Introduction Biochem Fall 2014

8/11/2019 Introduction Biochem Fall 2014

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INTRODUCTION TOBIOCHEMISTRY

This lecture course will cover:

amino acids (2), proteins (4), enzymes (1),

nucleotides (1), lipids (5), carbohydrates (3),

TCA cycle + ETC (2), oxygen (1), DNA/RNA (9),

immune system (2), GIT (2), liver (2),

receptors (1), hormones (6), alcohol (1), toxins (1),

nutrition (5).



But why study Biochemistry?

What do you need it for?

What is the relevance to clinical practice?



The global trend is towards evidence based

medicine.

This requires the ability to understand the reason

why a disease or condition exhibits the profile of

signs and symptoms that it does, not just whatpattern to recognise.

Modern clinicians need to be able to explain and

justify their diagnoses, not just cite previous

examples.

In other words, understand not just know.



To be able to do this requires a knowledge and

comprehension of the basic science underlyingclinical practice.

And this requires a knowledge of Anatomy

(human structure), and Physiology and

Biochemistry (human function).



The problem with pattern recognition in medicine

is that it tends to lump similar conditionstogether - ones that show similar signs and

symptoms - but that may have very different

causes and so require different treatments.

For example, diabetes mellitus occurs in 2

different forms, type 1 and type 2. Both show

similar patterns of derangement of plasma

composition, but for different underlying causes.



NORMAL TYPE I TYPE II FASTINGPLASMA

INSULIN 40 <5 20 <5GLUCAGON 80 300 140 140GLUCOSE 5.5 >30 8.5 3.5FATTY ACIDS 0.4 1.7 1.7 1.7KETONES <0.1 >20 9.0 6.0LACTATE 1.0 0.7 0.7 0.6pH 7.40 7.05 7.35 7.25

From the above you can see it's not just a

problem of too little insulin/function, but this isalso compounded by an increase in glucagon as a

result of the 'stress' situation.



An understanding of the Physiology and

Biochemistry of diabetes allows for better

assessment of the patient, better differential

diagnosis and better treatment of the condition.

Merely knowing that their plasma glucose isincreased does not characterise the type of

diabetes.

Understanding the disease and the differences

between the two types, and thus what to test

for, does.



Another example is Cushings.

The syndrome is characterised by redistributionof body fat, severe muscle and connective

tissue wasting, osteoporosis, hypertension and

diabetes.

The disease may also show patchy

hyperpigmentation since adrenocorticotrophin

(ACTH) is structurally very similar to

melanocyte stimulating hormone (MSH).

There are 2 possible major causes.



The signs/symptoms of both are the same -

protuberant abdomen (central obesity); thin

arms and legs; acne or skin infections; collection

of fat on the back of the neck (buffalo hump);

depression; diabetes; easy bruising; excessive

facial hair growth in females (hirsutism);

headache; impotence; increased urination

(polyuria); moon face (round, red, and full);

osteoporosis; purple stretch marks on the

abdomen, thighs, and breasts; cessation of

menstruation (amenorrhea); weakness; mass gain.



The classic Cushings disease is a result of a

tumor in the pituitary gland, causing excess

adrenocorticotrophin (ACTH) release. This then

causes increased cortisol release by the adrenal

cortex, with all the signs and symptoms typical

of too much cortisol on a prolonged basis.

The other form, Cushings syndrome, is not a

problem with the pituitary, but rather a tumorin the adrenal cortex itself, but this again

causes excess cortisol release and again on a

prolonged basis.



The key diagnostic difference is that in

Cushings disease ACTH is increased, while inthe syndrome it is decreased because of

negative feedback of cortisol on ACTH release

by the anterior pituitary.

Without an understanding of the possibility of

the 2 types, and what profile of plasma

components to expect, it would be very difficult

to differentiate between them and hence how

to treat them.



OK, having given you an idea of why we need

Physiology and Biochemistry. What will the

course structure look like?

While there is a reference textbook (Lehninger)

the lectures are a synthesis from several other

sources as well and do not slavishly follow a

chapter sequence.

The textbook should be used to clarify any

uncertainty, rather than as the base source,

that should be the lecture content.



