Factors that affect gallstone formation

Oral dissolution therapy

In traditional Malay medicine, people have tried taking blended juices of daun lidah jin and daun gajah beranak to help dissolve gallstones. But this may only work for small gallstones.

In modern medicine, there are 2 preps - Ursodiol (Actigall) and Chenodiol (Chenix). These medications contain bile acids that can dissolve small gallstones made of cholesterol. It may take months or years of treatment to dissolve all the gallstones.

Cholesterol gallstones form when there is an imbalance between the 3 major components of bile (biliary lipids) - cholesterol, phospholipids, and bile acids (please refer to phase diagrams).

Cholesterol gallstones are also attributed to prolonged large bowel emptying, large bowel transit time, LBTT, slow colonic transit, or prolonged intestinal transit (slow transit constipation).

So it all boils down to:

People who have short bowel transit time, and who do not have constipation, also do not develop gallstones, despite having high hepatic cholesterol or blood cholesterol.

External links:
http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/gallstones/Pages/facts.aspx
http://www.ncbi.nlm.nih.gov/pubmed/12570727
https://www.inkling.com/read/greenfields-surgery-scientific-principles-practice/chapter-60/figure-60-3
http://www.ncbi.nlm.nih.gov/pubmed/10982775

Healthline

Healthline is a website that contains useful health articles for everyone. It is useful for new medical students too. Many of the topics I have taught under Lipids and related topics can be found at this website. I hope you will visit and read its articles. It is also on Facebook. I hope students will widen their reference base and see the many options available at this website.

Prof Faridah
12 October 2014

External links:
http://www.healthline.com/health/cholesterol/effects-on-body
http://www.healthline.com/understanding-cholesterol/anatomy-animations#1/bodies-in-motion-cholesterol
http://www.healthline.com/directory/topics?ref=global

Effects of high blood cholesterol on the body

I have written the following cases based on true incidences. Try and understand the underlying pathology and explain them.


Case 1

The son of a 75-year old man frantically called a close friend to seek assistance for admitting his father to the hospital for heart disease (sakit jantung). His mother already passed away many years ago. Now his lonely father is unwell and needs urgent medical attention. His son feels intimidated and uncertain about what to do for his father's condition. He has no idea what the procedure is like if he decides to bring his father to hospital. He needs help before he will take his father to hospital.

Case 2

A 39-year old man was happily married and going about his daily routine at home. His beautiful young wife had delivered their #5 child a month ago. On Thursday, when he got up to enter the toilet, he collapsed. His wife quickly took him to hospital. He was assessed for heart disease, treated, and discharged home. On the way home, again he collapsed and his wife had to rush him back to hospital. This time he was warded over the weekend and more investigations needed to be done on him the following week. He felt intimidated. He was weak and exhausted. On Sunday morning, he called his friend/boss to inform him about what had happened since he could not come to work that day. With mixed feelings, his boss went to visit him in the ward.

Case 3

A 72-year old woman was driven around in her son's car and visited all her 7 children. She was happy and felt blessed. However, her married son (the driver) did not know that his diabetic mother had heart disease. He knew she was a diabetic. One day, he drove for 4 hours and they visited a Malay bomoh far out somewhere in the jungle. After that they drove home but stopped for lunch at a nearby restaurant. Exhausted from all the travelling and not eating her meals on time, the woman passed away at lunch time. The son was shocked.

Case 4
A retired school headmaster enjoyed cow's brain. Whenever he went to kenduri, he would go into the kitchen and ask if there was a cow's brain available. The ladies would dish out the cooked cow's brain and serve it on a platter, just for him. Sitting in the corner, he ate the entire cow's brain by himself. He died the following day.

Case 5
A 56-year old man had his blood profile done at the hospital where he worked. His blood profile was fine except for his cholesterol, which was a bit high. Upon learning about his blood cholesterol from a friend/senior scientist in the clinical laboratory, he felt he needed to do something about his blood cholesterol. He contacted some doctors for dietary modification. He started taking Bragg apple cider vinegar, twice daily. He ate fresh pomegranate, dried apricots and dried dates. He started taking oat bran but had to stop since it made him urinate too frequent. He stopped eating most of the food he had once craved. His food intake seems bland and unappealing to his wife. He skips meals to avoid putting on weight. His wife feels intimidated and does not know how to help him.

Case 6
A beautiful young woman in her mid-twenties got married to a dream man of her life. Unfortunately, he died of a heart attack while on duty overseas. He died 5 years into their marriage, at age 41. She was devastated. They had no children. She went on to marry another man but her second marriage failed and she had no children. She got married for a third time and but still had no children. Now in her mid-sixties, and without any children, she still misses her first husband.

