Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biopharmaceutical Science > Therapeutic Hormones > Flashcards

Therapeutic Hormones Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

What are true endocrine hormones?

A

Substances synthesized and released from a specific gland in the body that, by interacting with a receptor present on a distant sensitive cell, brought about a change in that target cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some hormones that fit into the grouping of true endocrine hormones?

A

Insulin, glucagon, growth hormone (GH), and gonadotrophins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is insulin?

A

Insulin is a polypeptide hormone produced by the beta cells of the pancreatic islets of Langerhans and plays a central role in regulating blood glucose levels, keeping it within the range of 3.5-8.0 mmol/L.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the role of insulin in regulating blood glucose levels?

A

Insulin stimulates glucose transport into cells, thus reducing their blood concentration.
It also

  • stimulates intracellular biosynthetic (anabolic) pathways, such as glycogen synthesis,
  • inhibits catabolic pathways, such as glycogenolysis,
  • stimulates DNA and protein synthesis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the most important targets of insulin?

A

Skeletal muscle fibers, hepatocytes, and adipocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the most potent stimulus of pancreatic insulin release?

A

An increase in blood glucose levels, usually after mealtimes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does insulin orchestrate a metabolic response to the absorption of glucose and other nutrients?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is diabetes mellitus?

A

A disease that occurs when the body fails to produce or properly use insulin, resulting in high blood glucose levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is insulin-dependent diabetes mellitus (IDDM)?

A

Type-1 diabetes or juvenile-onset diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What causes IDDM?

A

by T-cell-mediated autoimmune destruction of the insulin-producing beta pancreatic islet cells in genetically predisposed individuals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When was insulin first identified

A

Insulin was first identified in 1921 as an anti-diabetic factor and was introduced clinically in 1922.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When was insulins complete amino acid sequence determined?

A

Its complete amino acid sequence was determined by Fred Sanger in 1951, winning him the Nobel Prize in 1958.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is insulin synthesized?

A

Insulin is synthesized as a single polypeptide precursor called preproinsulin. This 180 aa polypeptide contains a 23 aa signal sequence at the N-terminal region that guides the molecule through the endoplasmic reticulum.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is proinsulin?

A

Proinsulin is a precursor to insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is proinsulin processed?

A
  • Proteolytically processed to yield mature insulin and a 34-aa connecting peptide called the C peptide.
  • The C peptide is further proteolytically modified by removal of a dipeptide from each of its ends.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the structure of mature insulin?

A
  • Mature insulin consists of two polypeptide chains connected by two interchain disulfide bridges.
  • The A-chain contains 21 aa, while the larger B-chain is composed of 30 residues.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How was insulin tradtionally produced for commercial use?

A

Produced by directly extracting it from pancreatic tissue of slaughterhouse pigs and cattle followed by multistep chromatographic purification.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the disadvantages of using insulin extract from slaughterhouse pigs and cattle?

A

Immunogenicity and availability issues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does bovine insulin differ from human insulin, and what is the consequence of using it in humans?

A

Differs by 3 amino acids and can elicit an immunological response in humans, leading to insulin resistance and long-term complications.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why is porcine insulin preferred over bovine insulin for humans

A

Porcine insulin differs from human insulin only by one amino acid and is essentially non-immunogenic in humans, but some of its contaminants can still be immunogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How many people worldwide suffer from diabetes, and how does this imact insulin availability?

A

Approx. 170 million people worldwide suffer from diabetes, this is projected to double by 2030.
Has had a direct impact on insulin availability.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the current annual insulin requirement, and is it expected to increase or decrease?

A

Current requirement has surpassed 5000Kg and continues to grow due to the increasing prevalence of diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the recombinant DNA approach?

A

A technique used in biotechnology to create new DNA molecules by combining segments from difference sources

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

When was human insulin produced by recombinant DNA technology approved for medical use?

A

1982

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What was the first product of recombinant DNA technology to be approved for therapeutic use in humans?

A

Insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What was the initial approach to recombinant insulin production?

