Saturday 28 May 2011

Problems faced by students and errors made on acid-base exams

EXAM TIPS & FEEDBACK

The questions covered in the SGD reflect what can possibly appear on exams. Past exam questions are made available to students in this section for self-study purposes. Since some questions are used repeatedly in exams, students are advised to try and answer them whenever time permits. The more students are acquainted with answering these questions, the more prepared they will be in upcoming exams. However, answering these questions does NOT guarantee that you will pass future exams. A lot will depend on how much you actually understand about the topic, underlying and related pathophysiology and compensatory mechanisms.

Year
Question
Time
2002/3
?

2003/4
ABG: Interpret the acid-base status & compensation:
pH 7.29, pCO2 50 mmHg, [HCO3-] 25 mmol/L
10 min.
2004/5
Describe the mechanisms of hydrogen ion excretion by the kidney.
15 min.
2005/6
Describe the role of the respiratory system in acid-base homeostasis.
15 min.
2006/7
No essay question

2007/8
No essay question

2008/9
?



Problems faced by students and errors made on acid-base exams

Problems encountered by students during exams and errors & inconsistencies discovered by examiners are highlighted in this section so that students become aware of persistent problems when learning this topic and work around them. It is hoped that students do not repeat these same mistakes in future.


General mistakes: Poor English, flow of answers & reasoning, haphazard answer, poor handwriting, untidy, misspellings, use of red/pink ink

1.      Need to improve English in order to write meaningful sentences.
2.      Not organized and writing begins all over the page. Cramped writing.
3.      Poor handwriting makes it difficult to mark answer.
4.      Sub-headings are not underlined, not properly numbered or not indicated.
5.      Too many cancelled words and changes in text make reading difficult.
6.      A large portion of text is crossed out (cancelled) on every page.
7.      Cancelled portion of graphs.
8.      Equations are not properly written or are not labeled. Unclear terms used.
9.      Answer written is not applicable (does not answer the question, irrelevant).
10. Terrible disjointed flowcharts. Or no diagram.


Category 1: Acid-base symbols, equations, equilibriums, imbalances, shifts, relationships between HH terms and acid-base changes in blood

1.      Unsure of symbols, inventing new but meaningless symbols: PHCO3-, [PCO2]
2.      Problem understanding equilibrium shifts (how & why, right shift, left shift).
3.      Unsure of terms used in the Henderson-Hasselbalch (HH) equation.
4.      Buffer ratio: Wrong primary lesion with wrong compensatory mechanism.
5.      Wrong statements about HH equation and equilibrium shifts.
6.      Wrong spelling: alkolisis, respiratory alkolisis
7.      Undecided which terms to use to describe specific changes: decrease vs. increase, low vs. high, normal vs. abnormal, partial vs. full, increase vs. decrease toward normal
8.      Contradictory relationship: Alkaline load causes ↓pH; pH↑ due to [H]↑
9.      False statement: When the pH in blood increase, the concentration of the H+ ions will increase.


Category 2: Acid load, alkali load, ingestion, intake, uptake

1.      Long definitions.
2.      Incorrect words: intake vs. uptake.
3.      Vague descriptions:
  • increase uptake of acid
  • in acidic situation
  • increase uptake of alkaline food
  • during hypoxia and acclimatization.
  • When someone ingest the acidic food.


Category 3: Problem understanding concepts & definitions on ventilation (hyperventilation, hypoventilation) and relating them to acid-base changes

1.      Unable to grasp the meaning of exhalation and inhalation.
2.      Unable to relate role of lung to PCO2 changes in blood.
3.      Misunderstands ventilation. Incorrect concept about PCO2 and ventilation.
4.      Wrong statement about the effect of hypoventilation on PCO2.
5.      Vague statements:
  • prevent loss of CO2 by respiratory mechanism.
  • Increase loss of CO2 by respiratory mechanism.
6.      Conflicting statements:
  • ↑HCO3- in metabolic acidosis;
  • ↓HCO3- in metabolic alkalosis.
7.      Wrong compensatory response in hyper- & hypoventilation.
8.      Wrong primary lesion with wrong compensatory mechanism.
9.      Order of compensatory mechanisms is reversed.
10. Descriptive terms for blood are carelessly used for lung action.