The key concepts that need to be understood are:

• All those related to energy metabolism -

glycogenesis/glycogenolysis, lipolysis/lipogenesis,glycolysis/gluconeogenesis, pentose phosphate

pathway, 2,3-BPG, TCA cycle, ETC, β-oxidation;

• Interconversion of amino acids, protein turnover,nucleotide turnover;

• Essential nutrients;

• Control of the pathways;

• Different pathways in different tissues;

• Integration of all the above - that's Biochemistry.



The major pathways of energy metabolism are:glycolysis, gluconeogenesis, lipolysis, lipogenesis,glycogenolysis, glycogenesis, β-oxidation,tricarboxylic acid cycle, and electron transportchain.

Within these glycolysis, lipolysis, glycogenolysis, β-oxidation, tricarboxylic acid cycle, and electrontransport chain are all catabolic to produce ATP

(energy).

While gluconeogenesis, lipogenesis and glycogenesisare all anabolic to produce energy-rich fuel molecules

for storage.

ENERGY METABOLISM

AN OVERVIEW



Fairly obviously, catabolic pathways are alwaysworking as the body always needs a certain degree

of energy supply.

Between meals, when there is no energy intake, thecatabolic pathways predominate.

After meals, the anabolic pathways predominate tostore the incoming energy-rich molecules.

But none of them ever totally shut down, just oneform or the other is most active.

And the degree of activity varies between differenttissues and organs.



BASIC ROUTE MAP OF THE PATHWAYS - RBC

GLUCOSE-6-P

PYRUVATELACTATE

GLUCOSE

Glycolysis

PLASMA

CYTOSOL

AMINO

ACIDS

AMINO

ACIDS

Transamination

ATP/ADP



BASIC ROUTE MAP OF THE PATHWAYS - BRAIN

GLUCOSE-6-P

PYRUVATE

ACETYL-CoA

ETC

TCA Cycle

LACTATE

GLUCOSE

ATP/ADP

Glycolysis/Gluconeogenesis

KETONES

MITOCHONDRION

PLASMA

CYTOSOL

ATP/ADP

AMINO

ACIDS

AMINO

ACIDS

Transamination

ATP/ADP



BASIC ROUTE MAP OF THE PATHWAYS - MUSCLE

GLUCOSE-6-P

GLYCOGEN

PYRUVATE

ACYLCoA

ACETYL-CoA

ETC

TCA Cycle

LACTATE

TAG

ATP/ADP

GLUCOSE

FATTY

ACID

Glycolysis/Gluconeogenesis

Glycogenolysis/Glycogenesis

β-oxidation

MITOCHONDRION

PLASMA

CYTOSOL

ATP/ADP

AMINO

ACIDS

AMINO

ACIDS

Transamination

Lipogenesis/Lipolysis

ATP/ADP



Energy production (ATP from ADP) comes from thebreakdown of energy-rich molecules to produceNADH2 and FADH2 from NAD and FAD.

In aerobic metabolism (requiring oxygen) glycolysis,the TCA cycle and β-oxidation produce NADH2 andFADH2. They are recycled back to NAD and FAD via

the ETC, with the production of water and ATP.

Glycolysis (to pyruvate) produces 2 NADH2 and 2ATP. Pyruvate to acetylCoA produces 2 NADH2. β-oxidation produces 1 NADH2, 1 FADH2 and 1

acetylCoA per cycle. The TCA cycle produces 3NADH2, 1 FADH2 and 1 ATP per cycle.

All of these are recycled to NAD and FAD via the

ETC.



In anaerobic metabolism (absence of oxygen) only glycolysis (topyruvate) continues, which only produces 2 NADH2 and 2 ATP.

These are recycled back to NAD via lactate.

Thus the core of energy metabolism is the continual recycling ofNAD and FAD.