A

The initial approach to recombinant insulin production involved inserting the nucleotide sequence coding for the insulin A- and B-chains into two different E. coli cells. The cells were cultured separately, with subsequent chromatographic purification of the respective insulin chains produced. The A- and B-chains were then incubated together under the appropriate oxidizing conditions to promote interchain disulfide bond formation – forming ‘human insulin crb’ (chain recombinant DNA bacteria).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is an alternative approach to producing human insulin using recombinant DNA technology?

A

An alternative approach, developed by Eli Lilly, involves inserting a nucleotide sequence coding for human proinsulin into recombinant E. coli. This is followed by purification of the expressed proinsulin and subsequent proteolytic excision of the C peptide in vitro. Such preparations are termed ‘human insulin prb’ – proinsulin recombinant bacteria.

28
Q

Why has the alternative approach to producing human insulin using recombinant DNA technology become more popular?

A

Largely due to the requirement for only a single fermentation and purification step

29
Q

How has recombinant DNA technology been used to engineer improved insulins?

A

Recombinant DNA technology has facilitated the generation of insulins with modified amino acid (aa) sequences that have altered biological activity. Analogues containing aa substitutions at aa residues that interact with the insulin receptor have been manufactured.

30
Q

What is the effect of converting histidine to glutamate at the B10 position in insulin?

A

The conversion results in an analogue with 5-fold higher activity in vitro.

31
Q

What is the effect of converting histidine to glutamate at the B10 position in insulin?

A

The conversion results in an analogue with 5-fold higher activity in vitro.

32
Q

What is the strategy for generating faster-acting insulins using modified amino acids?

A

Substituting amino acids at the contact points between individual insulin molecules with charged or bulky amino acids promotes charge repulsion or steric hindrance between individual insulin monomers, allowing for faster absorption from the site of injection.

33
Q

What are examples of fast-acting insulin analogues that have been approved for general medical use?

A

Examples include ‘Insulin lispro’ (tradename ‘Humalog’) and ‘Insulin Aspart’ (tradename NovaLog).

34
Q

How does Insulin Aspart differ from native human insulin?

A

Insulin Aspart contains an Aspartate residue at B28, rather than a proline. This single amino acid substitution decreases the propensity of individual molecules to self-associate, ensuring that they begin to enter the bloodstream immediately upon administration.

35
Q

How does Insulin Aspart differ from native human insulin?

A

Insulin Aspart contains an Aspartate residue at B28, rather than a proline. This single amino acid substitution decreases the propensity of individual molecules to self-associate, ensuring that they begin to enter the bloodstream immediately upon administration.

36
Q

What is the strategy for generating longer-acting insulin analogues using modified amino acids?

A

Selected amino acid substitutions have been used to generate insulins that exhibit longer plasma half-lives than the native product.

37
Q

What is an example of a long-acting insulin analogue that has been approved for general medical use?

A

‘Insulin glargine’ (tradenames Lantus, Basalin, or Optisulin).

38
Q

How does Insulin glargine differ from native human insulin?

A

Insulin glargine differs from native human insulin in that the C-terminal asparagine residue of the A-chain is replaced by a glycine residue, and the B-chain has been elongated (from the C-terminal end) by two arginine residues, which increases the molecule’s pI and reduces the pH at which it remains soluble.

39
Q

What is Levemir?

A

Levemir is an alternative engineered long-acting insulin that gained approval in 2004.

40
Q

How does Levemir differ from native insulin?

A

Levemir is devoid of threonine B30 and contains a 14-carbon fatty acid residue covalently attached to the side chain of lysine B29, which ensures constant and prolonged release of free insulin, bestowing upon it a prolonged duration of action of up to 25 hours.

41
Q

How does Levemir differ from native insulin?

A

Levemir is devoid of threonine B30 and contains a 14-carbon fatty acid residue covalently attached to the side chain of lysine B29, which ensures constant and prolonged release of free insulin, bestowing upon it a prolonged duration of action of up to 25 hours.

42
Q

What happens to insulin after s.c. injection?

A
43
Q

What are some alternative approaches to insulin delivery other than direct injection?

A

Alternative approaches to insulin delivery, other than direct injection, include inhalable insulin and infusion systems.

