Day 3: Amino Acids and Peptides Flashcards

1
Q

What are the three options for the use of Amino Acids (AA) in our body?

A
  1. synthesis of protein and peptides. AA’s are the building blocks of proteins
  2. Synthesis of essential nitrogen containing biomolecules
  3. AA (protein) cant be used as fuel directly. During starvation, some AAs can be converted to glucose or ketone bodies to be used by cells as a source of energy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the bodies more perferred fuel?

A

Glucose: comes from carbs in diet like starch, sucrose, lactose

When low glucose the body burns fat as fuel

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

Can our brain use dietary fats as fuel?

A

No, it cant. so during starvation, some AAs are converted to glucose, fat and some AAs convert to ketone bodies to meet energy needs of the brain.

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

Can protein drugs be delivered orally?

A

No, it will get broken down into single amino acids by our GI system before being absorbed by our body

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

What are proteinogenic amino acids?

A

All the proteins in eukaryotes are composed of 20 different amino acids known as standard amino acids

**The name means that they are present in AA

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

What is the chirality of standard amino acids?

A

they are all chiral expect for glycine

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

what are human proteins composed of?

A

L-amino acids, no exeptions

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

What are proteases?

A

a group of enzymes whose catalytic function is to hydrolyze (break down) proteins by breaking the peptide bonds

also called proteolytic enzymes or proteinases

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

What are the two main groups and the subgroups of amino acids?

A

Main groups: Hydrophobic and Hydrophilic

Subgroups: Charged, Aromatic, Sulf-containing, branched-chain

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

What are the charged amino acids?

A

Negative: Aspartic acid, Glutamic acid

Positive : Lysine, Histidine,, Arginine

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

What are the polar amino acids?

A

Polar (hydrophilic): Tyrosine, Serine, Cysteine, Threonine, Asparagine, Glutamine

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

What are the Non-Polar amino acids?

A

Non-polar (hydrophobic): Glycine, Alanine, Valine, Leucine, Tryptophan, Methionine, Isoleucine, Proline, Phenyl alanine

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

What are the branched-chain amino acids?

A

Valine, Leucine, Isoleucine

BCAAs: May be useful supplement for muscle recovery and immune upregulation

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

What are the Aromatic amino acids?

A

Phenylalanine, Tyrosine, Tryptophan

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

What are the Sulfur-containing amino acids?

A

Cysteine, Methionine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Protein Phosphorylation? (Phosphorylation of amino acids)

A

One of the most important modes of regulation of protein function. (phosphoregulation)

almost all cases of phosphoregulation, the protein switches between active and inactive form.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the three amino acids that can be phosphorylated at hydroxyl residue

A

Serine, tyrosine (major), throenine

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

What are residues?

A

Amino acids that make up, or that are derived from a polymer

Direction is always N-terminal to C-terminal

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

What is a dipeptide?

A

Contains 2 residues

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

What is a tripeptide?

A

Contains 3 residues

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

What is an oligopeptide?

A

contains a few residues

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

What is a nonapeptide?

A

An oligopeptide containing nine amino acid residues

ex: oxytocin

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

what is a polypeptide?

A

Contains many residues

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

What is a protein (in terms of residues)

A

Has many residues (have defined 2D and 3D structure, usually ~40+

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

What are disulfide bonds?

A

These bonds between cysteine residues play a major role in the corsslinking folding and stability of the proteins

These protein crosslinking increases the rigidity, functions and proteolytic resistance

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

What is the ioselectric point (pI) of amino acids, peptides, and proteins

A

its when they carry no net electrical charge (equal numbers of + and - charges).

EX: if a peptide have 2 + and two - charges, overall charge is 0

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

What kind of charge do AAs / peptides / proteins carry at a pH value below the pI

A

A net postive charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What kind of charge do AAs / peptides / proteins carry at a pH value above the pI

A

a net negative charge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Why do you want to know the values of peptides?

A

can be utilized for protein and peptide isolation, identificationa nd delayed absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When are peptides and proteins least soluble in water and whats the clinical implication of this?

A

At their isoelectric points

A peptide with pI 6 will be less soluble than a peptide with a pI 5 at pysiological pH (7.3)

Clinical implication: Long acting insuline Glargine; added modifications which lead to a shift of the pI from pH 5.4 to pH 6.7, making insulin glargine less soluble at physiological pH levels. This retarded its absorption and thereby extended its duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is an essential amino acid and which ones are they?

A

Cannot be synthesized in our body

valine, lysine, typtophan, leucine, methionine, phenylalanine, isoleucine, threonine, hisidine

9 of them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is a nonessential amino acid and which ones are they?