Category 4: Problem understanding chemoreceptors

1.      Jumble up chemoreceptors (central & peripheral).
2.      Incorrect detection of substances by chemoreceptors.
3.      Problem relating ventilation with suppression & stimulation of chemoreceptors.
4.      Sequence of events following stimulation of chemoreceptors.


Category 5: Wrong answers

1.      Answers on Rbc metabolism instead of respiratory system.
2.      Answers on renal instead of respiratory system.
3.      Answers on hypokalaemia & hyperaldosteronism instead of respiratory system.

Prof Faridah

Thursday 26 May 2011

How to adjust learning techniques

Dear Year 1 Medic Students,

You may have already developed your own learning style which you are comfortable with. But you have to know that your learning style is somewhat relaxed and not rushed. You learn slowly.

However, when you come into the university to study medicine, you will need to readjust and try to learn faster as you have a lot to read, understand, assimilate, see the whole picture, and try to see the relevance.

Since there is so much to learn in first year medicine, the best way to learn is therefore to develop a systematic and faster way to acquire information for better understanding and retention, and overview. Then to fit in as much new information into your skeletal framework. Only then can you advance very fast with reading and learning at the same time. Never fall behind in your reading and learning.

To start you off in the right direction, you must look after your health. This means you must try and develop a safe and yet healthy dietary routine that takes care of your health while you study. That diet must be a rich diet that supplies you all the nutrients and vitamins you need. You must have adequate iron in your hemoglobin.

Your dietary menu must contain a lot of fruits and berries, fresh and cooked vegetables, sufficient chicken or beef. You must drink sufficient fluid, be it water, fruit juices or milk. Fruit choices can be bananas and apples or other.

Eat a good healthy breakfast very early in the morning and empty out before you go to class. Drink a lot of fluids when you are on campus, especially in hot weather. With adequate fluid intake, your alertness is at maximum, and you can pay attention well to what is being taught. If you read ahead of time before each class topic, you should be able to understand each lecture fairly well. There will be gaps in your knowledge while in class and you can jot down the important words you heard but did not understand. Use the Internet to find out what they mean or relate to.

In your free time, use the Internet Google Images to search for relevant illustrations to help you learn. Almost everything taught in medicine today has relevant pictures on the Internet. Download those images and keep them in a folder named IMAGES (separate from your photos). Keep searching and downloading relevant images whenever you see some good ones. These images are very useful when you are unsure or confused about something that you learned. Go through the images when in doubt. Find more images if you need to.

When you read prescribed pages in your textbook for homework, read but at the same time use a pencil to jot down notes at the sides of each page. Go through your own notes to see if they make sense to you. These jotted notes are very useful when you do revision as you won't need to read all the pages again but just the jotted notes at the sides. Thus revision is speeded up.

Read up before class and read again after lecture. Never leave revision till Revision Week, as you won't have sufficient time to revise everything. Revise everyday and every night, all the time. Go through your notes over and over again till they make sense to you. If they don't make sense to you, it means that you didn't understand well and you need assistance. You can ask your roommates or in the next lecture.

If you are shy to ask something in class via the microphone, you can scribble on little pieces of paper and leave them on the lecturn (the lecturer's table up front) or place them in a box and put the box on the lecturn for the lecturer to answer your questions. Never refrain from asking. You will gain a lot by asking lecturers in this way rather than keeping quiet and not asking in class. Always ask the lecturer while he/she is still in the lecture hall. You can still run after the lecturer after class but most lecturers are tired after their lectures and sometimes this will irritate them.

If you have additional questions after class, you can e-mail direct to the lecturer concerned or write in the Forum in MedLearn. This e-learning Forum is under utilised and students tend to lose out. You must try and ask questions in MedLearn Forum

Some students join their lecturers' groups in Facebook and ask questions there. This is alright is your lecturer has a Facebook account and is willing to answer your questions in Facebook. Remember, Facebook is a social medium and is more meant for meet & greet new friends and relatives. It is not much used for learning. However, keep this option open because it is a more relaxed way to ask lecturers questions about your lectures. Ask your lecturers if they have Facebook and whether they are willing to answer your questions in Facebook. Facebook is strictly banned during office hours.

When you read or study, have a stack of scrap paper ready to jot down words or notes. You can cut used A4 paper and tie with a rubber band into a stack. You can buy colourful Post-It flags from Kedai Mahasiswa USM (RM6.00) to bookmark important pages as you read your textbook. That way you can keep track of important pages and diagrams for fast revision.

