Lecture 1: Characteristics of Biomolecules in Health and Disease

Question 1

Major biomolecules that play important roles in cellular functions

Answer 1

Water
Carbohydrates (glucose)
Proteins (amino acids)
Lipids (fatty acids, triglycerides) Sodium
Potassium
Calcium
Bicarbonate
Chloride
Lactate
Pyruvate
Acetyl CoA (acetyl coenzyme A

Question 2

Other major biomolecules

Answer 2

Calcium
Bicarbonate
Chloride
Lactate
Pyruvate
Acetyl CoA
Oxaloacetate

Question 3

Functions of biomolecules

Answer 3

1. Responsible for producing energy through catabolic reactions
2. Involved in using up energy for the synthesis of macromolecules through anabolic pathways.
3. Useful as micronutrients in the maintenance of health and management of
   patients.
4. Important in cellular functions that maintain life.
5. Important as structural components.

Question 4

Biomolecules are vital constituents of the human body and are responsible for

Answer 4

1. Supplying ATP/energy through catabolism of dietary nutrients.
2. The synthesis of macromolecules through anabolic pathways (e.g. gluconeogenesis) in cells, using the energy derived from the catabolism of nutrients
3. The metabolism of vitamins and micronutrients.
4. Maintaining optimal and specific cellular environments
5. Controlling specific homeostatic mechanisms in cells

Question 5

Functions of carbohydrates

Answer 5

Immediate source of energy

Structural molecules

Interact with proteins (glycoproteins) and lipids (glycolipids)

Question 6

What happens to excess glucose in hyperglycemic patients?

Answer 6

i.e.. diabetes

Excess glucose binds to proteins

Leads to microvascular diseases (atherosclerosis (narrowing and hardening of arteries), nephropathy (kidney disease) and neuropathy (loss of sensation))

= multi-organ failure

Question 7

What happens when excess glucose binds to hemoglobin in hyperglycemic patients?

Answer 7

Affects Hb’s ability to carry oxygen.

Indicated by A1C value, which is a measure of hyperglycaemia

Question 8

Three main effects of hyperglycemia

Answer 8

Osmotic effect

Protein glycosylation

Radical effect

Question 9

What does osmotic effect cause?

Answer 9

Dehydration of cells

Result of movement of water from cells (low concentration, low osmotic pressure) into blood plasma (high concentration, high osmotic pressure)

Question 10

What happens when there is dehydration of brain cells?

Answer 10

Coma

Question 11

What is osmotic pressure?

Answer 11

The pressure that needs to be applied to a solvent to prevent is from moving to another compartment by osmosis

Question 12

What does osmotic effect cause in diabetic patients with hyperglycaemia?

Answer 12

Polyuria (frequent urination)

Thirst

Glycosuria (excess glucose in urine, which leads to excess water excretion in urine as well)

Question 13

What is the radical effect?

Answer 13

Outcome of hyperglycaemia

Excess glucose can produce reactive oxygen species, which damage cell membrane, DNA and other molecules

Question 14

What can happen to excess glucose?

Answer 14

Can be converted to glycogen (glycogenesis) in liver and muscles

This serves as a reserve for when there is not enough glucose

Question 15

What is glycogenolysis?

Answer 15

When the liver breaks down glycogen into glucose to supply extra hepatic tissues with glucose

Liver doesn’t use much glucose itself so that there is some for other organs

Question 16

When is muscle glucose broken down?

Answer 16

During exertion, when energy production is needed

Question 17

What lipids can glucose be converted into?

Answer 17

Triglycerides in liver

Fatty acids

Question 18

Can fatty acids be converted to glucose?

Answer 18

NO (thermodynamic issue)

Question 19

How does body maintain glucose levels (homeostasis)?

Answer 19

Synthesizes it from other molecules during gluconeogenesis

Question 20

Where do erythrocytes get energy? And what happens if they do not have energy?

Answer 20

Depend entirely on glucose

Deficiency of energy = destruction/lysis/breakdown?

Question 21

Where do brain cells get energy under normal conditions?

Answer 21

Entirely from glucose

Question 22

Where do brain cells get energy during fasting and starvation?

Answer 22

Ketone bodies derived from oxidation of fatty acids

Lack of glucose = unconsciousness and eventually coma

Question 23

What molecules can glucose be synthesized from during gluconeogenesis?

Answer 23

Glycerol

lactate

Amino acids

Question 24

Where does gluconeogenesis occur?

Answer 24

Liver and Kidneys only

Question 25

How are lactate and oxaloacetate produced from glucose?

Answer 25

Glucose -> pyruvate pyruvate -> lactate and oxaloacetate

Question 26

How is acetyl CoA produced from glucose?

Answer 26

Glucose -> pyruvate pyruvate -> acetyl CoA

Question 27

How is glucose produced from pyruvate?

Answer 27

Pyruvate -> oxaloacetate Oxaloacetate -> glucose

Question 28

What can disorders in glucose metabolism (breakdown) lead to?

