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PHS2104 > Lecture 7 > Flashcards

Lecture 7 Flashcards

1
Q

Where are hormones released into?

A

The bloodstream

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2
Q

Fill in the blanks:
Most hormones are _____ in nature

A

Protein
notable exception: steroid hormones

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3
Q

Why is it harder to design small molecular weight chemicals to mimic the biological activity of the hormones?

A

Many peptide (protein) hormones make physical contact with their respective receptors through a large surface which makes it much harder to design small molecular weight chemicals to mimic the biological activity of the hormones.

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4
Q

Amine hormones are derivatives of which amino acids?

A

Tyrosine or tryptophan

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5
Q

What is an example of an amine hormone derived from tyrosine?

A

Norepinephrine, catecholamines

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6
Q

What is an example of an amine hormone derived from tryptophan?

A

Melatonin

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7
Q

What is the general modification done to amine hormones?

A

The carboxyl group is removed while the amine group stays

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8
Q

What are steroid hormones derived from

A

Cholesterol

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9
Q

Which hormone has the longest half life? amine peptide or steroid

A

Steroid

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10
Q

How do steroid hormones travel to the target cell?

A

They are bound to a transport protein

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11
Q

What is the pathway of hormone action for water soluble hormones?

A
  1. The hormones bind to membrane receptors on the cell surface
  2. The binding activates a G protein
  3. The activated G protein actives adenylyl cyclase
  4. Adenylyl cyclase catalyses the conversion of ATP to cAMP which is a secondary messenger
  5. cAMP actives protein kinases
  6. These protein kinases phosphorylate proteins in the cytoplasm, which activates them, allowing them to alter cell activity.
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12
Q

What is the pathway of hormone action for lipid soluble hormones?

A
  1. Lipid soluble hormones diffuse through the plasma membrane
  2. They bind to the receptor within the cytoplasm forming a receptor-hormone comples
  3. The receptor hormone complex enters the nucleus and triggers gene transcription
  4. The transcribed mRNA is translated into proteins that alter the cell activity
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13
Q

What are some second messengers used in a cell signalling pathway?

A

cAMP, Ca2+ ions

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14
Q

What are the amino acid resides that get phosphorylated in a protein and what allows them to be phosphorylated?

A

Serine, threonine and tyrosine residues
They all have an -OH group

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15
Q

What is another name for the human growth hormone and what kind of hormone is it

A

Somatotropin
Peptide hormone

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16
Q

How does the growth hormone work?

A
  1. The hypothalamus releases growth hormone releasing hormone
  2. GHRH stimulates the pituitary gland to release growth hormone
  3. GH stimulates the liver to release insulin like growth factor 1 which acts on the bone, skeletal muscle and adipose tissue
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17
Q

What is the function of the growth hormone during fasting?

A

It stimulates the switch from glucose to fatty acids as a source of fuel during fasting

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18
Q

What hormone inhibits the release of growth hormone from the pituitary gland and where is is secreted from?

A

Somatostatin
Hypothalamus

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19
Q

Which cell is used to produce recombinant growth hormone?

A

E coli

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20
Q

What kind of dimer is the growth hormone receptor?

A

Homodimer

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21
Q

Explain the signalling pathway of the growth hormone.

A
  1. The receptor is a homodimer (2 of the same subunits come together and bind)
  2. The subunits are brought together by the binding of the receptor.
  3. Once the receptor is activated, it phosphorylates proteins like STAT5 STAT5 dimerises / STAT1 and STAT3 dimerise
  4. They enter the nucleus and then change the transcription.
22
Q

What are some off label uses for growth hormone?

A

athletic performance and anti-ageing.

23
Q

What are some detrimental effects that may arise from the misuse of growth hormone?

A

Cancer, acromegaly, fluid retention, joint pain and type II diabetes.

24
Q

What is the process by which insulin is produced in vivo?

A
  1. Beta cells in Islets of Langerhans of the pancreas produce pre-proinsulin (110 AA) that contain a 24 AA amino-terminal signal sequence
  2. The signal peptide is cleaved off to form proinsulin in the ER
  3. C peptide is cleaved in the Golgi
  4. Mature insulin consists of chain A (21 amino acids) and chain B (30 amino acids), joined by 2
    disulphide bonds
25
Q

What happens to the body when there is no insulin?

A
  1. Glucose cannot enter the cells to
    make energy.
  2. Without glucose, the cells of the body have no energy and they become tired very quickly.
    This decreases energy for tasks in everyday life.
  3. Since glucose can’t enter the cells, it remains unused and stays in the bloodstream, thus leads to high blood glucose levels.
  4. The body attempts to get rid of the extra glucose building up in the bloodstream by sending it out in the urine. People with untreated or poorly controlled diabetes frequently urinate large amounts. They will also drink large quantities of water to replace the
    fluid lost.
26
Q

What are the types of diabetes and what are they caused by?

A
  1. Type 1: decreased or complete absence of insulin
  2. Type 2: Beta cell defect or decreased tissue sensitivity to insulin (insulin resistance)
  3. Type 3 (gestational): Not sufficient insulin produced or reduction in tissue sensitivity
27
Q

What are the symptoms and effects of diabetes?

A

Clinical & metabolic features:
Hyperglycemia
Polyuria (frequent urination), polydipsia (frequent thirst) and polyphagia (frequent hunger) (the 3Ps)
Ketoacidosis (diabetic coma) → When the body breaks down fats instead of glucose for fuel. A byproduct of this is ketones that cause ketoacidosis.
Long term effects
Vascular diseases – diabetic retinopathy, coronary artery, cerebrovascular or peripheral vascular deficiency
Kidney disease
Infections

28
Q

What does the blood test do to detect diabetes?