After you finished reading, you can use your laptop to prepare additional PowerPoint (PPT) presentations. These will help you to retain better as they serve as flash cards. You can narrate and add to your PPT to make a multimedia presentation.

There are many YouTube videos now that cover almost everything that is taught in medicine. Download then at home and bring to campus. YouTube is strictly banned during office hours.

There are many blogs which are opreated by medical students. They may be useful for you for learning purposes.

Whatever means you choose to study, make sure you feel comfortable and it is not burdening you. Adjust and readjust till you find a style that you like and will work for you. Develop a style that you can use for a lifetime and that needs little modification or adjustment. Try out a style for some time and if it works well for you, use it for your entire medical study and for life.

Prof Faridah

Friday 20 May 2011

Failed Year 1 Medicine

Dear Year 1 Medic Students,

Failing exams is part of the long learning process. Everyone fails at some point in the learning process. However, there are a few brilliant souls who have never failed in all their formal lessons, Alhamdulillah.

For medical students who have completed the entire one-year study of year 1 Medicine, you have actually gained a lot in terms of knowledge. It is very precious knowledge. Please keep that knowledge.

For those of you who passed year 1 first professional exam, congratulations for you can automatically proceed to year 2. It doesn't mean that you are smart and fit for year 2 and don't have to do anything. Quite the contrary as you will find out soon!

For those of you who failed the first professional exam, you are allowed to repeat the entire first year study when the next academic session opens in September 2011. All is not lost. You still have a chance to re-take the first professional exam in May 2012. I would suggest that you put in more effort into your learning, or adjust your learning techniques. I will write more about how to adjust learning techniques in my next post.

Prof Faridah

Thursday 19 May 2011

Professional 1

Dear Year 1 Students,
I am deeply grateful to Mei Xuan Ooi for asking me questions in Facebook message. I have reproduced her messages here so we can share. If students don't ask, there is no way lecturers will know. Of course any student can ask me questions in MedLearn, Facebook, e-mail, SMS, and this blog. The only problem with Facebook is I cannot view it at work. I have to go home to view questions from students in Facebook. Sometimes I don't check my Facebook and the questions remain unanswered for very long. It doesn't mean I don't wish to answer questions from students.
If the questions are good, I will copy & paste your questions here in my blog so they will benefit all other students. But I can only answer for the lectures I taught you. 
Other lecturers have their own blogs to help students. You must ask the other lecturers too. There was a good Physiology blog by Dr Mazlynn Mazlan (?). She already left USM but her blog is open to students worldwide. I will post her link in my blog if I find her blog again.

TQ
Prof Faridah

QUESTIONS FROM FACEBOOK

Mei Xuan Ooi27 April 21:19
Subject: Professional 1
Prof, sorry to disturb, Just wanna ask prof's lecture notes of lipid, U stated before we just need to read on HDL, Endogenous and exogenous, right? Mostly it will be out in SEQ, right? Then do we need to study the others except three of this? Will others (come) out in MCQ? Cause really a lot to memorize and we are lack of time. =( Thx prof :)

Mei Xuan Ooi27 April 23:34
Re: Professional 1
Okay, terima kasih Prof. Another question : Is the shuttle system like malate aspartate important? And will they ask us to count the ATP number, NADPH no and so on? Anyway, such a nice blog prof have. keep on writing ya. Terima Kasih :)

Wednesday 18 May 2011

Distinction Viva

To obtain a distinction, you had to pass all three components of the viva - Anatomy, Physiology and Biochemistry. The panel must come to a unanimous decision whether you get/don't get a Distinction. My panel comprised Dr Zul Izhar (Anatomy), Dr Ang Boon Suen (Physiology) and myself (Biochemistry). My panel interviewed seven students and we decided to give a Distinction to only the first Chinese girl.