44
Q

What is Exubera and how is it administered?

A

Exubera is a recombinant human insulin marketed by Pfizer that is delivered through inhalation technology produced by recombinant E. coli. It is administered through an inhaler in 1 or 3 mg doses.

45
Q

What is Exubera and how is it administered?

A

Exubera is a recombinant human insulin marketed by Pfizer that is delivered through inhalation technology produced by recombinant E. coli. It is administered through an inhaler in 1 or 3 mg doses.

46
Q

Why was Exubera discontinued?

A

Poor sales

47
Q

Why was Exubera discontinued?

A

Poor sales

48
Q

What is Afrezza and what is its key advantage over Exubera?

A

Afrezza is a rapid-acting inhalable insulin produced by Mannkind Corporation and licensed to Sanofi. Its key advantage over Exubera is that its delivery system is small, sleek, and dosed in units rather than mg – allowing for a more discreet administration process and an easier dosing regimen.

49
Q

What are infusion systems and how do they work?

A

Infusion systems continuously deliver insulin to the patient, mimicking more closely the normal changes in blood insulin levels. The simplest design is the open-loop system, which consists of an infusion pump that automatically infuses soluble insulin subcutaneously via a catheter. Blood glucose levels are monitored manually, and the infusion rate is programmed accordingly.

50
Q

What is a closed-loop system or an artificial pancreas?

A

The closed-loop system or artificial pancreas is a more sophisticated version of the open-loop system. It consists of not only a pump and infusion device but also an integral glucose sensor and computer that

51
Q

What is a closed-loop system or an artificial pancreas?

A

The closed-loop system or artificial pancreas is a more sophisticated version of the open-loop system. It consists of not only a pump and infusion device but also an integral glucose sensor and computer that

52
Q

What is glucagon and where is it synthesized?

A

Glucagon is a single-chain polypeptide of 29 amino acids that is synthesized by the A-cells of the islets of Langerhans (and related cells of the digestive tract).

53
Q

What are the major biological actions of glucagon?

A

The major biological actions of glucagon tend to oppose those of insulin, particularly with regard to metabolism regulation. Its prominent metabolic effect is to increase blood glucose levels (i.e. it is a hyperglycemic enzyme).

54
Q

What is the physiological function of glucagon?

A

The major physiological function of glucagon is to prevent hypoglycemia (i.e. low blood glucose levels).

55
Q

What is the most frequent complication of insulin administration to diabetics, and how is glucagon used to treat it?

A

The most frequent complication of insulin administration to diabetics is hypoglycemia, and glucagon is used to treat it. In addition to treating insulin-induced hypoglycemia, glucagon is also used medically as a diagnostic aid during certain radiological examinations of the stomach and small and large intestine.

56
Q

: How is most glucagon produced today, and what are some of the tradenames of recombinant glucagon products?

A

Most glucagon is produced via recombinant means today. ‘GlucaGen’ is the tradename of a recombinant glucagon produced by Novo Nordisk using an engineered S. cerevisiae strain. Eli Lilly also produces a recombinant glucagon using engineered E. coli.

57
Q

What is human growth hormone and how is it synthesized and regulated in the body?

A
58
Q

What are the biological effects of GH and what conditions result from a deficiency or over-production of hGH?

A

GH primarily displays an anabolic activity. A deficiency in the secretion of hGH during the years of active body growth results in pituitary dwarfism, while over-production of hGH during active body growth results in gigantism. hGH overproduction, after primary body growth has occurred, results in acromegaly, a condition characterized by enlarged hands and feet, as well as course features.

59
Q

What are some therapeutic uses of GH, and why was the use of hGH extracted from human pituitary glands stopped?

A

hGH extracted from human pituitary glands was first used to treat pituitary dwarfism in 1958 and subsequently shown to be effective in the treatment of short stature caused by a variety of other conditions, including Turner’s syndrome, idiopathic short stature, and chronic renal failure. The use of hGH extracted from pituitaries of deceased human donors was stopped in 1985 when a link between treatment and Creutzfeld-Jacob disease (CJD) was discovered - with 13 reported cases. Today, all hGH preparations are derived from recombinant sources.