A
  1. Hemoglobin A1C, HbA1C
  2. With a lot of glucose, over time, the glucose will coat the haemoglobin so they’re testing for that. This takes 2-3 months.
29
Q

What are advantages and disadvantages of the urine test for diabetes?

A

Advantage: Quick, non-invasive, safe for practitioner
Disadvantage: Inaccurate

30
Q

What are advantages and disadvantages of the blood test for diabetes?

A

Advantage: More sensitive and accurate
Disadvantage: Higher cost, Pain, More complicated procedure

31
Q

What are the treatments given to people with type II diabetes?

A

First line: diet, exercise, weight reduction
Second line: oral medications to promote release of insulin, reduce production of glucose by liver or increase cell sensitivity to insulin
Third line: Insulin

32
Q

What is the mechanism of action of drugs that target the pancreas to treat diabetes?

A

They increase the insulin secretion from pancreatic beta cells

33
Q

What is the mechanism of action of drugs that target the liver and muscle cells to treat diabetes?

A
  1. It decreases hepatic glucose production and increases glucose sensitivity
  2. It increases insulin sensitivity in the muscle, fat and liver
34
Q

What is the mechanism of action of drugs that target the GI tract to treat diabetes?

A

It decreases the rate of carbohydrate digestion so less glucose is produced

35
Q

What are the ways by which insulin can be produced?

A
  1. Extraction from human/animal pancreas
  2. Chemical synthesis from individual aa (low yield, high cost)
  3. Conversion of pork insulin (1 aa difference) or “semisynthesis” (not applicable for all markets)
  4. Fermentation of genetically engineered microorganisms
36
Q

What are the steps to purity recombinant

A
  1. Human proinsulin is isolated from the e coli
  2. It’s purified using chromatographic purification (gel filtration and ion exchange)
  3. The purified proinsulin is subjected to proteolytic cleavage to produce crude insulin
  4. The crude insulin is purified by ion exchange chromatography to remove C-peptide, enzyme trypsin and carboxypeptidase and unfolded proinsulin
  5. It is crystallised using zinc chloride
  6. It’s purified again using HPLC to remove structurally similar insulin-like components
  7. It’s further purified by gel filtration to yield Highly purified recombinant human insulin
37
Q

What is the purpose of basal level insulin secretion?

A

To suppress lipolysis, proteolysis and hepatic glucose metabolism

38
Q

What are the types of injectable insulin?

A
  1. Rapid acting
  2. Short acting
  3. Intermediate acting
  4. Long acting
  5. Prolonged action analogue
39
Q

What are the types of rapid acting insulin?

A

Insulin Lispro
Insulin aspart
Insulin glulisine

40
Q

What is the modification done to Insulin lispro?

A

Original B28 Pro and B29 Lys reversed to
resemble insulin-like growth factor

41
Q

What is the modification done to Insulin aspart?

A

B28 Pro replaced with aspartic acid

42
Q

What is the modification done to Insulin glulisine?

A

B29 Lys replaced with Glu
B3 Asn replaced with Lys

43
Q

Which of the rapid acting insulins are hexameric like normal insulin?

A

none

44
Q

Where are short acting regular insulin obtained from?

A

Before used to be obtained from pig and cow pancreas
Porcine insulin was chemically converted into human insulin.
Now, recombinant insulin has largely replaced animal insulin

45
Q

What are examples of intermediate acting insulin?

A

Neutral Protamine Haegdorn (NPH)
Lente (discontinued in 2000s)

46
Q

What is Neutral Protamine Hagedorn (NPH) composed of?

A

It is a neutral crystalline suspension which is made of a co-crystallization of insulin with protamine (basic 30 amino-acid peptide) in phosphate buffer.

47
Q

What are examples of Long-acting Insulin

A

Insulin Glargine
Insulin Detemir

48
Q

How is insulin modified to produce insulin glargine and why is that modification beneficial?

A
  1. Human insulin with Asn21 replaced with Gly, together with 2 Arg added to the C-terminus of chain B
  2. This structural modification shifts the pI from 5.4 to 6.7 – more soluble in acid pH and less soluble in neutral pH of subcutaneous tissue
49
Q

How do the properties of insulin glargine make it long acting?

A
  1. Upon subcutaneous administration, the insulin precipitates out of solution in the neutral environment
  2. The precipitate provides a prolonged release of insulin over 24h without a pronounced peak.
50
Q

How is normal insulin changed to form insulin detemir?

A

Devoid of insulin B30 Thr residue
C14 fatty acid covalently attached to B29 lysine

51
Q

Why is a fatty acid attached to B29 lysine in insulin detemir?

A

It allows the insulin to bind to albumin which allows it to persist longer in the blood and exert its effects for longer.

52
Q

What are all the FDA approved indications for Human Growth Hormone?

A
  1. Growth hormone deficiency
  2. Growth failure due to chronic renal insufficiency
  3. HIV/AIDS wasting
  4. Idiopathic short stature
  5. Nooman syndrome
  6. Prader-Willi syndrome
  7. Short bowel syndrome
  8. Small for gestational age infants
  9. Short stature homebox containing gene deficiency
  10. Turner syndrome

PHS2104 (15 decks)

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