Anatomy 
  1. Bone specimen. The bone specimen was the left clavicle in my group (humerus in the other groups). You had to figure out whether it was the right or left bone and support your answer with a description of the bone - why you thought it was the left bone and not the right bone. You had to name the ends and attachments of the bones. Some students weren't sure whether it was the left or right bone. Most gave the wrong answer! Most cannot describe as they couldn't figure out whether it was the right or left bone. Please review your Anatomy.
  2. Ootic nerve. Dr Asma' Hassan covered this topic to great length in her Revision Lecture. I was there in the lecture hall when she reviewed the ootic nerve.
  3. Cranial nerve
  4. Ciliary ganglion
  5. Parasympathetic and outflow
  6. Postganglionic
  7. Sigmoid sinus
  8. Muscles of mastication

Physiology
  1. Exercise. The scenario posed by Dr Ang was exercise. The questions asked evolved around exercise.
  2. Organ system. Dr Ang asked what systems are affected by exercise. Most students answered correctly, ie the respiratory system and cardiovascular system.
  3. Respiratory system. Dr Ang asked what changes occur in the respiratory system during exercise. Answers were correct in most cases except for those who didn't know the answer. Other questions were ventilation rate, perfusion-diffusion during exercise and venous return.
  4. Cardiovascular system. Dr Ang asked what changes occur in the cardiovascular system during exercise. Answers were a bit slow (shaky, unsure). A lot of students just guessed the answer! Dr Ang even asked what is the maximum pulse and heart rate, and whether there was a formula for maximum heart rate. Other questions were cardiac output.
  5. Physical. To give you a better picture, visualise (just imagine) what happens if you do exercise. Will you breathe harder? Why? Can you explain it? What happens to your pulse, heart rate etc? Why? Can you explain the changes?

Biochemistry
  1. Diabetes mellitus and hyperglycaemia. Questions were How is blood glucose controlled. Most answered Endocrine via insulin and glucagon. I then asked What are the actions of insulin? Most could answer. For hyperglycaemia I asked re how blood glucose can be elevated to such high levels. I asked What are the causes of hyperglycaemia? I was asking for the causes and most of you could give a list of possible causes, which was good.Some of you could name the sources of hyperglycaemia - high intake & low intake. Insulin receptors on cell surfaces were not responding to insulin. I asked the effects of high blood glucose. I was expecting glycation, eg glycated hemoglobin (HbA1c or A1C) and AGE (Advanced glycation products) but nobody answered those. 
  2. Hyerlipidaemia. Then I asked re hyperlipidaemia and what were the possible causes. I asked What are the causes of hyperlipidaemia? Some took ages to answer about causes of hyperlipidaemia. I asked about the role of lipoprotein lipases (LPL) and some of you could answer alright. I asked re LDL, LDL cascade and role of LDL. I asked how high numbers of LDL behaved in prolonged lipaemia. Most could not answer. The correct answer is 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 of the artierial intima and underlying area.
  3. Free radicals and antioxidants. I asked you to define free radicals and antioxidants. I asked What are free radicals/antioxidants? I asked you what would happen if free radicals won over antioxidants. I asked you to give examples of free radicals and most just answered simply. I then asked How do free radicals cause damage? Some answered all right. I then asked What are cellular defense systems? Some were able to answer - the glutathione system, etc.
  4. DNA mutation. I asked you where mutations occurred in the cell. Most answered correctly, within the DNA structure. I asked How does DNA damage occur? Some were able to describe what went wrong at some stage in the cell cycle. I asked whether there are repair systems that can repair mutations as they occurred in the cell. And most students could answer.
  5. Cancer. I asked what was the general scientific basis for understanding cancers. I asked How does cancer occur? Most of you just memorised and blurted. It would be better to understand and try to explain slowly but clearly.

Congratulations to the two Chinese medical students who obtained Distinction for their first-year studies. Here are the names of the two medical students: Kwa Schee Li (female) and Tan Fo Yew (male).

I remember Kwa Schee Li. She was the first person to be interviewed by the panel which I headed. She was calm, well-composed and fluent with her answers. To me, she was appropriately dressed as a medical student. She knew her subject matter well and the three of us who interviewed her agreed she deserved a Distinction.

The other male student who got Distinction is from Dental School (PPSG).

Prof Faridah

Sunday 8 May 2011

Correct message in Islam for Mother's Day

This mp3 will tell you the correct message in Islam for Mother's Day. Please listen to it. Dr Mohamed Tahir brought the message (mp3 below) to my notice. Please thank him.

http://dawahacademy.com/MSM/DawahAcademy.com_Suliman_Mulla-Beloved_Mother.mp3

Prof Faridah

Professional I Exam 10 May 2011 (Part 5)

Dear Medic 1 Students,

Those of you who will be sitting for Distinction Viva, please read up on recent developments in Medicine, especially on Biochemistry. Please take note that viva will cover beyond what was taught in the lecture hall. You really have to read up, know and understand and be able to tell the Viva Panel what you really know to pass and get a distinction. There's no point in giving a distinction to mediocre students. So, if you think you stand a chance at Distinction Viva, then read up. Come prepared to answer our questions. We will challenge you and you can judge whether you will get a distinction or not.