A

We can synthesize in our body

Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Tyrosine, Glutamic Acid, Glutamine, Glycine, Proline, Serine

11 of them

33
Q

What is the recommended daily allowance of protein for a healthy individual?

A

0.36 g “high quality” protein per lb body weight

1 lb = 0.45 kg

34
Q

What is a high quailty protein source?

A

one that contains all the essential amino acids

comes from animal sources ( milk, eggs, and meat)

35
Q

What are “low quality” protein sources?

A

Protein source that is deficient in one of essential amino acids.

Most vegies are low quality but they can be made up for by eating differant types to gain the ones you need

36
Q

During starvation what happens to AAs in the liver?

A

The liver can convert them into glucose to be used by the brain and RBC. they are called glucogenic amino acids.

37
Q

What are ketogenic amino acids?

A

they are AAs that are converted into ketone bodies which can be used as an energu source during starvation.

38
Q

What is a non-standard amino acid?

A

AA naturally present in cells but does not participate in protein synthesis. Some are consituents of peptides, but thye are generated by modification of standard amino acids in the peptide molecule by post-translational modification

39
Q

What is Carnitine?

A

Non-standard amino acid

Our body synthesizes carnitine from lysine. It shuttles fatty acids to the mitochondria for energy production

40
Q

What is creatine?

A

non-standard amino acid

Produced from three standard amino acids (arginine, glycine and methionine)

Its found in muscle; creatine phosphate is high energy molecule, breaks down to produce ATP when needed.

Its secreted in the urine as creatinine

High levels in serum is maker of compromised kidney function; high creatinine kinase in serum is maker of muscle damage

41
Q

What is Hydroxylysine and Hydroxyproline?

A

Non-standard amino acid

Derived from lysine and proline by hydroxylation

these are required to maintain collagen structure.

ONLY non-standard AAs present in peptide

42
Q

What is Taurine?

A

Non-standard amino acid

Derived from cysteine, synthesized in the liver, component of bile salt

Common composition of energy drinks

43
Q

What is the relationship between lysine and cold sores?

A

Lysine suppliments and diets high in lysine and low in arginine have been used to discourage herpes outbreaks

44
Q

What are the pros of peptide drugs?

A

Higher potency: generally very active on their target receptor = high effect at low dose

High Selectivity: Very tight fit into their receptors makes them much more selective than smaller molecules; which means they tend to bind only to their target receptor and therefore are less likely to be associated with serious adverse side effects

Naturally occuring biolgics: better safety. since they are nautrally they are broken down much eaiser and have less accumulation in body tissue and fewer toxicity

45
Q

What are cons of peptide drugs?

A

Short-lived: Short half-life, means that they generally act in the body for only a very short time, 2-30 minutes before being broken down by proteases

Immunogenicity: can induce antibody production in the body

Difficult to administer orally: Most via injection, oral admin leads to degradation and destruction by the digestive system

Low Product stability: Cannot be stored in aqueous solution more than a few days

46
Q

What is the incretin system?

A

When glucose is taken orally, intestinal cells secretes two peptides called incretins

Glucagon-like peptide-1 (GLP-1)

Glucose-dependent insulinotropic peptide (GIP)

47
Q

What does GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) do after they are screted

A

they bind to their own receptors in the pancreatic beta cells to induce insulin secretion

only have a half-life of 1 minute because they are broken down rapidly by protease DPP-4

48
Q

why wouldnt you want to modify or hide specific sequences to imporve peptide drug stability?

A

it can lead to immunogenicity

49
Q

What are the biological barriers associated with the oral delivery of peptide drugs?

A

Oral route is challenging, due to HCL and proteases being designed to break down these polypeptides into small pieces prior to absorption; snake venom generally doesnt work if swallowed because its peptide based and these barriers break it down unlike when it is injected into the skin.

The 2nd barrier is the intestinal absorptive epithelium. most oral drugs given by oral route are absorbed by intracellular passive diffusion. Most of the cell is phopholipid bilayers, with passive diffusion is limited by lipophilic drugs with MW below 700 Da. most peptide drugs are hydrophilic molecules with MW above 3000, making it hard for them to traverse the membrane

50
Q

What is vasopressin and how does it work in diabetes insipidus

A

A peptide antidiuretic hormone, which stimulates re-absorption of water in the kideny, leading to the formation of more concentrated urine

Diabetes insipidus leads to deficit in vasopressin, so people excrete large volumes of urine and always thirsty

51
Q

What is desmopressin?

