BIOL1040 Modules1&3 CellBiol Biochem Lectorial Sem1 2012 (NEED to PRINT)

© A/Prof Lesley Lluka

BIOL1040MODULES 1 & 2:

BIOL1040MODULES 1 & 2:

CELL BIOLOGY & BIOCHEMISTRYLectorial

Assoc Profs Luke Guddat & Lesley LlukaSchool of Chemistry & Molecular BiosciencesSchool of Chemistry & Molecular Biosciences

& School of Biomedical Sciencesh U i i f Q l dThe University of Queensland

[email protected] [email protected]


Let’s introduce JackHe is a 13 year old boyLet s introduce Jack…….

for some weeks now he has been losing weightg g

this is despite being particularly hungry which hisparticularly hungry which his mother assumes is just because of his agebecause of his age

he has also been very thirsty and has been urinating moreand has been urinating more frequently than usual

Wh t d thi k hi GPWhat do you think his GP would be testing for?11


Jack and his mother go to see their GPJack and his mother go to see their GP….. The doctor told Jack’s mother that The doctor told Jack s mother that Jack must not eat overnight before coming for the appointment with him

His fasting venous plasma glucose His fasting venous plasma glucose level gave a value of 8 mmol/l –normal is about 5 mmol/l

Let’s consider what we know about glucose, insulin and relevantglucose, insulin and relevant concepts before we think about a diagnosis and treatment for Jack....

12


Which of the following statements is CORRECT regarding transport across cell membranes? Both facilitated diffusion and active transport

A. use proteins to mediate transport across the cell membrane

B. can be mediated by ion channels

C. can generate electrical potentials across cells

D. require the solute to dissolve in th h h li id bilthe phospholipid bilayer

E. require energy from ATP

0% 0% 0%0%0% 1010A. B. C. D. E.

10100 of 500


Glucose transport across intestinal and renal epithelial cells occurs via a Na+‐glucose co‐transporter. Glucose transport across other cell membranes uses different transporters that are independent of Na+. Which of the following statements is CORRECT regarding glucoseWhich of the following statements is CORRECT regarding glucose transport across cell membranes?

A Glucose is water soluble and hence readily diffuses acrossA. Glucose is water soluble, and hence readily diffuses across cell membranes

B. Glucose is accumulated against its concentration gradient g gby glucose transporters in all cell types

C. Energy from ATP is required for the transport of glucose to i ll i h N + i d d loccur in cells with Na+‐independent glucose transporters

D. Na+/K+‐ATPase can indirectly drive active glucose transport across renal epithelial cell membranes

1010

across renal epithelial cell membranes

E. Na+ ions and glucose only move along their concentration gradients during co‐transport in intestinal cell membranes

A. B. C. D. E.

0% 0% 0%0%0%1010

0 of 500

Cotransport: active transport driven by a concentration gradient

ATP

Na+Na+Na+

Na+/K+‐ATPase

Na+

Na+-glucose cotransporter

Diffusionof Na+

Na

Glucose–GlucoseGlucose


There are several possibilities related to the structure of Jack’s insulin that could account for his present illness. In the back of his mind, Jack’s doctor recalls some basic knowledge of insulin from his studies at UQ Which concept is WRONG?his studies at UQ. Which concept is WRONG?

A. Insulin is expressed by the ribosome as i l l tid h ia single polypeptide chain

B. Insulin becomes active only upon l i lproteolytic cleavage

C. The active form of insulin is stabilized b i h i di lfid b dby an intrachain disulfide bond

D. The active form of insulin is stabilized

0% 0% 0%0%0% 1010

by interchain disulfide bonds

E. Proinsulin is the fully folded and most

A. B. C. D. E.0 of 500

1010active form of insulin

His doctor considers the possibility that Jack has inherited the disease. He searches the web and finds that a leucine to valine mutation in insulin can lead to onset of diabetes.

Valine Leucine Aspartatep

V

pKa of carboxylate proton is 4Side‐chains are highlighted in pink


His doctor considers the possibility that Jack has inherited the disease. He searches the web and finds that a leucine to valine mutation in insulin can lead to onset of diabetes. Which of h ld NOT b i h d ’ ?these would NOT be correct in the doctor’s assessment?

A. Such a change would be described as a conservative substitution in gthe polypeptide sequence

B. A change at the DNA level must have resulted in the change from leucine to valine

C. The side chains of leucine and valine have the ability to form covalent bonds between each other thereby inactivating insulinbonds between each other, thereby inactivating insulin

D. Leucine is likely to be buried in the interior of insulin, a globular protein. Hence, this change may only mildly affect insulin function

1010

p g y y y

E. A change from leucine to aspartate at this site would be more likely to result in insulin not maintaining its folded 3‐dimensional structure

A. B. C. D. E.

0% 0% 0%0%0% 10100 of 500


So Jack has Type 1 diabetes mellitusSo Jack has Type 1 diabetes mellitusWhy is his blood glucose level high?