What areas to read up on? Well, look at what's current in Biochemistry. These will include (but not necessarily related to the viva per se though) glucose metabolism and factors that control/regulate blood glucose levels; the central role of hormones in glucose metabolism and how that can tip the balance towards hyperglycaemia; what underlying mechanisms are responsible for hyperglycaemia; hyperglycaemia & hyperlipidaemia co-exist in most chronic diseases wrt diabetes and CVD; what happens to proteins in prolonged hyperglycaemia; what happens to lipoproteins in prolonged hyperlipidaemia as that prevails in diabetes; what are some abnormal products of metabolism in the hyperglycaemic state as occurs in long standing diabetes; what is the commonality (common basis or common element) underlying chronic diseases; what are the hazardous effects of in vivo oxidation that does not lead to ATP production; what are the roles of the antioxidant systems in our bodies; why are peroxides dangerous to our health; what are the body's defense mechanism against oxidative stress: how does the body defend itself against rampant and rapid hazardous oxidation; what are the mechanisms that are protective against reactive oxygen species (ROS); what are the harmful effect of ROS on DNA structure and function; how does the body protect its DNA against damage; if we cannot protect our DNA for lack of some repair systems, what will happen; what happens in the case where repair is sufficient; what happens in the case where repair is insufficient and cannot cope; what are the biochemical mechanisms in cancers we see today; can cancers be stopped and cured; if yes, why; if no, why.

I think I have guided you sufficiently to be able to read up on your own. These areas I think are quite important and relevant to medicine (not only for viva) so you should read, read for knowledge, not just to pass your viva. Remember viva is about test of comprehension, not just what you know. Even if you know a lot, it doesn't mean you can easily pass because we will test your understanding (comprehension) which means you will need to assimilate and understand what you know.

Good luck to those you will be taking the Distinction Viva. May you have a good time at the viva. Remember, if you read widely, you will be able to answer meaningfully. Don't try to memorise without understanding. You will be dead in 5 minutes and won't last 20 minutes.

Take care!

Prof Faridah

Monday 2 May 2011

Structural Organisation of Proteins

Professional I Exam 2 May 2011 (Part 4)

Biochemistry: Structural organisation of proteins


Describe the structural organisation of proteins. (10 minutes)

Guide to answering the above question:
  1. Paraphrase the question: How is protein structure organised? What are the primary, secondary, tertiary and quaternary structure of proteins? Describe the primary, secondary, tertiary and quaternary structure of proteins.
  2. Outline: It is convenient to discuss protein structure in terms of four levels of increasing complexity (from primary to quaternary).
  3. Organise your answer: Answer primary structure first, then secondary structure, followed by tertiary structure and finally quaternary structure. Then give one or two examples of proteins and mention what structural levels they possess. The most common protein used for to answer this question is hemoglobin. You can use other proteins if you have studied their detailed structures,
  4. Website: protein-structures-primary-secondary-tertiary-quaternary/

PROTEINS

PRIMARY STRUCTURE
Primary structure is the sequence of amino acid residues making up the protein. Thus primary structure involves only the covalent bonds linking the amino acid residues together.



The minimum size of a protein is defined as about 50 residues; smaller chains are referred to simply as peptides. So the primary structure of a small protein would consist of a sequence of 50 or so residues. Even such small proteins contain hundreds of atoms and have molecular weights of over 5000 Daltons (Da). There is no theoretical maximum size, but the largest protein so far discovered has about 30,000 residues. Since the average molecular weight of a residue is about 110 Da, that single chain has a molecular weight of over 3 million Daltons.

SECONDARY STRUCTURE
This level of structure describes the local folding pattern of the polypeptide backbone and is stabilized by hydrogen bonds between N-H and C=O groups. Various types of secondary structure have been discovered, but by far the most common are the orderly repeating forms known as the alpha-helix and the beta-pleated sheet.

Alpha-helix
An alpha-helix is a helical arrangement of a single polypeptide chain, like a coiled spring. In this conformation, the carbonyl and N-H groups are oriented parallel to the axis. Each carbonyl is linked by a hydrogen bond to the N-H of a residue located 4 residues further on in the sequence within the same chain. All C=O and N-H groups are involved in hydrogen bonds, making a fairly rigid cylinder. The alpha-helix has precise dimensions: 3.6 residues per turn, 0.54 nm per turn. The side chains project outward and contact any solvent, producing a structure something like a bottle brush or a round hair brush. An example of a protein with many alpha-helical structures is the keratin that makes up human hair.