Case 7
An illiterate mother of 7 and grandmother of 52 married at age 18. A pretty young slim lady, she stayed home to cook and look after the family while her husband worked. Without proper knowledge about diabetes, she overate and suffered from chronic diabetes. She was diagnosed of diabetes at age 31, following the birth of her last child. In her 40s, 50s, and 60s, her diabetic status worsened as diabetic complications appeared one after another. She was obese beginning in her 30s. She was easily tired, her vision was poor and her body was constantly in pain. Her knees would swell which further reduced her mobility. She was constantly in and out of hospital for fatigue and loss of appetite (LOA). In her mid-60s, she was confined to a chair from morning till night, hardly ever moving about in the house. She would call on her children or grandchildren for anything she needed, including her drink and insulin injection. She had an intraocular lens (IOL) installed for her badly clouded eye lens so she could see, but that also later failed her - she was apparently 'blind'.  She consumed local herbs and preparations to help control her diabetes. She had no diabetic sores nor lesions. Her skin was clean, smooth, and well-hydrated. However, she had a big scar from a previous boil on her buttock. She died of heart attack one morning in her son's lap, aged 65. 

Case 8
A illiterate mother of 12 suffered from stroke and was looked after by one of her daughters. In her young life, she had married at age 12 and stayed at home to look after her family. She sold satay as a source of income in her middle age and late life. Before the onset of her stroke, she was visiting her youngest daughter and had consumed 1 kilo of green sour mangoes which she craved. Then she went to bed for her afternoon nap (siesta). When it was time for her to wake up for her evening prayer, she could not move - stroke had struck her. Her children panicked. Nothing her children did could make her snap out of her stroke condition. As days passed, she became overly depressed. One of her daughters and family helped to nurse her for life - feeding her soft food and whatever they knew of her favourite foods. However, she refused to eat and lost weight - still depressed. She became angry with herself and refused to eat. With a big frame and a wasted body (still heavy), she died 2 years after her stroke, apparently still depressed.


Effects of cholesterol on the body:
http://www.healthline.com/health/cholesterol/effects-on-body
http://www.healthline.com/health/high-cholesterol?ref=global

Health24

Health24 is a useful website that has many simple articles and health calculators to help readers update themselves about their own health. It also features updates on many conditions that affect most of us as we age.

http://www.health24.com/Medical/Heart

Uses of Honey

Honey has many uses and purposes - culinary, health, medical and Sunnah.

Culinary
It is used in cooking to supplement or replace sugar. Honey is used for making a basting paste to obtain a shiny chicken skin when roasting, baking and making BBQ chicken or chicken satay. Honey is also used to sweeten hot drinks such as plain tea, lemon tea, hot cocoa, and many other hot drinks.

Health
Honey is used widely in healthcare products. It is used in soaps, shampoos, lotions, and creams.

Honey is an ingredient in baby milk formula. Even if a baby milk formula does not contain honey, it can be added while re-constituting the milk powder. Honey must not be given to babies under age 1 year as they cannot defend themselves against bacterial spores and toxins in raw honey. Honey for babies must be cooked - eg honey in cereals.

Honey is an ingredient in many Malay traditional healthcare products. Honey is mixed with warm water and cinnamon powder added to make a health drink. This is taken twice a day - once in the morning on an empty stomach, and again at night before sleep. This is supposed (believed) to get rid of all kinds of ailments, including heart disease, diabetes, and cancers - including brain and breast cancers.

Cold sweet honey-lemon drink, as served by Secret Recipe, is a good stopper for tummy upset and traveller's diarrhoea. One tall glass of cold sweet honey-lemon is sufficient to abruptly stop abdominal discomfort and travellers can then travel safely to their destinations. Airport cafes and good airlines should try and consider to serve this cold sweet honey- lemon drink to their clients.

Medical
Pure honey has been applied to help heal wounds following surgery. It only works when in the pure form. It contains hydrogen peroxide which will effectively kill bacteria.

Sunnah
For Muslims, honey is a food ingredient consumed by Prophet Muhammad SAW. Please refer to texts written by Muslim nutritionists, healthcare providers, researchers, and doctors on uses of honey.

External links
http://www.webmd.com/diet/features/medicinal-uses-of-honey

Interstitial Lung Disease (ILD)

An apparently healthy looking 8-month-old baby girl has been in hospital since birth. She was in Intensive Care Unit (ICU) for six months and was moved to the open ward since then.

She has lung and breathing problems. She has shortness of breath - she breathes short rapid breaths. The lungs dip at the apex on the skin surface as she breathes.

Interstitial lung disease is suspected (ILD). However, no lung biopsy is planned.

She is dependent on external oxygen supply and cannot go off oxygen supply for long periods, or she will become cyanosed. She can be propped up, but not for long.

Doctors advised the mother to have her name changed. The baby's name was changed since 3 babies shared the same name and the other two had died while in ICU.

She is fully breastfed on expressed breast milk (EBM). At 8 months, she is old enough and should be weaned off breastmilk and semi-solid food should be introduced.

She is the youngest of 6 siblings. The eldest and youngest being girls. The sibling before her is now 3 years old. The mother is 42 years old (peri-menopausal), and is number 5 of 9 siblings.