Answer 28

Hypertriglyeridemia (accumulation of triglycerides) Hepatomegaly (enlarged liver) due to accumulation of glycogen Lactic acidosis (due to inhibition of oxidative phosphorylation)

Question 29

What are triglycerides?

Answer 29

Glycerol + fatty acids

Question 30

Where are triglycerides found?

Answer 30

Adipose tissues or chylomicrons

Question 31

Functions of triglycerides

Answer 31

Most useful form of storage energy Energy source in absence of glucose Membrane structures in lipid bilayer Interact with proteins and carbohydrates

Question 32

What can the metabolization of fatty acids be used for?

Answer 32

To produce energy and ketones

Question 33

When and why do certain organs use ketones for energy?

Answer 33

Muscles, brain, liver, kidney Used during fasting

Question 34

Fatty acids can be converted to...

Answer 34

Acetyl CoA (the reverse is true as well) Triglycerides (interactions with glycerol)

Question 35

What happens when there is a disorder in catabolism of fatty acids?

Answer 35

lack of energy hypertriglyceridemia fatty degeneration of the liver during fasting can be fatal because of the lack of glucose.

Question 36

Why is fatty acid oxidation important for glucose synthesis?

Answer 36

Oxidation of FAs produces ATP that is used in anabolic pathways for glucose synthesis (gluconeogenesis in liver) from glycerol, amino acids and lactate If there is no FA oxidation during fasting, glucose cannot be produced and organs will fail

Question 37

Functions of proteins

Answer 37

enzymes hormones other signaling molecules

Question 38

Are proteins a storage form of energy?

Answer 38

NO But, they can be broken down to amino acids, which can be converted to acetyl coA and metabolized to produce ATP Proteins can be broken down to amino acids, which can be converted to glucose in the liver.

Question 39

What happens to the blood when Red blood cells lyse?

Answer 39

High lactate in the blood

Question 40

What are essential amino acids?

Answer 40

provided externally to the body

Question 41

What are non essential amino acids?

Answer 41

produced in the body from essential amino acids.

Question 42

Glucogenic amino acids

Answer 42

can be converted to glucose only via pyruvate Other amino acids can be either glucogenic or ketogenic, depending on the physiological conditions.

Question 43

Ketogenic amino acids

Answer 43

can be converted to ketones only via acetyl coA Other amino acids can be either glucogenic or ketogenic, depending on the physiological conditions.

Question 44

Breakdown of proteins

Answer 44

Proteins -> amino acids -> ammonia Ammonia is neurotoxic, and is converted to urea in the liver

Question 45

What excretes urea?

Answer 45

Kidneys

Question 46

What happens when someone has a disorder in protein/amino acids metabolism?

Answer 46

Can lead to high levels of ammonia (hyperammonaemia), which can adversely affect the central nervous system and causes developmental delays.

Question 47

What is calcium important for?

Answer 47

muscle contraction

Question 48

What is calcium phosphate important for?

Answer 48

bone formation

Question 49

What are sodium and potassium important for?

Answer 49

maintaining the sodium-potassium gradient to propagate action potentials/nerve impulses

Question 50

What are bicarbonate ions important for?

Answer 50

act as buffer system to reduce acidity

Question 51

What are Chloride ions important for?

Answer 51

allow for osmotic effect and hence flow of water.

Question 52

What are trace elements important for?

Answer 52

functions of cellular proteins and processes. vitamins and minerals are important as cofactors and coenzymes for enzymatic activities

Question 53

What is the central molecule that connects the metabolic pathways of proteins, carbohydrates and lipids?

Answer 53

Acetyl CoA Also, all dietary nutrients and proteins can be converted to acetyl coA (see figure)

Question 54

What does acetyl-CoA interact with in TCA?

Answer 54

Oxaloacetate Forms carbon dioxide, water, energy and reduced coenzymes (NADH)

Question 55

How is pyruvate linked to the TCA/Krebs cycle

Answer 55

Via acetyl CoA

Question 56

How can triglycerides be converted to glucose?

Answer 56

Triglyceride is broken down into glycerol and fatty acids, then glycerol is converted to glucose in the liver

Question 57

How does hyperglycemia leads to diabetic foot ulcer?

Answer 57

interaction of glucose with proteins leading to glycosylated proteins. glycosylated proteins produce deleterious effects in different tissues leading to peripheral neuropathy, nephropathy, and optic neuropathy, and cardiovascular diseases.

Question 58

What does fatty degeneration of muscles lead to?

Answer 58

Muscle damage Myalgia (muscle pain) Myoglobinuria (myoglobin in urine) Respiratory distress (release of ion from Mb that can radicalize and oxidize proteins) Kidney stones (precipitates formed by Mb)

Question 59

What does abnormal lipid metabolism cause?

Answer 59

Fatty liver disease Enlarged due to fat deposits

Question 60

What does pyruvate link to gluconeogenesis?

Answer 60

Lactic acid Oxaloacetate