α-helix: springy/ flexible


Beta-sheet
The structure of a beta-sheet is very different from the structure of an alpha-helix. In a beta-sheet, the polypeptide chain folds back on itself so that polypeptide strands lie side by side, and are held together by hydrogen bonds, forming a very rigid structure. Again, the polypeptide N-H and C=O groups form hydrogen bonds to stabilize the structure, but unlike the alpha-helix, these bonds are formed between neighbouring polypeptide (b) strands. Generally the primary structure folds back on itself in either a parallel or antiparallel arrangement, producing a parallel or antiparallel beta-sheet. In this arrangement, side chains project alternately upward and downward from the sheet. The major constituent of silk (silk fibroin) consists mainly of layers of beta-sheet stacked on top of each another.
  
β-sheet:
  • Hydrogen bonding
  • (e.g silk)
  • High tensile strength due to hydrogen bonding



Other
There are other types of secondary structure. While the alpha-helix and beta-sheet are by far the most common types of structure, many others are possible. These include various loops, helices and irregular conformations. A single polypeptide chain may have different regions that take on different secondary structures. In fact, many proteins have a mixture of alpha-helices, beta-sheets, and other types of folding patterns to form various overall shapes.

Interactions
What determines whether a particular part of a sequence will fold into one or the other of these structures? A major determinant is the interactions between side chains of the residues in the polypeptide. Several factors come into play: steric hindrance between nearby large side chains, charge repulsion between nearby similarly-charged side chains, and the presence of proline. Proline contains a ring that constrains bond angles so that it will not fit exactly into an a helix or b sheet. Further, there is no H on one peptide bond when proline is present, so a hydrogen bond cannot form. Another major factor is the presence of other chemical groups that interact with each other. This contributes to the next level of protein structure, the tertiary structure.
 
TERTIARY STRUCTURE
This level of structure describes how regions of secondary structure fold together – that is, the 3D arrangement of a polypeptide chain, including alpha-helices, beta-sheets, and any other loops and folds. Tertiary structure results from interactions between side chains, or between side chains and the polypeptide backbone, which are often distant in sequence. Every protein has a particular pattern of folding and these can be quite complex.

Stabilisation of protein structure
Whereas secondary structure is stabilized by H-bonding, all four “weak” forces contribute to tertiary structure. Usually, the most important force is hydrophobic interaction (or hydrophobic bonds). Polypeptide chains generally contain both hydrophobic and hydrophilic residues. Much like detergent micelles, proteins are most stable when their hydrophobic parts are buried, while hydrophilic parts are on the surface, exposed to water. Thus, more hydrophobic residues such as trp are often surrounded by other parts of the protein, excluding water, while charged residues such as asp are more often on the surface.


Other forces that contribute to tertiary structure are ionic bonds between side chains, hydrogen bonds, and van der Waals forces. These bonds are far weaker than covalent bonds, and it takes multiple interactions to stabilize a structure.

There is one covalent bond that is also involved in tertiary structure, and that is the disulfide bond that can form between cysteine residues. This bond is important only in non-cytoplasmic proteins since there are enzyme systems present in the cytoplasm to remove disulfide bonds.

Visualization of protein structures 
Because the 3D structures of proteins involve thousands of atoms in complex arrangements, various ways of depicting them so they are understood visually have been developed, each emphasizing a different property of the protein. Software tools have been written to depict proteins in many different ways, and have become essential to understanding protein structure and function.

Structural Domains of Proteins
Protein structure can also be described by a level of organization that is distinct from the ones we have just discussed. This organizational unit is the protein “domain,” and the concept of domains is extremely important for understanding tertiary structure. A domain is a distinct region (sequence of amino acids) of a protein, while a structural domain is an independently-folded part of a protein that folds into a stable structure. A protein may have many domains, or consist only of a single domain. Larger proteins generally consist of connected structural domains. Domains are often separated by a loosely folded region and may create clefts between them.