METABOLISM IN LIVER - A SIMPLIFIED OUTLINE



23

METABOLISM IN LIVER - A SIMPLIFIED OUTLINEGLYCOGEN

UDP-GLUCOSEPLASMA

GLUCOSE G-1-P

NUCLEOTIDES, VLDLG-6-P NADP NADPH2 RNA/DNA

TAGRIBULOSE-5-P

F-6-P

F-1,6-BP GLYCEROL

GLYCEROL-3-PDHAP GLYCERALDEHYDE-3-P

PEP ACYLCoA

PYRUVATECYTOSOL ACYLCoA

ALANINE LACTATE ACETYLCoA MALONYLCoA

ACETYLACPAMINO ACIDS

ASPARTATEOXALOACETATE CITRATE HMGCoA CHOLESTEROL

PROTEINSNADH2

ISOCITRATE KETONESNAD

MALATE NADCO2 NADH2

α-KETOGLUTARATEFUMARATE

NAD GLUTAMATECO2

FADH2 SUCCINYLCoA NADH2

SUCCINATEFAD GDP

GTPMITOCHONDRION ATP

ADP

ATP ETC



Day Date Topic Faculty

Monday 01 – Sept

Tuesday 02 Orientation DavidsonWednesday 03 Introduction Davidson

Thursday 04 Amino Acids 1 Davidson

Friday 05 Amino Acids 2 Davidson

Sat/Sun 06/07

Monday 08 Proteins 1 Sterling

Tuesday 09 Proteins 2 Sterling

Wednesday 10 Proteins 3 Sterling

Thursday 11 Proteins 4 Sterling

Friday 12 Enzymes Sterling

Sat/Sun 13/14

Monday 15 Purines/Pyrimidines Sterling

Tuesday 16 Lipids - 1 Davidson

Wednesday 17 Lipids - 2 Davidson

Thursday 18 Lipids - 3 Davidson

Friday 19 Lipids - 4 Davidson

Lecture Schedule



Sat/Sun 20/21

Monday 22 Lipids - 5 Davidson

Tuesday 23 Case Studies Davidson

Wednesday 24 Review DavidsonThursday 25 Study Day

Friday 26 Block 1 Exams Davidson/Sterling

Sat/Sun 27/28

Monday 29 Block 1 Exams Davidson/Sterling

Tuesday 30 Carbohydrates 1 Damuni

Wednesday 01 – Oct Carbohydrates 2 DamuniThursday 02 Carbohydrates 3 Damuni

Friday 03 TCA Cycle Damuni

Sat/Sun 04/05

Monday 06 Electron Transport Chain Damuni

Tuesday 07 Oxygen Damuni

Wednesday 08 DNA/RNA 1 Damuni

Thursday 09 DNA/RNA 2 Damuni

Friday 10 Presentations Damuni



Sat/Sun 11/12

Monday 13 DNA/RNA 3 Damuni

Tuesday 14 DNA/RNA 4 Damuni

Wednesday 15 DNA/RNA 5 Damuni

Thursday 16 DNA/RNA 6 Damuni

Friday 17 DNA/RNA 7 Damuni

Sat/Sun 18/19

Monday 20 DNA/RNA 8 Damuni

Tuesday 21DNA/RNA 9

Damuni

Wednesday 22 Presentations Damuni

Thursday 23 Study Day

Friday 24 Block 2 Exams Damuni

Sat/Sun 25/26

Monday 27 Block 2 Exams Damuni

Tuesday 28 Immune System 1 Sterling

Wednesday 29 Immune System 2 Sterling

Thursday 30 Gastro-Intestinal Tract (GIT) 1 Sterling

Friday 31 Gastro-Intestinal Tract (GIT) 2 Sterling



Sat/Sun 01/02 - Nov

Monday 03 Liver 1 Sterling

Tuesday 04 Liver 2 Sterling

Wednesday 05 Presentations Sterling

Thursday 06 Hormone Receptors Damuni

Friday 07 Endocrines 1 Damuni

Sat/Sun 08/09

Monday 10 Endocrines 2 Damuni

Tuesday 11 Endocrines 3 DamuniWednesday 12 Endocrines 4 Damuni

Thursday 13 Endocrines 5 Damuni

Friday 14 Endocrines 6 Damuni

Sat/Sun 15/16

Monday 17 Presentations Damuni

Tuesday 18 Presentations Damuni

Wednesday 19 Review Damuni

Thursday 20 Study Day

Friday 21 Block 3 Exams Damuni/Sterling



Sat/Sun 22/23

Monday 24 Block 3 Exams Damuni/Sterling

Tuesday 25 Alcohol Davidson

Wednesday 26 Toxins Davidson

Thursday 27 Nutrition - 1 Davidson

Friday 28 Nutrition - 2 Davidson

Sat/Sun 29/30

Monday 01 – Dec Nutrition - 3 Davidson

Tuesday 02 Nutrition - 4 DavidsonWednesday 03 Nutrition - 5 Davidson

Thursday 04 Case Studies Davidson

Friday 05 Review Davidson

Sat/Sun 06/07

Monday 08 Presentations Davidson

Tuesday 09 Presentations Davidson

Wednesday 10 Presentations Davidson

Thursday 11 Presentations Davidson

Friday 12 Study Day



Sat/Sun 13/14

Monday 15 Study Day

Tuesday 16 Block IV Exam Davidson

Wednesday 17 Study Day

Thursday 18 Block IV Exam Davidson

Friday 19 Public Holiday

Sat/Sun 20/21

The course will be taught by three experts:Dr Zahi DamuniDr Ken Sterling

Dr Bruce Davidson



Intended Learning Objectives

At the end of this course, each student should be able to

demonstrate:

Knowledge and understanding of the normal structure, function

and development of the human body, organ systems and mind at