Where do we go from here?

External links:
http://www.webmd.com/lung/interstitial-lung-disease
http://www.onhealth.com/interstitial_lung_disease/article.htm

Prof 1 Viva 17July2014

Students who scored 70% marks and above, are called for a distinction viva. The viva panel consists of 3 lecturers, one from each discipline - Anatomy, Biochemistry, and Physiology. There are usually 27-30 A-students, and they are divided into 3 groups. There are 3 groups of panel examiners.

To obtain a distinction in the viva, students had to pass all 3 components of the viva - Anatomy, Physiology and Biochemistry. The panel must come to a unanimous verbal decision whether you get/don't get a distinction.

Group A panel comprised Prof Musalmah Mazlan (Biochemistry, External Examiner, UiTM), Dr Nurul Aiman Mohd Yusof (?) and Dr Liza Nordin (?). Observer: Dr Amida Mohd Safuwan.

Group B panel comprised myself (Biochemistry), Dr Mohd Asnizam Asari (Anatomy), and Dr Ainul Bahiyah Abu Bakar (Physiology). Observer: Dr Nazlahshaniza Shafin.

Group C panel comprised Dr Asma' Hj Hassan (Anatomy), Assoc. Prof. KNS Sirajudeen (Biochemistry), and Dr Che Badariah Ab Aziz (Physiology). Observer: Dr Md Rizman Md Lazim.

My panel interviewed 8 students and we decided not to give any distinction to any of our students as none met our expectations.


Anatomy 

1. Bone specimen. The bone specimen was 2 vertebrae. The students were asked various parts of the vertebrae and what lies in the spinal canal. 
2. Spleen. The students were asked relations to the spleen.

Physiology

1. Thyroid. The students were asked about the thyroid hormones, their syntheses and iodine deficiency. 
2. Goitre. The students were asked about the etiology of goitre.

Biochemistry

1. Macromolecules. There are 4 terms - biomolecules, macromolecules, micromolecules, micronutrients. Biomolecules are all the molecules in our body, ie biological molecules. Macromolecules are large molecules in our body, ie proteins, lipids, carbohydrates, and nucleic acids (DNA and RNA). Amino acids are monomers for proteins. Amino acids are not macromolecules, but proteins are. Fatty acids are components of triglycerides, phospholipids and cholesteryl esters. Fatty acids are not macromolecules, but triglycerides, phospholpids, and cholesteryl esters are. Nucleotides are components of nucleic acids. Nucleotides are not macromolecules, but DNA and RNA are. Micromolecules are small molecules in our body, ie glucose, amino acids, glycogen, acetyl CoA, pyruvate, citrate, etc. Micronutrients are substances that are needed in small quantities by the body, ie vitamins, trace metals, and essential fatty acids (EFA).
2. Metabolism. This time I asked about lipid metabolism (the other 2 choices are protein metabolism and carbohydrate metabolism). I asked about fat metabolism during fasting. Triglycerides are lipid storage molecules in adipose tissues found under the skin and spaces in between organs. There are 2 stages of how we obtain energy during fasting - an early stage and a latter stage. In the early stage, there is glycolysis and protein breakdown. In the latter stage, there is fat mobilisation and ketolysis as energy sources. I asked the students to start with fat mobilisation; some have problems recalling the processes for energy sources during fasting. Triglycerides are complex lipids; they need to be broken down first before the body can use it as an energy source. Triglycerides are hydrolysed by hormone sensitive lipase (HSL) in a stepwise fashion, first to diglyceride (DG), then monoglyceride (MG) and finally to glycerol (G) and free fatty acids (FFA). Fat mobilisation is the breakdown and movement of simple lipids (fatty acids and glycerol) from adipose tissue to the liver, via albumin as a carrier protein. Ketolysis is the breakdown of ketone bodies from muscle and liver, and subsequent oxidation of ketone bodies in the liver. In the long term, the body utilises FFA and ketone bodies as an energy source. Some students prioritised that brain prefers glucose as an energy source, and can't utilise ketone bodies because of the blood-brain barrier (BBB).
3. Hormones. I asked how is blood glucose controlled. Most answered by 2 hormones, insulin and glucagon. I then asked what are the actions of insulin. Some accidentally said insulin raised blood glucose! Most could answer well about the mode of action of insulin. I also asked about the action of glucagon. Many could not answer about action of glucagon. I think students don't know or can't recall that glucagon is considered a counter-regulatory hormone, ie its actions are the opposite of those of insulin. I asked what are the causes of diabetes. Some answered well, but some explained the pathophysiology wrongly. 
4. Cancer. I asked about cancer - causes (DNA mutation, uncontrolled mitosis), treatment (surgery, radiotherapy, chemotherapy), and anti-cancer drugs (enzyme inhibitors). I asked about causes of cancer and some students mentioned DNA mutation. I probed about the nature of the DNA mutation, how the mutation occurs and the nature of DNA damage. I asked if the mutations can be corrected or repaired. Many students talked about presence of repair system that corrected the mutation. Some answered something about the cell cycle, disrupted apoptosis and uncontrolled mitosis, leading to cell proliferation. I asked the students whether they have studied and know about enzymes. Some could hardly recall the enzymes. A few students managed to answer well about the 2 types of enzyme inhibition - competitive inhibition and non competitive inhibition.
5. Antioxidants. I asked about antioxidants - what they are and how they function. I asked what are antioxidants. I asked how free radicals cause damage. I probed about reactive oxygen species (ROS) and body's defenses. Some mentioned the antioxidants are glutathione system. Some answered lipid peroxidation affected lipid bilayers, biomembranes. I asked the significance of lipid peroxidation and related changes to lipid bilayer. Some mentioned lipoproteins and LDL oxidation. I asked about lipoprotein composition (PL, FC, CE, and TG). I asked about function of LDL. I asked about what happened to oxidised LDL (oxLDL). Some students mentioned LDL are easily oxidised to oxLDL, which cause plaque at the arterial endothelium, and lead to atherosclerosis (some said arteriosclerosis). I then asked what happened next after atherosclerosis. Some answered heart attack and (myocardial) infarction. Nobody mentioned stroke. Prolonged hyperlipidaemia leads to oxidation of LDL. Oxidised LDL (oxLDL) are small destructive particles as they can easily penetrate the arterial intima and cause harm. The macrophages consumed the oxLDL till they become foam cells and die, leading to changes in the arterial intima and underlying area.