How can we get Jack’s blood glucose level under control?control?

Why is he excreting excessive amounts of urine containing glucose?

19


Introduction to next 2 questionsIntroduction to next 2 questions....

In a normal subject.....j

After eating a meal, increases in blood glucose stimulate l f i li f b t ll i threlease of insulin from beta cells in the pancreas.

Insulin acts on tyrosine kinase linked receptors to l f th bl dremove glucose from the blood.

Jack’s beta cells are not secreting insulin.

When blood glucose levels decrease below a set point, glucagon is secreted by alpha cells in the pancreas. Glucagon acts on G‐protein coupled receptors to

increase blood glucose levels.

20

Jack’s alpha cells are functioning normally.


Which of the following statements is INCORRECT d h f l d l ?regarding the receptors for insulin and glucagon?

A. Glucagon receptors, but not insulin receptors, have 7 transmembrane domains

B I li d l t h thB. Insulin and glucagon receptors have the same fast activation speed of msec

C Insulin receptors but not glucagonC. Insulin receptors, but not glucagon receptors, activate protein phosphorylation by kinasesp p y y

D. Insulin and glucagon receptors are from different receptor families

0% 0% 0%0%0%

E. Stimulation of glucagon receptors activates a heterotrimeric G‐protein 1010

A. B. C. D. E.0 of 500

1010


InsulinInsulin

A. receptors are present only on beta cells p p yin the pancreas

B. inactivates receptor‐mediated phosphorylation cascades in cells

C. interacts with an intracellular steroid receptor in liver cells

D. is a hormone that travels from the di ll i hpancreas to distant cells via the

circulation

E activates ion channel linked receptors

0% 0% 0%0%0% 1010

E. activates ion channel linked receptors in neurons

A. B. C. D. E.0 of 500

1010


Short answer questionq

Before his insulin therapy, Jack has a highBefore his insulin therapy, Jack has a high output of urine which contains glucose.

Given that his high blood glucose concentration results in excretion of excess glucose by the g ykidneys, rationalize Jack’s high urine output.

Hint: You need to apply your knowledge of osmosis to this question.

24


Short answer question – model answeranswerQUESTION: Before his insulin therapy, Jack has a high

f h h loutput of urine which contains glucose.Given that his high blood glucose concentration

results in excretion of excess glucose by the kidneys, rationalize Jack’s high urine output.

ANSWER: Glucose in kidney tubules exceeds reabsorptive capacity↓↓

Excess glucose in the filtrate exerts osmotic pressure since it is not reabsorbed

↓An osmotic equivalent of water is taken into the tubules

↓

25

↓Causes excretion of increased volume of urine containing glucose


After a few weeks, including a short stay in hospital, Jack is stabilized on daily insulin injections with topup doses at meal times.

26


After a few weeks, including a short stay in hospital, Jack is stabilized on daily insulin injections with topup doses at meal times. Which statement is INCORRECT?

A. Insulin increases the activity of transporters for glucose uptake into body cells

B. Insulin reduces the concentration of glucose in Jack’s blood

C. Insulin stimulates the breakdown of glycogen to glucose in muscle

i h h l i di hD. Protein phosphorylation mediates the actions of insulin in cells

E I li t it t ith t b i

0% 0% 0%0%0%

E. Insulin acts on its receptors without being transported into the cells

1010A. B. C. D. E.

10100 of 500


Jack decided to call in to Fasta Pasta for a meal. After eating he hops on his bike to ride home.

As a result of his visits to the doctor and to hospital, he d t d th t th f d h t t i thunderstands that the food he eats contains the

chemicals he needs to power his bike ride.

Which of these chemical processes will allow him to arrive home?arrive home?

28


Which of these chemical processes will allow him to arrive home?A. Glucose being converted to carbon

dioxide by a single chemical reaction

B. The enzymes that break glucose down to k b hpyruvate work by increasing the

activation energy barrier in converting substrates to productssubstrates to products

C. Export of pyruvate from the mitochondria to produce NAD+mitochondria to produce NAD

D. Oxidative phosphorylation leading to production of a large number of ATP

0% 0% 0%0%0% 1010

p gmolecules

E. Electrons being fed into ATP synthase to

A. B. C. D. E.

10100 of 500

produce ATP


About halfway home he notices a scrunched up piece of paper on the roadside.paper on the roadside.

Being a member of Ian Kiernan’s clean up Australia g pteam he stops to pick up the paper.

He reads the first line ‘First draft of MCQs for BIOL1040 exam 2012’.......