all stages of life, with special emphasis on its biochemistry.

Knowledge and understanding of common diagnostic

procedures.

Knowledge of the appropriate use of laboratory techniques.

Knowledge and understanding of the principles of Evidence

Based Medicine.

Knowledge and understanding of molecular, biochemical, and

cellular mechanisms of maintaining homeostasis.

Knowledge and understanding of the clinical presentation ofcommon diseases and conditions.

Knowledge and understanding of the most frequent clinical and

laboratory manifestations of common diseases.



Interpret the results of commonly used diagnostic procedures.

The ability to apply the appropriate use of laboratory methods in

identifying diseases or health problems.

The ability to seek help, when needed, to deal with academic,

personal, or interpersonal problems.

Knowledge and understanding of the need and value of

consultations and referrals. Knowledge and understanding of the

ways of continuous improvements, self-reflection, critical self-

appraisal and lifelong learning.

Recognition of the need to engage in lifelong learning and the

commitment to engage in lifelong learning in order to maintain

sufficient familiarity with scientific advances to ensure they are

integrated appropriately with patient care.

The ability to recognize personal educational needs, to selectand utilize appropriate learning resources, apply principles of

evidence based medicine, the capacity to recognize and accept

limitations in one’s knowledge and clinical skills, and a

commitment to continuously improve one’s knowledge and

ability.



The ability to critically appraise the medical literature.

The ability to demonstrate personal responsibility, reliability,

dependability, open-mindedness, and curiosity.

Effective communication skills: besides English language

proficiency, to demonstrate the capability to utilize verbal and

non-verbal communication specific to culture, gender, and

patient understanding.



At the end of each monthly block there will be a

review lecture and may be oral presentation

sessions where they fit.

All students are expected to do oral presentations

during the semester and the credit varies fromblock to block.

There may be quizzes depending on the faculty.

Guidelines on the Do’s and Don’t’s of how to do a

presentation are in the Research in Health and

Medicine 1 (RHM1) course.



And now a bit about me.

Born a long time ago in a far off place -London, UK.

Lived in South Africa (now citizen and my home)for 32 years.

Accent still a bit British, but Afrikaans andStrine thrown in as well.

Avid conservationist and represented SouthAfrica several times at CITES and IUCN.

Rock DJ for more than 40 years, recentlypacked it in ‘cos Anguilla ain’t the place.



Son and daughter left SA in 2001.

Daughter in London teaching.

Son in Pasadena as environmental consultant.

Ex-wife somewhere back in London.

Cat came with me.

I don’t like titles, so I go by the name ofBruce.



Now for somehome truths.

Just how big is

Africa?

>30 million squarekilometers, >20%of total land area.

Algiers (A) toCape Town (C)is 8000km/5000m.

Nairobi (N) toCape Town (C)is 4100km/2600m.

Boston to Seattle?4000km/2500m.

A

C

N



So it is BIG! And it’s also high!Most of the central Africanplateau is around 1500m up inthe air!

Even South Africa is big andexcept for the coast is high.

Messina to Cape Town is over2000km.



LIPIDS IN HUMAN HEALTH AND DISEASE.



NUTRITION OF FELINAE.



NUTRITION OF CARCHARIFORMES.



I took early retirement from Wits in South

Africa, initially went to Bonaire, but then camehere to teach and get very wet sometimes.



THE END

Introduction Biochem Fall 2014

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