Prof Faridah

Heme vs Hemin

1. What is heme?
A red inorganic molecule.
Is found in rbc.
Is found in hemoglobin (Hb) and myoglobin (Mb); there are 4 hemes in Hb, and 1 heme in Mb.
Carries oxygen by binding; 1 heme binds 1 oxygen molecule.
Makes rbc red.
Makes blood appear bright red.

2. What is hemin?
A black inorganic molecule formed by heme oxidation (exposure to air).
Is found when rbcs burst open (lysed, destroyed) and exposed to oxygen in the air.
Formed from heme upon long standing outside the body.
Is formed in vitro.
Makes blood appear dark.

3. Are heme and hemin the same?
No.
Heme is functional when present inside intact rbcs.
Hemin is non functional; it is a dysfunctional molecule.

Fresh blood is bright red due to presence of heme in intact rbcs.

Stale blood is dark or black due to presence of hemin. Heme converts to hemin. The longer exposure to air, and greater conversion to hemin, the darker the blood.

External links:
http://en.wikipedia.org/wiki/Hemoglobin
http://en.wikipedia.org/wiki/Myoglobin

Revision: Lipid Metabolism 1 July 2014

INTRODUCTION

LIPIDS topics are covered by 2 lecturers - Dr Win Mar Kyi (WMK) and myself (FAR). The topics have to fit into the number of slots allocated by the Phase I Committee, based on the Objectives submitted by the Department at Curriculum Reviews in the past. I only attended one Curriculum Review.

• Lipid Structure & Function (FAR) 
• Lipid Degradation (Fat Mobilisation); covered under Lipid Metabolism (FAR) 
• Ketogenesis (WMK) 
• Fatty Acid Synthesis; covered under Lipid Metabolism (FAR) 
• Triglyceride & Phospholipid Biosynthesis; covered under Lipid Metabolism (FAR) 
• Cholesterol (Steroid) Metabolism (FAR) 
• Lipoprotein Metabolism (FAR) 
• Integration of Metabolism

Lipid Metabolism is covered in 2 blocks in Phase 1 - Foundation and Endocrine.

In Foundation Black, I covered one topic: Structure and Function of Lipids (1 Oct 2013).

In Endocrine Block, I covered 4 topics:
1. Lipid Metabolism (30 April 2014)
2. Regulation of Lipid Metabolism (30 April 2014)
3. Lipoprotein Metabolism (4 May 2014)
4. Cholesterol Metabolism (4 May 2014)

From an applied standpoint, lipids are important because pesticides are fat-soluble and can accumulate in adipose tissues of the body. This phenomenon is referred to as biological magnification.
http://www.rsc.org/education/eic/issues/2007May/PesticidesKeepingOneStepAhead.asp

----------------------------------------------------------------

STRUCTURE AND FUNCTION OF LIPIDS 2013/14

Depending on how the lipids are grouped, the actual number of lipid classes may vary for different disciplines. In Chemistry, there are 9 LIPID CLASSES. However, we are only interested in a few classes which are of importance to Medicine.

1. Simple fatty acids – saturated, unsaturated 
2. Mono-, di- and triglycerides (triacylglycerols) 
3. Glycerolphospholipid (phosphoglycerides) / phospholipids eg. lecithin (phosphatidyl choline) 
4. Sphingolipids 
5. Steroids & Sterols eg. cholesterol 
6. Prostaglandins 
7. Lipid-soluble Vitamins & Precursors 

I don't teach all the lipid classes as some will be covered by other departments where the lipid classes have more relevance - Pharmacology and Physiology.