60
Q

What are some therapeutic uses of GH, and why was the use of hGH extracted from human pituitary glands stopped?

A

hGH extracted from human pituitary glands was first used to treat pituitary dwarfism in 1958 and subsequently shown to be effective in the treatment of short stature caused by a variety of other conditions, including Turner’s syndrome, idiopathic short stature, and chronic renal failure. The use of hGH extracted from pituitaries of deceased human donors was stopped in 1985 when a link between treatment and Creutzfeld-Jacob disease (CJD) was discovered - with 13 reported cases. Today, all hGH preparations are derived from recombinant sources.

61
Q

What is recombinant human growth hormone (rhGH) and how is it produced?

A

Recombinant human growth hormone (rhGH) is a synthetic version of hGH that is currently used for therapeutic purposes. rhGH was first produced in E. coli by Genentech in the early 1980s. The initial recombinant preparations differed from the native human hormone only in that they contained an extra methionine (due to the AUG start codon inserted at the beginning of the gene). Subsequently, a different cloning strategy allowed the production in E. coli of products devoid of this terminal methionine. Native and recombinant forms of the hormone were found to have identical biological activity.

62
Q

What are some diseases associated with transmissible spongiform encephalopathies (TSEs), and how are they transmitted?

A

Kuru, Creutzfeld-Jacob disease (CJD), and Variant CJD (vCJD) are all Transmissible spongiform encephalopathies (TSEs) or prion diseases. Kuru was a neurodegenerative disease transmitted among members of the Foré tribe of Papua New Guinea via funerary cannibalism. CJD appears as sporadic, familial (genetic or hereditary), and infectious forms. vCJD is a zoonotic CJD type which resulted from transmission from bovine spongiform encephalopathy (BSE) through ingestion of contaminated meat products.

63
Q

What are Gonadotrophins?

A

Gonadotrophins are hormones produced by the pituitary gland, as well as reproductive and associated tissues. They play a critical role in regulating reproductive function and the development of secondary sexual characteristics. There are three types of gonadotrophins, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotrophin (hCG). All three hormones are produced as heterodimeric hormones containing an identical α-polypeptide subunit and a unique β-polypeptide subunit that confers biological specificity to each gonadotrophin.

64
Q

What are the physiological effects of FSH in males?

A

In males, FSH targets Sertoli cells, which are found in the walls of the seminiferous tubules of the testis. The major physiological effect of FSH in the male is sperm cell production. Sertoli cells nourish and anchor the spermatids, which are subsequently transformed into spermatozoa during spermatogenesis.

65
Q

What are the physiological effects of FSH in females?

A

In females, FSH mainly targets the granulosa cells of the ovarian follicle. FSH stimulates their division, follicular growth, and development, as well as triggering enzymatic production of glycosaminoglycans and other enzymes involved in estrogen synthesis.

66
Q

What is the medical and veterinary application of gonadotrophins?

A

Given their central role in maintaining reproductive function, gonadotrophins have therapeutic potential in treating infertility or subfertility in humans. Menotrophin (human menopausal gonadotrophin) is the name given to FSH-enriched extracts from human urine, which is used in the treatment of anovulatory infertility. In females, menotrophins and hCG are used to stimulate follicular maturation, with subsequent administration of hCG to promote ovulation and corpus luteum formation.

In animals, gonadotrophins are used to induce a superovulatory response in valuable animals, such as thoroughbred racehorses. Gonadotrophins usually utilized to induce a superovulatory response include porcine FSH (p-FSH) and porcine LH (p-LH), which are extracted from the pituitary glands of slaughterhouse pigs. The embryos are then recovered from the animal and maintained in cell culture for a short period. A single embryo is usually re-implanted into the donor female, while the remaining embryos are implanted into other recipient animals that act as surrogate mothers, carrying the offspring to term.

67
Q

What is the role of GnRH in gonadotrophin synthesis and release?

A

The synthesis and release of both FSH and LH from the pituitary gland are stimulated by a hypothalamic peptide called gonadotrophin-releasing hormone (GnRH).

Biopharmaceutical Science (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions