2. Biochemistry - Nate

Question 1

PKU

1. Full name?
2. Type of metabolism error?
3. Cause?
4. Role of this enzyme?
5. What kind of nutrient is phenylalanine?
6. What can phenylalanine build up lead to?
7. Best proven treatment?
8. Type of genetic disease?
9. Why is the baby alright whilst in the mothers belly?
10. What is phenylalanine normally broken down into? Why is this important?
11. What can excessive phenylalanine be metabolised into?
12. Give examples of 3 foods high in phenylalanine

Answer 1

1. Phenylketonuria
2. Inborn error of metabolism
3. Absent / virtually absent phenylalanine hydroxylase (PAH)
4. Break down excess phenylalanine from food
5. Protein
6. Build up in blood and brain to toxic levels, affecting brain development + function
   This can lead to intellectual disability, seizures, hypopigmentation, hyperactivity and other serious medical problems
7. Phenylalanine restricted diet
8. Inherited recessive problem
9. The mothers body can break down phenylalanine
10. Other essential compounds especially tyrosine, which is an essential amino acid so needs to be in diet. Tyrosine is used for producing neurotransmitters like dopamine + epinephrine
11. Phenylketones
12. Chicken breast / egg whites / tuna

Question 2

State 2 overall reasons why signs and symptoms are caused in inborn errors of metabolism

Answer 2

1. Toxic accumulation of substrate behind block

2. Deficiency of product after block

Question 3

Describe the diagram which highlights the theoretical consequences of an enzyme deficiency

Answer 3

Defective enzyme in the middle

On left:
Substrate (increased)
Metabolites (increased)
Leads to box saying effect on other metabolic activity

On right:
Products (decreased)
Metabolites (decreased)
Leads to box saying effect on other metabolic activity

In the middle (under defective enzyme):
Circle = co factor A - action - co factor B - other enzymes
Both cofactors leads to box saying effect on other metabolic activity

Question 4

State the 2 theoretical consequences of an enzyme deficiency

Answer 4

1. Increased substrate = toxic effect

2. Decreased product = insufficiency

Question 5

State 4 ways to test for a metabolic disease

Answer 5

1. Test blood/bodily fluid for presence of substrate
2. Genetic testing / genomic testing for specific base pair changes
3. Test for decreased product
4. Check level of enzyme / measure enzyme activity

Question 6

1. What is is called when someone has low oxygen?
2. Which fuel metabolism pathway will they use and why is this a problem?
3. How long can cells go without running oxidative phosphorylation? What cells is this particularly important in?

Answer 6

1. Hypoxia
2. Glycolysis - less efficient at making ATP
3. 1.5 mins
   High energy demand cells

Question 7

Low oxygen = do glycolysis

1. What do you end up with?
2. What 2 things can you not go further into?
3. What accumulates as a result of this?
4. What is it used for? If you convert it into lactate, what can you regenerate? What is the enzyme that is involved called?
5. What process can now continue as there is no accumulation?

Answer 7

1. Pyruvate
2. Acetyl co-A / TCA cycle
3. Pyruvate
4. Anaerobic respiration
   NAD+
   Lactate dehydrogenase
5. Glycolysis

Question 8

Name the uses of lactate in the liver and in muscle(including cardiac muscle)

Answer 8

Liver = generate glucose via gluconeogenesis
Muscle = provide Pyruvate for TCA cycle

Question 9

High levels of lactate

1. What does it reduce?
2. What does this then lower?
3. Give 2 examples of this

Answer 9

1. Blood pH
2. Oxygen carrying capacity of blood cells
3. Severe anaemia / alcohol intoxication

Question 10

Decreased blood flow results in decreased oxygen

1. What does this reduce?
2. So the synthesis of what is decreased?
3. Which pump is disrupted?
4. What is increased leading to myocytes swelling?
5. There is an influx of which ion? This activates what? This disrupts what? What is the final outcome?
6. There is also an increased production of what kind of atom?

Answer 10

1. ATP
2. ATP synthesis
3. Na/K ATPase pump
4. Cell membrane permeability
5. Calcium influx = activates proteases = disrupt cell function = cell death
6. Free radicals

Question 11

What 2 things do free radicals cause

Answer 11

Lipid peroxidation = membrane disruption

Protein damage = cellular dysfunction

Question 12

Ischaemia

1. If there is reduced oxygen and reduced nutrients, what else is there a reduction of?
2. This leads to which kind of fuel metabolism? What occurs as a result of this?
3. What does this ultimately lead to? Give 4 examples of things that cause this
4. Finally, all these things can lead to what? By which 2 methods?

Answer 12

1. Reduced ATP
2. Anaerobic metabolism = acidosis in cells
3. Loss of cellular homeostasis
   Leaky membrane / Sodium potassium pump failure / cellular swelling / calcium influx
4. Cell death via apoptosis or necrosis

Question 13

What 2 features of a myocardial protein will determine the time course of the bio marker appearance in general circulation?

Answer 13

Size

Sub cellular distribution

Question 14

After an infarction:

1. What is released within the first few hours?
2. What is released within 2-6 hours?
3. What is released within 12-24 hours?