In Medicine, we are interested in only 4 LIPID CLASSES. The MAJOR TYPES OF LIPIDS are thus:
1. Triglycerides (neutral fats; comprise Fatty Acids and Glycerol)
2. Phospholipids
3. Sterols
4. Waxes (eg cerumen or ear wax)

---

CHARACTERISTICS OF LIPIDS

Examples of LIPIDS are oils, fats, waxes, phospholipids, and steroids. LIPIDS have distinct characteristics:

Principle elements: C, H, & O
Some with P & N
Water-insoluble
Soluble in solvents

LIPIDS contain carbon (C), hydrogen (H), and oxygen (O).
Additionally, some lipids contain phosphorus (P) and nitrogen (N).
LIPIDS are complex molecules composed of carbon, hydrogen, and oxygen, +- phosphorus and nitrogen.

LIPIDS are generally water-insoluble and do not mix with water - they are immiscible with water and remain afloat (terapung). However, LIPIDS are soluble in other solvents, eg acetone, chloroform, hexane, petroleum ether (PE), kerosene, and others.

Most lipids are non-polar and are hydrophobic because they contain hydrocarbon chains. Hydrocarbon chains contain carbon and hydrogen.

If there are double or triple bonds in the hydrocarbon chain, the lipids are said to be “unsaturated”

Like carbohydrates, LIPIDS are energy-rich compounds made from carbon, hydrogen, and oxygen, whose ratio is much less than 1:2:1.

Lipids include fats, oils, and waxes.

Lipids are non polar hydrocarbons.

When sufficiently close together, weak but additive van der Waals forces hold them together.

They are not polymers in the strict sense, because they are not covalently bonded.

Vitamins are small molecules not synthesized by the body and must be acquired in the diet.

Waxes are highly non polar and impermeable to water.

---

FATTY ACIDS

Fatty acids are non polar hydrocarbon with a polar carboxyl group.

Fatty acids are amphipathic: they have opposing chemical properties:

When the carboxyl group ionizes, it forms COO– (carboxyl group) and is strongly hydrophilic; the other end is hydrophobic and has CH3 (methyl group).

---

FATTY ACID NUMBERING SYSTEM

http://drbonesshow.com/links/fats.html

The first carbon in the figure above is called the carboxyl carbon (C=O) and it is where the fatty acid numbering system begins.

The first carbon after the carboxyl carbon is called the alpha-carbon and it is carbon number 2 of the fatty acid chain.

The beta-carbon is the second carbon after C=O and is located at carbon number 3 of the chain.

The last carbon atom in the chain is designated the omega-carbon, which is reflective of the fact that omega is the last letter of the Greek alphabet.

Look up the Greek alphabet.

---

SATURATED FATTY ACIDS & FATS

Saturated fatty acids (SFA) have carbon-carbon single bonds.

Unsaturated fatty acids have carbon-carbon double bonds.

Saturated fats contain mainly SFA compared to unsaturated fatty acids.

Unsaturated fats contain mainly unsaturated fatty acids compared to SFA.

Fats with only carbon-carbon single bonds are called saturated fats.

Butter and coconut oil are examples of saturated fats (oils).


Example:

Stearic acid is an 18-carbon (18C) saturated fatty acid.

Wikipedia

---

ESSENTIAL FATTY ACIDS (EFA)

Different molecules of fat have different fatty acid molecules attached to glycerol.

Most of the fatty acids we need to build fats can be created or "synthesized" by the body.

There are 3 fatty acids that cannot be made in this way and therefore they must be included in our diet.

The 3 "essential" fatty acids are linoleic acid, linolenic acid and arachidonic acid.

They are all unsaturated fatty acids.

http://drbonesshow.com/links/fats.html

---

COMPLEX VS SIMPLE LIPIDS

Glycerol is the main backbone upon which more complex lipids are built. Fatty acids are joined (esterified) to glycerol by ester bonds, to form triglycerides (also called triacylglycerols). Glycerol and fatty acids are simple lipid molecules. Triglycerides are considered as complex or simple lipid molecules, depending on who is doing the talking. In most textbooks, triglycerides are considered as complex lipid molecules. However, there are a few scientists who choose to look at triglycerides as simple molecules.

GLYCEROL

Glycerol has 3 carbons.
Glycerol contains 3 —OH groups, one at each carbon. (—OH is an alcohol functional group)
Glycerol is consumed in glycolysis.
Glycerol is sourced from the breakdown of triglycerides in adipose tissues (during fat mobilisation)
Glycerol is carried by albumin in blood and delivered to liver.

FATTY ACIDS

Fatty acids are non polar hydrocarbons with a polar carboxyl group at one end and a methyl group at the other end.

The fatty acid carboxylic group bond with the hydroxyl groups of glycerol in an ester linkage (ester bond).