Tertiary Structure
  • further folding and super coiling of the polypeptide
  • controlled by interactions (covalent, ionic, van der Waals) between the R-groups or side chains of the amino acids

Interacts with watery environment of the cytoplasm to drive folding process.
  • Gives protein a specific 3-dimensional shape and a specific function.  What would happen to the protein if these bonds were broken? Denaturation

QUATERNARY STRUCTURE
Some proteins are composed of more than one polypeptide chain. In such proteins, quaternary structure refers to the number and arrangement of the individual polypeptide chains. Each polypeptide is referred to as a subunit of the protein. The same forces and bonds that create tertiary structure also hold subunits together in a stable complex to form the complete protein.

Quaternary Structure
  • Two or more polypeptides interacting to form a functional protein
  • Metal ions may be part of the protein structure as in



Individual chains may be identical, somewhat similar, or totally different. As examples, CAP protein is a dimer with two identical subunits, whereas hemoglobin is a tetramer containing two pairs of non-identical (but similar) subunits. It has 2 alpha subunits and 2 beta subunits.

Structure of hemoglobin

Hemoglobin with Fe2+
  • Allows for very specific activity of the protein due to detailed globular shape and
    • collagen triple helix
  • Indivisible, tensile (strong), flexible
  • Responsible for skin elasticity
  • 4 heme groups allows it to bind 4 oxygen molecules
  • Successive oxygen binding is accelerated
  • 1st oxygen is hardest to bind

Allosteric Co-operativity
  • Property of quaternary structure
  • Activates activity of a protein through its initial bonding
Secreted proteins often have subunits that are held together by disulfide bonds. Examples include tetrameric antibody molecules that commonly have two larger subunits and two smaller subunits (“heavy chains” and “light chains”) connected by disulfide bonds and noncovalent forces.

In some proteins, intertwined alpha-helices hold subunits together; these are called coiled-coils. This structure is stabilized by a hydrophobic surface on each alpha-helix that is created by a heptameric repeat pattern of hydrophilic/hydrophobic residues. The sequence of the protein can be represented as “abcdefgabcdefgabcdefg…” with positions “a” and “d” filled with hydrophobic residues such as A, V, L etc. Each a helix has a hydrophobic surface that therefore matches the other. When the two helices coil around each other, those surfaces come together, burying the hydrophobic side chains and forming a stable structure. An example of such a protein is myosin, the motor protein found in muscle that allows contraction.

Protein Folding
How and why do proteins naturally form secondary, tertiary and quaternary structures? This question is a very active area of research and is certainly not completely understood. A folded, biologically-active protein is considered to be in its “native” state, which is generally thought to be the conformation with least free energy.

Proteins can be unfolded or “denatured” by treatment with solvents that disrupt weak bonds. Thus organic solvents that disrupt hydrophobic interactions, high concentrations of urea or guanidine that interfere with H-bonding, extreme pH or even high temperatures, will all cause proteins to unfold. Denatured proteins have a random, flexible conformation and usually lack biological activity. Because of exposed hydrophobic groups, they often aggregate and precipitate. This is what happens when you fry an egg.

If the denaturing condition is removed, some proteins will re-fold and regain activity. This process is called “renaturation.” Therefore, all the information necessary for folding is present in the primary structure (sequence) of the protein. During renaturation, the polypeptide chain is thought to fold up into a loose globule by hydrophobic effects, after which small regions of secondary structure form into especially favorable sequences. These sequences then interact with each other to stabilize intermediate structures before the final conformation is attained.

Many proteins have great difficulty renaturing, and proteins that assist other proteins to fold are called “molecular chaperones.” They are thought to act by reversibly masking exposed hydrophobic regions to prevent aggregation during the multi-step folding process. Proteins that must cross membranes (eg. mitochondrial proteins) must stay unfolded until they reach their destination, and molecular chaperones may protect and assist during this process.

Protein families/Types of proteins
Proteins are classified in a number of ways, according to structure, function, location and/or properties. For example, many proteins combine tightly with other substances such as carbohydrates (“glycoproteins”), lipids (“lipoproteins”), or metal ions (“metalloproteins”). The diversity of proteins that form from the 20 amino acids is greatly increased by associations such as these. Proteins that are tightly bound to membranes are called “membrane proteins”. Proteins with similar activities are given functional classifications. For example, proteins that break down other proteins are called proteases.
Because almost all proteins arise by an evolutionary process, ie. new ones are derived from old ones, they can be classified into families by their relatedness. Proteins that derive from the same ancestor are called “homologous proteins”. Studying the sequences of homologous proteins can give clues to the structure and function of the protein. Residues that are critical for function do not change on an evolutionary timescale; they are referred to as “conserved residues”.  Identifying such residues by comparing amino acid sequences often helps clarify what a protein is doing or how it is folded. For example the proteases trypsin and chymotrypsin are members of the “serine protease” family; so-named because of a conserved serine residue that is essential to catalyze the reaction. Trypsin and chymotrypsin contain very similar folding patterns and reaction mechanisms. Recognizing a pattern of conserved residues in protein sequences often allows scientists to deduce the function of a protein.