Answer 14

1. Ions
2. Metabolites
3. Macromolecules

Question 15

Name the 4 aspects of an ideal cardiac marker, giving it a brief description

Answer 15

1. High sensitivity
   High concentration released after myocardial injury
2. High specificity
   Absent in non-myocardial tissue
3. Good analytical characteristics
   Measurable by cost-effective method
4. Good clinical characteristics
   Influence therapy and improve patient outcome

Question 16

Ideal cardiac marker = high sensitivity

1. Define
2. For early diagnosis?
3. For late diagnosis?

Answer 16

1. High concentration in myocardium released after myocardial injury
2. Rapid release
3. Long half-life in blood

Question 17

Ideal cardiac marker = high specificity

1. Define
2. Non-diseased subjects?

Answer 17

1. Absent in non-myocardial tissue

2. Not detectable in blood

Question 18

Ideal cardiac marker = analytical characteristics

1. Define
2. Complexity?
3. Turnaround time?
4. Precision and accuracy?

Answer 18

1. Measurable by cost-effective method
2. Simple
3. Rapid
4. Sufficient precision and accuracy

Question 19

Ideal cardiac marker = clinical characteristics

Define

Answer 19

Able to influence therapy and improve patient outcome

Question 20

Name the 3 cardiac markers used in order of appearance

Answer 20

Myoglobin
CK-MB
Cardiac troponin (I or T)

Question 21

1. When does myoglobin disappear?
2. When does CK-MB disappear?
3. When does Troponin (T or I) disappear?

Answer 21

1. Within 24 hours
2. Within 2-3 days
3. Within 5-15 days

Question 22

There is no ideal cardiac marker

1. Which one is used for sensitivity because of its early onset (however it is not cardio-specific)?
2. Which one if used for specificity because it is cardio-specific?

Answer 22

1. Myoglobin

2. Cardiac troponins

Question 23

Too much LDL in circulation

1. What does it interact with?
2. What does this lead to?
3. Core?
4. Plaque?
5. Explain a complicated plaque

Answer 23

1. Foam cells
2. Fatty streak
3. Lipid core
4. Atherosclerotic plaque
5. Complicated atherosclerotic plaque: plaque rupture / thrombosis / haemorrhage

Question 24

Name 6 risk factors of atherosclerosis

Answer 24

1. Hyperlipidaemia
2. Coagulation
3. Diabetes
4. Genetics
5. Age
6. Lifestyle

Question 25

Lipoprotein metabolism and increased clotting 1. What 2 cells are circulating? 2. What kind of deposits on blood vessels? 3. What kind of plaques do they turn into? 4. What can happen to these plaques which triggers clotting? 5. What can the two outcomes be?

Answer 25

1. Foam cells + LDL 2. Fat deposits 3. Lipid rich plaques 4. They can disrupt - they have rough surfaces - can trigger clotting 5. Completely occlusive thrombus or partially occluded thrombus

Question 26

1. What happens in a completely occlusive thrombus? | 2. What happens in a partially occluded thrombus?

Answer 26

1. Blood supply shut off | 2. Resolve some of clot = fibrous fatty end result

Question 27

Define embolus

Answer 27

Object from another part of the body that obstructs blood flow

Question 28

Define thrombus

Answer 28

Blood clot that becomes an embolus

Question 29

1. What do vascular endothelial cells normally secrete? Give 2 examples and explain the relation to clot formation 2. If there is damage to smooth muscle cells in the vessel wall, what can happen? Explain the relation to clotting

Answer 29

1. Vasodilators / PG + NO / inhibits clot formation | 2. Vasoconstriction / promotes clotting

Question 30

1. When damage results in exposure of the basement membrane, what 2 things is blood exposed to? 2. When damage results in exposure of vessel wall, what is blood exposed to? 3. When damage results in exposure of loses epithelial cells, what is blood exposed to?

Answer 30

1. Collagen + subendothelial tissue factor 2. Platelet activating factor 3. ADP

Question 31

Activated platelets 1. What are the 2 reasons they change shape for? 2. What 3 reasons do they activate other molecules for? 3. What do they adhere to? 4. What is the initial plug?

Answer 31

1. Facilitate movement + aggregation 2. Activate other molecules / allow adhesion / cause vasoconstriction 3. Vessel wall at damage site 4. Platelet aggregation

Question 32

Name 5 things that can activate platelets

Answer 32

``` ADP Collagen Thrombin Immune complexes High physical shear force ```

Question 33

How clotting factors work 1. Stage the names of the 3 pathways 2. What is the intrinsic pathway activated by? 3. What is the extrinsic pathway activated by? 4. What kind of state do all clotting factors start out in?

Answer 33

1. Intrinsic pathway, extrinsic pathway and common pathway 2. Collagen 3. Tissue factor (from tissue injury) 4. Inactive state

Question 34

Clotting cascade 1. Describe the main aspect of the clotting cascade 2. What 2 things bind to and inactives thrombin immediately? What does this stop?

Answer 34

1. Prothrombin to thrombin Thrombin transforms fibrinogen to fibrin to cross linked fibrin 2. Anti-thrombin and protein C = both stop clotting

Question 35

1. What system breaks down fibrin clots? 2. Via which serine protease? What is the name of the inactivate state it circulates the plasma in? 3. What 2 things allow the activation of this serine protease? 4. What inhibits this activation? 5. What is the end result?

Answer 35

1. Fibrinolytic system 2. Plasmin Inactive form = plasminogen 3. tPA = tissue type plasminogen activator uPA = urinary type plasminogen activator 4. Plasminogen activator inhibitor 5. Fibrin degraded = clot broken up