A

A synthetic modified analog of the missing hormone, vasopressin.

Is given orally and is degraded much more slowly than vasopressin in the body. But why?

  1. relatively small peptide size it can pass thro intestinal epithlium
  2. D-arginine has been introduced in desmopressin to evade protease attack
52
Q

If you have 1 free AA how many ionizable groups will it have?

A

It will have 2 (the amino + charge) and the carboxy - charge

53
Q

Which AA is called Immino and what does it mean?

A

Proline; it means that its side chain inter acts with the amino group to form a ring

54
Q

What does it mean to have a chiral center

A

The alpha carbon has 4 SINGLE BONDS to 4 different things

55
Q

What is the one AA which has no chirality?

A

Glycine

56
Q

What is the chirality of all the AAs in the human body?

A

they are all in the L (left) postion

57
Q

What is the indication if you find D amino acids in a persons poo?

A

it could mean they have a bacterial infection due to the fact humans can not cleave or breakdown D AAs.

58
Q

Where are the D amino acids of bacteria found in the bacteria and why do the bacteria need them?

A

They are found in bacteria cell walls and it allows them to escape digestive enzymes (proteases) = more resistant

59
Q

What does some research show about BCAAs (branched-chained amino acids)

A

It shows that they might be helpful in muscel recovery and immune upregulation

60
Q

What is Selenocysteine?

A

The 21st amino acid. Has anti-oxidant activy.

Unlike the other amino acids this one does not have a free pool in the cell

61
Q

What is pyrrolysin?

A

22nd amino acid. NOT IN EUKARYOTES (PROTEINOGENIC AA)

62
Q

What AA is the most effective as a buffer at physiological pH?

A

Histidine

63
Q

Where does an AA act as a buffer in terms of the pH and pKa value?

A

An AA will act as a buffer at a pH close to their pKa value

64
Q

How many bonds would there be in a 3 peptid bond?

A

2 bonds between 3 amino acids!

65
Q

Where is the start of a peptide bond and what is its name?

A

It starts at a free amino group which is termed the N-terminal

66
Q

What is at the end of a peptide bond and what is the name of it?

A

Free Carboxyal and the name is C-terminal

67
Q

Can all sulfur containing AAs create disulfide bonds?

A

NO!!! only cysteine can

Cysteine can form bonds with itself

EX: if you have 3 cysteine bonds, how many disulfide bonds can there be?

A: 1.

68
Q

Can cystein bind to more than 1 AA chain?

A

Yes, happens with Insulin where chain A links to chain B and helps with stabilization

69
Q

If you have two peptides; which one would be more soluble at phys pH?

A: pI = 5.2

B: pI= 6.3

A

It would be A, the lower the number means how soluble it would be

pI below pH means + charge (water likes it so it disolves)

pI above pH means - charge

70
Q

What is the clinical importance of changing a drugs pI?

A

If you can increase a pI and bring it closer to the pH of the body it will increase the amount of time the drug lasts (Glargine = long acting insulin)

71
Q

What is the recommended daily allowance of protein for a person?

A

0.36 g of “high quailty” protein per pound

72
Q

What is a glucogenic amino acid?

A

one that gets converted into glucose to be used as fuel in the body

73
Q

What incretins?

A

When a person eats or has glucose in the system they release two peptides Glucagon-like peptide-1 (GLP) and Glucose-dependent insulinotropic peptide (GIP) causes insulin to be released in pancreas

74
Q

What is bad about GLP-1

A

It get broken down by protease - dipeptidyl peptidase-4 (DPP-4) really quickly so you dont get much of an effect

75
Q

Where does DDP-4 cut GLP-1?

A

Will cut after alanine or proline which will cause GLP-1 to be inactive

76
Q

What is exendine-4?

A

A peptide found in gila monster venom, it showed similar biological property of human GLP-1, but was resistant to DPP-4

77
Q

What is Exenatide?

A

Byetta, bydureon. Synthetic Exendine-4

Used to treat type two diabetes and allows for pancrease to release more insulin.

The change to the N-term of GLP-1 allowed it to be longer acting beacuse it was not cut by DDP-4

78
Q

What is the problem with Exenatide?

A

It can lead to an immune reponse within the pancreas and cause inflammation

**still has gila monster amino acids

79
Q

What is liraglutide?

A

Victoza; was created to circumvent the immunogenicity of byetta

Used once daily; and contains an acetylatyed form (Fatty acid), this makes it nonpolor and have hydrophobic effects and the DDP-4 is unable to remove it as eaily allowing for it to be long acting