The fatty hydrocarbon backbone consists solely of carbon atoms with hydrogen as side group.

Examples:

The minimum number of carbon atoms in a fatty acid backbone is 4 (in butyric acid).

Wikipedia

Eicosapentaenoic acid (EPA) is a long fatty acid and has 20 carbon atoms in its backbone. It has 5 carbon double bonds, beginning at the 3rd omega carbon (n-3), counting from the methyl end). It belongs to the omega-3 class of fatty acids.

The maximum number of carbon atoms in a fatty acid backbone is 22 (in docosahexaenoic acid, DHA). It has 6 carbon double bonds beginning at the 3rd omega carbon (n-3).

TRIGLYCERIDES

Fats and oils are triglycerides (simple lipids), composed of fatty acids and glycerol.

One glycerol plus 3 fatty acids make a triglyceride:

A saturated triglyceride contains mostly saturated fatty acids.

An unsaturated triglyceride contains mostly unsaturated fatty acids.

Different fatty acids can bind to the same glycerol molecule, giving rise to a mixed triglyceride (mixed fat).

A mixed triglycerides contains both saturated and unsaturated fatty acids.

---

SATURATED FATTY ACID (SFA) VS. UNSATURATED FATTY ACID (UFA)

A. Saturated Fatty Acids (SFA)

Saturated fatty acids (SFA) do not contain double bonds between carbons—they are saturated with H atoms.

Examples:

(i) Butyric acid

Butyric acid has 4 carbon atoms in its backbone and no carbon double bond (C4:0). It is the simplest saturated fatty acid. It is also the shortest saturated fatty acid. It is a main component of butter. Butter is solid at room temperature but melts easily at higher temperatures. Butter is unstable and breakdown to produce free butyric acid, which gives butter its rancid odour. Old butter and biscuits smell rancid when the butter in them breakdown to yield butyric acid; the more advanced the breakdown, the more rancid the odour.

 

(ii) Palmitic acid

Palmitic acid has 16 carbon atoms in its backbone and has no carbon double bond (C16:0). It is a saturated fatty acid found in palm oil, which is extracted from the fruits of the oil palm. 

Wikipedia

(iii) Stearic acid

Stearic acid is a saturated fatty acid with 18 carbon atoms in its backbone and no carbon double bond (C18:0). It is found in coconut oil.

B. Unsaturated Fatty Acids (UFA)

Unsaturated fatty acids (UFA) contain some double bonds in the carbon backbone. They are grouped into 2 types, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA).

1. Monounsaturated fatty acids (MUFA) contain only one C=C double bond.

2. Polyunsaturated fatty acids (PUFA) contain more than one C=C double bonds.

Examples:

(i) Oleic acid

Oleic acid is a monounsaturated fatty acid (MUFA), and has only one carbon double bond. Olive oil is an unsaturated oil containing oleic acid. Pure olive oil contains oleic acid in addition to other fatty acids. Virgin olive oil contains 99% oleic acid. Keeping virgin olive oil for some time will make it impure.

(ii) Palmitoleic acid

Palmitoleic acid has 16 carbon atoms in its backbone and a single carbon double bond (C16:1). It is a monounsaturated fatty acid (MUFA).

Wikipedia

---

SATURATED FAT VS, UNSATURATED FAT VS. MIXED FAT

A saturated fat is where the carbon atoms are surrounded by as many hydrogen atoms as possible.

An unsaturated fat has fewer hydrogen atoms than it could have.

A mixed fat has both saturated fatty acids and unsaturated fatty acids.

Example:

1-Stearoyl, 2-linoleoyl, 3-palmitoyl glycerol is a mixed triglyceride (mixed fat). It contains 3 fatty acids - stearic acid. linoleic acid, and palmitic acid.

---

BENDING IN UNSATURATED FAT MOLECULES: EFFECTS ON PACKING & FORM

A. Tight packing in saturated fats forms solid at RT

If the hydrocarbon chains are saturated with hydrogen, the fatty acid chains are straight and pack themselves close together forming a solid at room temperature (eg animal fat).

Examples:

Most animal fats are saturated and solid at room temperature, eg. butter, tallow, ghee, lard

B. Loose packing in unsaturated fats forms oils at RT

When double bonds form in hydrocarbon chains they cause the long hydrocarbon chains to bend.

In unsaturated fats, presence of one or more double bonds between carbons distort packing; prevent the fatty acid molecules from being able to “stack” or “pack” themselves tightly. Thus, they remain in a liquid state at room temperature (eg vegetable oils). 

Examples:

Most plant oils are unsaturated and liquid oils at room temperature, eg sunflower oil, rapeseed oil, corn oil, palm oil

---

Monoglyceride

A monoglyceride is formed and water is eliminated when a fatty acid combines with glycerol. The fatty acid joins the glycerol via an ester bond (-C-O-C-). When a monoglyceride is boiled (or acted upon by an esterase enyme), the ester bond is broken, resulting in a glycerol and a free fatty acid.