30


It continues..... “Q1. A strong covalent bond that is between amino acids and functions in maintaining a polypeptide's specific three‐dimensional shape is a (an)

A. ionic bond

B d W l i iB. van der Waals interaction

C. disulfide bond

D. hydrophobic interaction

E. hydrogen bondE. hydrogen bond

0% 0% 0%0%0% 1010A. B. C. D. E.

10100 of 500


“Q2. Which of the following statements regarding nucleotides is NOT correct? A. Nucleotide monomers are linked together to

build a polynucleotidebuild a polynucleotide

B. Adjacent nucleotides are joined by covalent bonds that form between the –OH group on g pthe 3’ carbon of one nucleotide, and the phosphate on the 5’ carbon on the next

C. Nucleotide polymers have a backbone of sugar‐phosphate units, with nitrogenous bases as appendagesappendages

D. The sequence of bases along a DNA or mRNA polymer is unique for each gene

0% 0% 0%0%0% 1010E. In the DNA double helix, the nitrogenous bases

pair up and form H‐bonds, so that A always pairs with G and T always pairs with C

A. B. C. D. E.

10100 of 500

pairs with G, and T always pairs with C


“Q3 Wh t i t i l l l?“Q3. What is a triacylglycerol?

A a molecule formed from threeA. a molecule formed from three alcohols by dehydration reactions

b h h hB. a carbohydrate with three sugars joined together by glycosidic linkages

C. a lipid made with three fatty acids and glycerol

D. a protein with tertiary structure

E a lipid that makes up much of the

0% 0% 0%0%0% 1010

E. a lipid that makes up much of the plasma membrane

A. B. C. D. E.

0% 0% 0%0%0% 10100 of 500


Back at school, Jack notices that one of his classmates, Max, who recently arrived from Africa, is absent.Max, who recently arrived from Africa, is absent.

Actually, Max is often absent from school after sports y, pevents.

His teacher explains that he is in hospital and has been diagnosed with the disease sickle cell anemia.

34


h h f h f ll l k l bWhich of the following is most likely to be correct in relation to Max and the disease sickle cell anemia?

A. His haemoglobin binds too much oxygen

B Hi h l bi f d bl h liB. His haemoglobin forms a double helix

C. He has not been taking enough vitamin C

D. His DNA that encodes for haemoglobin has an unusual base compared to the

t f th t d t i th lrest of the students in the class

E. His form of haemoglobin makes him hi hl ibl l i l di

0% 0% 0%0%0% 1010

highly susceptible to malaria leading to sickle cell anemia

A. B. C. D. E.

0% 0% 0%0%0% 10100 of 500


Back home at Jack’s placeBack home at Jack s place....

To celebrate Jack’s diagnosis and successful stabilizationTo celebrate Jack s diagnosis and successful stabilization on his insulin regime, his parents took him out for dinner at the local hotel.

His dad had a few beers but thought it OK to drive home. Unfortunately, this happened. Why?

36


Wh did h id h ?Why did the accident happen?

A. Ethanol and water don’t mix

B. Ethanol has an hydroxyl y yfunctional group

C. Ethanol forms hydrophobic y pbonds with water

D. Ethanol is highly ionict a o s g y o c

E. Jack’s mother was navigating

0% 0% 0%0%0% 1010A. B. C. D. E.

10100 of 500


And more on why the accident happened. Which of the following statements is CORRECT?A. It only occurred because Jack’s

father normally does not drink any alcohol

B. Jack’s father became unconscious while driving because he also has diabetes

C. Ethanol stimulates insulin receptors

D. A specific transporter actively transports ethanol into the brain

0% 0% 0%0%0% 1010E. Ethanol is small enough to diffuse

across cell membranes into the brain

A. B. C. D. E.

10100 of 500


d f llAnd finally....

The car was a write off but fortunately injuries to JackThe car was a write‐off, but fortunately injuries to Jack and his parents were limited to minor lacerations.

Jack’s father will definitely be handing the wheel over to his wife next time he has a few drinks when they gohis wife next time he has a few drinks when they go out....

And Jack is getting used to managing his diabetes as part of his daily routine – for life!

39

y


COMMONWEALTH OF AUSTRALIA

Copyright Regulations 1969

WARNING

This material has been reproduced and communicated to you by or on behalf of the University of Queensland pursuant to Part VB of the Copyright Act 1968 (the Act).

The material in this communication may be subject to i h d h A A f h d icopyright under the Act. Any further reproduction or

communication of this material by you may be the subject of copyright protection under the Actsubject of copyright protection under the Act.

Do not remove this notice.

40

BIOL1040 Modules1&3 CellBiol Biochem Lectorial Sem1 2012 (NEED to PRINT)

Documents

Transcript of BIOL1040 Modules1&3 CellBiol Biochem Lectorial Sem1 2012 (NEED to PRINT)