Relevant diagram:


PowerPoints



Professional I Exam 2 May 2011 (Part 3)

Biochemistry: Oxidative phosphorylation

Describe oxidative phosphorylation (10 minutes).

Guide to answering this question:
  1. Which compartment? Mitochondria
  2. What is it about? It involves the production of ATP in the mitochondria under aerobic conditions, with the simultaneous formation of water from oxygen and hydrogen. 
  3. What are the necessary conditions? Aerobic
  4. How does it happen/What are the reactions? Coupled reactions for the formation of ATP & water
  5. What are the sources/feeders? For the hydrogens, it involves electrons passed down the electron transport chain (ETC) by reducing equivalents (NADH & FADH2) which enter the ETC to give their electrons.
  6. What are the products? ATP and water
  7. What is the purpose of this? Oxidative phosphorylation is the final stage of complete biological oxidation for the production of ATP. Water is the waste product, also cools down all the heat that comes from electrons passing through ETC.
Some relevant diagrams:








Professional I Exam 2 May 2011 (Part 2)

Dear Medic Year 1 Students,

Re: SEQ1

You had 9 essay questions @10 minutes each.
Here are the questions (if I remember them correctly; no particular order):
  1. Bioethics & Social Science: Empathy vs Sympathy
  2. Haematology: Haemostasis
  3. Haematology: Transport of oxygen in blood from lungs to tissue
  4. Anatomy: CNS - Brain & spinal cord - meninges
  5. Anatomy: Lungs?
  6. Physiology: Sound travel and hearing mechanism
  7. Physiology: CVS question?
  8. Biochemistry: Oxidative phosphorylation
  9. Biochemistry: Stuctural organisation of proteins

I noticed that some of you drew quite elaborate diagrams for Anatomy & Biochemistry questions. Some had ugly handwriting. Some wrote quite haphazard too - wrote all over the place. There were some who could not answer Biochemistry Oxidative Phosphorylation. Many students could not finish answering all the exam questions.

I was talking to two of the lecturers who were invigilating with me this morning. We think the questions were standard and appropriate for Professional I. I was told that some questions were from Form 5.

Prof Faridah

Professional I Exam 2 May 2011 (Part 1)

Dear Medic Year 1 Students,
I hope you have recovered from today's exam paper (SEQ1). I invigilated this morning and took some photos of you but not everyone. I will try to answer the question on biochemistry in another post(s). There were about 5 students who brought their handphones into the exam hall - you cannot do that in future - leave them outside in your bags. One girl did not have her MyKad and Matric card with her in the exam hall - you must have the 2 IDs with you throughout the exam period. Just don't repeat your mistakes in future exams.
Prof Faridah

Here are your photos from this morning. Download and keep them, show them to your parents & siblings.

Exam venue - Dewan Utama, USM Health Campus
Baru sampai
Last minute studying
Girls are more relaxed
In the foyer
PPSP on the left side of the hall
PPSP on the left, PPSK on the right
Medic students fill in PPSP side
Medic students finding their assigned tables in the exam hall.
Checking the board for assigned tables
Leave your handphones in your bags outside the hall. Just bring in your MyKad & Matric card.
All seated and listening to instructions from the Chief Invigilator.
Put your MyKad & Matric card on the right side of your table so the invigilators can see them clearly. Fill in the exam attendance slip (small green piece of paper). Listen to more instructions from the Chief Invigilator. Check the contents of question envelope labeled 'A' - altogether 9 essay questions and all pages are printed. Put your hand up if you have problems. Professional I begins 9 am - 10:30am. No extra time is given.
Invigilators' table
Counting the collected exam scripts
Students exit the exam hall
Students outside the exam hall, some walking back to the hostels
Done for the day...
Most students returned to the hostels to have breakfast/brunch/early lunch.