Diglyceride

A monoglyceride combines with a second fatty acid to form a diglyceride, with the elimination of water. The second fatty acid combines at the third carbon position (C3), leaving the second carbon hydroxyl undisturbed. A second ester bond forms at this third carbon. There are 2 ester bonds in a diglyceride, one at C1 and the other at C3.

Triglyceride

A diglyceride combines with a third fatty acid to form a triglyceride, with the release of water. The third fatty acyl chain combines with the hydroxyl at C2. The glycerol moiety now has 3 ester bonds, and forms a polar region. The fatty acyl chains are hydrocarbon chains which are hydrophobic - this region forms the apolar region. Identical or dissimilar fatty acids can combine with glycerol. A mixed triglyceride has different fatty acids. A saturated triglyceride contains all 3 or 2 saturated fatty acids, and is referred to as a saturated fat. An unsaturated triglyceride contains all 3 or 2 unsaturated fatty acids, and is referred to as an unsaturated fat.

Step-wise hydrolysis of triglycerides

Triglycerides are hydrolysed (broken down in aqueous medium and requires water) in a step-wise manner, first to form diglyceride, and then diglyceride to monoglyceride, and finally monoglyceride to glycerol and free fatty acid. Altogether, one triglyceride hydrolyses to one glycerol and 3 free fatty acids.

Hydrolysis of triglycerides by HSL in adipose tissue

In adipose tissue, the enzyme hormone sensitive lipase (HSL) hydrolyses triglycerides before stored fats can be mobilised from adipose tissue.

Fat mobilisation

Fat mobilisation is an important aspect of the regulation of fat metabolism. Fats from adipose tissue are mobilsed during fasting. Plenty of free fatty acids are carried in blood bound to albumin. This gives rise to the presence of high free fatty acid levels in blood. These free fatty acids are brought to the liver.

Fates of fatty acids in the liver

Fatty acids are taken up by liver cells (hepatocytes). The free fatty acids are first activated to from fatty acyl CoA and are then brought into the mitochondrial matrix by the carnitine transport system. Carnitine carries the activated fatty acyl chain into the mitochondrial matrix. Carnitine then dumps the fatty acyl CoA and carnitine is recycled to bring in more fatty acyl CoA.

Burning fatty acids in the liver (by beta-oxidation)

Fatty acids are broken down in a process called beta-oxidation. Please read up and obtain details of beta-oxidation from any clinical biochemistry textbook.

---------------------------------------------------

Endocrine Block 2013/14

In Endocrine Block, I covered 4 topics:

1. Lipid Metabolism (30 April 2014)
2. Regulation of Lipid Metabolism (30 April 2014)
3. Lipoprotein Metabolism (4 May 2014)
4. Cholesterol Metabolism (4 May 2014)

---

Practice MCQs

LIPID METABOLISM

1. Regarding lipid metabolism:
A. Activation of fatty acids requires ATP.
B. Carnitine transfers intact free fatty acids.
C. Hormone-sensitive lipase (HSL) degrades triglycerides.
D. Albumin transports plasma free fatty acids.
E. Fatty acid synthesis requires acetyl CoA.

2. Regarding lipid metabolism:
A. Synthesis of palmitic acid involves a multi-enzyme complex.
B. Beta-oxidation of fatty acids produces acetyl CoA.
C. Fat mobilization reduces triglycerides in adipose tissue.
D. Lipolysis involves a lipase.
E. Esterification involves an esterase.

REGULATION OF LIPID METABOLISM

3. Regarding regulation of lipid metabolism:
A. Fasting hydrolyses adipose triglycerides.
B. Starvation causes fat mobilization.
C. Insulin promotes fat storage.
D. Pregnancy reduces body fat.
E. Strenuous exercise depletes body fat.

4. The following reduce body fat:
A. Fasting.
B. Strenuous exercise.
C. Pregnancy.
D. Insulin.
E. Glucagon.

LIPOPROTEIN METABOLISM

5. Regarding lipoprotein metabolism:
A. Chylomicra (CM) transport dietary cholesterol in blood.
B. Very low density lipoproteins (VLDL) are precursors of IDL.
C. Hepatic (B,E)-LDL receptors clear low density lipoproteins (LDL).
D. High density lipoproteins (HDL) remove excess phospholipids.
E. VLDL participate in reverse cholesterol transport.

6. Regarding lipoprotein metabolism:
A. Lipoprotein lipase (LPL) hydrolyses triglyceride-rich lipoproteins.
B. Lecithin: cholesterol acyltransferase (LCAT) esterifies cholesterol.
C. Hepatic lipase (HTGL) removes triglycerides from lipoproteins.
D. Acyl cholesterol acyltransferase (ACAT) stores cholesteryl esters.
E. Cholesteryl ester transfer protein (CETP) exchanges lipids between lipoproteins.

