives another signal (Nelson).

Figure 1. shows how the glucose in the blood reached the cell and use as a source of energy.

When the cell needed energy, the glucose will be metabolized thru cellular respiration and converted to ATP. Otherwise, it will be stored as glycogen in the liver and muscle cells, or as triglycerols or fatty acids in the adipose tissues (“Glucose Regulation and Utilization in the Body”).

If the problem occurs in the absorption of glucose arises, it will be referred Diabetes mellitus. There are 4 types of diabetes mellitus – Type 1, Type 2, gestational, and prediabetes.

If the pancreas is not supplying enough insulin to trigger the GLUT4, it will be called Type 1 diabetes mellitus. This is considered an auto-immune condition where the body mistakenly attacks the insulin in the body resulting in reduced or no secretion of insulin to trigger the GLUT4.

On the other hand, due to several factors, the body may develop insulin resistance and cannot trigger the receptor to signal GLUT4 to do its work. It is referred to as type 2 diabetes mellitus.

See the figures below for the differentiation of type 1 and type 2 diabetes in terms of insulin secretion and receptors.

Figure 2. Simple differentiation of type 1 and type 2 diabetes mellitus.

During pregnancy, a woman’s body is subjected to a diverse multitude of hormones and chemical reactions caused by the placenta. Because of this, the body may develop insulin resistance and may increase the blood glucose level. This condition is called gestational diabetes (“Glucose Regulation and Utilization in the Body”).

A person may have an increase in the blood glucose concentration up to the borderline towards the type 2 diabetes (blood glucose of 100-125 mg/dL) this is called prediabetic.

Glycolysis

Glycolysis is the process where glucose molecule is being breakdown and will be used by the cell as a source of energy. The glucose is broken down into pyruvate, a 3-carbon molecule. Upon entering the mitochondrion, this pyruvate will be converted to acetyl CoA which undergoes the Kreb cycle producing carbon dioxide and the high-energy electron carriers NADH2 and FADH2. After an electron transport by NADH2 and FADH2, ATP is released. If the cell has enough energy, the glucose will be used to synthesize glycogen or fat to be stored in the liver (“Glucose Regulation and Utilization in the Body”).

Figure 4. Glycolysis process of breaking down glucose as source of energy (ATP).

For the instances that there is not enough glucose in the body, which usually happens during starvation, the protein or the fatty acids will be utilized to produce the energy required by the cell. The protein will be converted to glucose by the process of gluconeogenesis. Fatty acids will be converted to ketones and this will be utilized as a source of energy. Between the two alternative sources of energy, our body will favorably proceed with the fatty acid utilization to conserve the protein (“Glucose Regulation and Utilization in the Body”).

Figure 5. An illustration of gluconeogenesis (conversion of protein to glucose) and fatty acids to ketones as alternative sources of energy.

Diabetes prevalence in the Philippines is quite alarming. This only gives us the warning to keep our health monitored and choose a lifestyle that will keep us fit.

 

References:

Baclig, Cristina Eloisa. “Diabetes: A Bitter Health Crisis for Filipinos.” INQUIRER.Net, 21 July 2021, newsinfo.inquirer.net/1461980/diabetes-a-bitter-health-crisis-for-filipinos.

Bryant, Nia J., et al. “Regulated Transport of the Glucose Transporter GLUT4.” Nature Reviews Molecular Cell Biology, vol. 3, no. 4, 2002, pp. 267–77. Crossref, https://doi.org/10.1038/nrm782.

 

“Diabetes Insipidus and Diabetes Mellitus.” The Diabetic Voice.Com, www.the-diabetic-voice.com/diabetes-insipidus-and-diabetes-mellitus.html. Accessed 26 Apr. 2022.

 

Felman, Adam. “What’s to Know about Diabetes Insipidus?” Medical News Today, 7 Apr. 2022, www.medicalnewstoday.com/articles/183251.

 

“Glucose Regulation and Utilization in the Body.” Nutrition FN 225, media.lanecc.edu/users/powellt/FN225OER/Carbohydrates/FN225Carbohydrates5.html. Accessed 26 Apr. 2022.

 

“Insulin | Definition, Structure, and Function.” Encyclopedia Britannica, www.britanica.com/science/insulin.

 

Nelson, David. Lehninger Principles of Biochemistry. 7th ed., W.H. Freeman, 2017.

 

Qureshi, Sana, et al. “Diabetes Insipidus: Celebrating a Century of Vasopressin Therapy.” Endocrinology, vol. 155, no. 12, 2014, pp. 4605–21. Crossref, https://doi.org/10.1210/en.2014-1385.

 

Tahrani, Abd A., et al. “Management of Type 2 Diabetes: New and Future Developments in Treatment.” The Lancet, vol. 378, no. 9786, 2011, pp. 182–97. Crossref, https://doi.org/10.1016/s0140-6736(11)60207-9.

 

Vasiljević, Jovana, et al. “The Making of Insulin in Health and Disease.” Diabetologia, vol. 63, no. 10, 2020, pp. 1981–89. Crossref, https://doi.org/10.1007/s00125-020-05192-7.

 

“What Is Diabetes?” Centers for Disease Control and Prevention, 2 Mar. 2022, www.cdc.gov/diabetes/basics/diabetes.html.

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