CHOLESTEROL METABOLISM

7. Regarding cholesterol metabolism:
A. HMG-CoA reductase is the rate-limiting enzyme in cholesterol synthesis.
B. Cholesterol is synthesized selectively in the liver.
C. All human cells contain cholesterol.
D. Cholesteryl ester is absorbed in the small intestines as free cholesterol.
E. Cholesterol is excreted as bile acids.

8. Regarding cholesterol metabolism:
A. High HDL predisposes to increased heart problems.
B. High LDL cholesterol narrows the arterial lumen.
C. Blood cholesterol levels shift widely during a day.
D. High apoB levels indicate markedly increased LDL in the blood.
E. LDL cholesterol levels are treated in hyperlipidaemia.

 
Essay

Describe the endogenous lipoprotein pathway with aid of a diagram.
(10 minutes/10 marks)

Proposed Model Answer

Diagram:
(draw a labeled diagram)

Text:

	Statements	Marks
1.	Endogenous pathway happens all the time.	½
2.	It involves VLDL-LDL metabolism or “LDL cascade” and LDL receptor-mediated uptake in liver.	½
3.	Synthesis of VLDL:
4.	The liver synthesizes VLDL. Hepatocytes release nascent VLDL into the Space of Disse àVLDL enter sinusoid à VLDL enter systemic circulation.	½
5.	VLDL have several fates:
6.	a)      VLDL transport triglycerides from liver to peripheral tissues for utilization.	½
7.	b)      When VLDL reach vascular/capillary beds, they undergo hydrolysis (lipolysis) by LPL where their triglycerides contents are hydrolysed to free fatty acids (FFAs) and glycerol.	½
8.	c)      VLDL remnants are taken up by liver via LDL (B,E) receptors.	½
9.	d)     The VLDL are reduced in size and are converted into VLDL remnants and IDL, as a result of lipoprotein lipase (LPL) activity or delipidation.	½
10.	Unesterified FFAs have several fates:
11.	a)      During lipolysis, some FFA can be carried by plasma albumin and dispersed in plasma for delivery to other cells. Not much of this happens.	½
12.	b)      Normally, FFA can enter underlying adipocytes by simple diffusion. Inside the adipocytes, the FFA are re-esterified to form triglycerides (TG) once more. Adipocytes store TG until required (as an energy source during fasting or starvation). A majority of FFA are stored in adipocytes following lipolysis.	½
13.	c)      In times of starvation, when blood glucose is low and glycogen reserves are low, triglycerides stored in adipose tissues are hydrolysed by hormone sensitive lipase (HSL) and the FFAs are released from adipose tissue. FFAs then attach to circulating albumin and are brought to liver for beta-oxidation, for continued energy supply.	½
14.	IDL have several fates:
15.	a)      IDL can be converted into LDL by LPL in blood (intravascular).	½
16.	b)      IDL can be taken up by hepatic receptors.	½
17.	c)      IDL can be converted into LDL by hepatic lipase (HTGL) in liver.	½
18.	LDL have several fates:
19.	a)      Normally, LDL are taken up by hepatic LDL (B,E) receptors. The contents of LDL are broken down into FC, CE, PL, TG/ DG/ MG/ FFA and amino acids. These are kept within the hepatocytes or recycled for use by other cells. Hepatic contents of FC and CE are regulated by acyl cholesterol acyltransferase (ACAT). Few things can happen if cholesterol is low, specifically in the cell or in the blood. If there is low cellular FC, stored cholesterol (as cholesteryl ester, CE) is broken down to free cholesterol (FC) by ACAT. If there is low plasma FC, the liver cell makes more FC via increased HMG-CoA reductase activity. The 2 enzymes, ACAT and HMG-CoA reductase, are sensitive to cellular and blood cholesterol levels, and combined, they regulate cholesterol levels in cells and blood.	½
20.	b)      LDL can also deliver its contents directly to cells, eg adrenal glands, for synthesis of steroid hormones.	½
21.	c)      Under abnormal levels of LDL in the blood (eg hyperlipidaemia), LDL can be taken up by the scavenger receptors present on extrahepatic tissues (EHT).	½
22.	d)     LDL apoB-100 will be oxidized due to the prolonged presence of LDL in the blood. Also, the LDL particle is now smaller and apoB-100 is not stable at this stage. ApoB-100 becomes easily oxidised. Oxidised apoB-100 has higher affinity for macrophages. Thus, oxidised LDL will be taken up by macrophages in EHT.	½
23.	e)      Macrophages contain scavenger receptors on their surface. Macrophages are present on blood vessel walls. Oxidised LDL will attach to the receptors and be internalised.	½
24.	f)       The oxidised LDL are hydrolysed into component cholesterol, fatty acids, glycerol and amino acids, which are stored within the macrophages.	½
25.	g)      This uptake of oxidised LDL is unregulated (ie, not controlled). The macrophages take up as much LDL until they stop functioning and die off, becoming foam cells.	½