Nutrition And Antibiotics Flashcards
(82 cards)
1
Q
Where does a vitamin deficiency show up first?
A
In rapidly growing tissues and nervous tissues due to their high energy demands.
2
Q
What 2 vitamins are water soluble?
A
Vitamin B and Vitamin C
3
Q
What 4 Vitamins are lipid soluble?
A
Vitamin A, Vitamin D, Vitamin K, Vitamin E
4
Q
Are water soluble vitamins highly variable in their structures?
A
yes
5
Q
Are water soluble vitamins highly variable in their functions?
A
no
6
Q
What is the main functions of water soluble vitamins?
A
To carry mobile metabolic groups as either activated carriers or co enzymes
7
Q
What do all water soluble vitamins except vitamin C require?
A
Modifications for their functions e.g chemical changes. They are precursor molecules
8
Q
Are water soluble vitamins readily excreted and degraded?
A
yes
9
Q
Are lipid soluble vitamins highly variable in their structures?
A
No they are all isoprenoid compounds that are structurally similar
10
Q
Are lipid soluble vitamins highly variable in their functions?
A
Yes, they are functionally diverse and are generally not activated carriers or co enzymes
11
Q
What is the main functions of lipid soluble vitamins?
A
Act like hormones (Vit A, Vit D) and signalling molecules that are toxic in excess
12
Q
Are lipid soluble vitamins readily absorbed and extracted from food?
A
No
13
Q
What is the group carried and what is the vitamin precursor for NADH and NADPH?
A
group carried is e- and they come from the precursor nicotinate (B3)
14
Q
What is the group carried and what is the vitamin precursor for FADH2?
A
group carried is e- and they come from the precursor riboflavin (B2)
15
Q
What is the group carried and what is the vitamin precursor for co enzyme A?
A
It carries an acyl group and comes from the precursor pantothenate (B5)
16
Q
What is the group carried and what is the vitamin precursor for tetrafolate?
A
Carries 1 carbon units and comes from folate (B9)
17
Q
What is the result of a deficiency in vitamin B2 - riboflavin?
A
Cheliosis and angular stomatisis (lesions of the mouth), dermatitis
18
Q
What is the result of a deficiency in vitamin B3 - nicotinic acid?
A
Pellagra, dermatitis, depression, diarrhea
19
Q
What is the result of a deficiency in vitamin B9 - folic acid?
A
Anemia, neural tube defects in development
20
Q
What is the function of Vit C?
A
antioxidant/reducing agent that acts as an electron donor and accelerates hydroxylation
21
Q
What is the result of a deficiency in vitamin C?
A
scurvy - swollen and bleeding gums, subdermal hemorrhaging
22
Q
What does Vit D do?
A
regulates calcium and phosphate metabolism.
23
Q
What is the result of a deficiency in vitamin D?
A
Rickets (children) - skeletal deformities and impaired growth. Called osteomalacia in adults - soft bending bones
24
Q
Ascorbate is the ionised form of?
A
ascorbic acid
25
Dehydroascorbate acid is the oxidised form of?
ascorbate
26
Why can humans not synthesise Vit C?
Human cells cannot perform the last step of Vit C synthesis, the conversion of L-guluno-y-lactone into ascorbic acid which is catalysed by the enzyme gulonolactone oxidase. The gene that codes for the enzyme is actually present in the human genome but it is not functional due to the accumulation of mutations that turned it into a non-functional pseudogene.
27
What are some advantages that may result from human snot being able to synthesise their own Vit C?
1. The reaction of L-gulono-y-lactone also produces H2O2, a reactive oxygen species
2. Pseudogenes have a role in controlling gene expression
3. Vit C regulates a key stress inducing transcription factor (hypoxiainduciblefactor-1-a) so the lack of Vit C synthesis allows fine tuning of the stress response system based on nutritional status
28
How does Vit C aid in wound healing?
I helps make collagen which then goes on to make scar tissue to close the wound
29
Describe the structure of collagen:
Amino acid sequence of a part of a collagen chain:
- every 3rd residue is a glycine
- proline and hydroxyproline are abundant (a common tripeptide is glycine-proline-hydroxyproline)
- extracellular collagen contains 3 helical peptide chains (1000 residues long)
- stabilisation of the collagen triple helix requires hydroxyproline
30
What is the enzyme that turns proline into hydroxyproline?
Proline hydroxylase
31
What else happens when proline forms hydroxyproline?
Vitamin C (ascorbic acid) and Fe3+and Co2 make dehydroxy ascorbate and Fe+ and O2. Then 2-oxogluterate and O2 and Fe2+ along with proline make succinate + Fe3+ and CO2 and hydroxyproline
32
What is meagoblastomic anemia?
When cells cannot produce DNA quickly enough to divide at the correct time so cells grow too large before division.
33
What is the cause of megoblastomic anemia?
Lack of vitamin B9 - folate which is required for DNA synthesis
34
What can prevent and cure megoblastomic anemia?
Wills factor - a nutritional factor in yeast
35
What do folate/tetrahydrofolate derivatives exist as?
Polyglutamates
36
Where are folate/tetrahydrofolate derivatives converted into a monogluatmate/active form and how does it happen?
In the intestine and can be absorbed by active transport. Folate goes to tetrahydrfolate which is the active form and it requires 2 2 reactions that are both catalysed by dihydrofolate reductase. Also requires NADPH as the electron donor. Folate - dihydrofolate - tetrahydrofolate
37
Where are folate/tetrahydrofolate derivatives stored and why?
Stored in the liver as polyglutamates by the addition of more glutamic acid residues which results in liver cells to yeild a poly-y-tail. By storing tetrahydrofolate inside the liver it helps to retain THF inside cells and bind more tightly to enzymes
38
What is the structure of folic acid/folates?
A bicyclic, heterocyclic, pteridine ring
P-amino benzoic acid
Gluctamic acid
39
What is an antimetabolite?
A synthetic compound, usually structurally similar to the metabolite that interferes with the metabolite to which it is related
40
What is an inhibitor of bacterial dihydrofolate reductase?
Methotrixate as it has a 100 fold higher affinity than to substrate
41
What are things that block growth i.e inhibit dehydrofolate synthesis?
Sulfanimides
42
How are neural tube defects caused?
By genetic predisposition or environmental influences
43
Describe the most common cranial neural tube defect?
Anencephaly
- the cerebral cortex fails to develop
- accounts for 1/3 of all NTD’s
- lethal
44
What is the most common caudal NTD?
Spina bifida
- the spinal chord develops abnormally
- accounts for 2/3 NTD
- causes paralysis of lower extremities and impaired bladder + bowel function, not usually fatal unless accompanied by other conditions
45
What is the methylation hypothesis?
It is proposed that folate prevents NTD by increasing methylation of various molecules that are essential for cellular processes
46
What is an antimetabolite that is an anticancer drug that inhibits dihydrofolate reductase in humans?
Aminopterin
47
What is an antibiotic?
A medicine that inhibits the growth of or destroys micro organisms
48
What are bacteriostatic antibiotics and an example?
They block growth and e.g tetracyclines and sulphonamides
49
What are bactericidal antibiotics and give an example:
They kill the bacteria e.g penicillin
50
Who first discovered penicillin?
Ernst Duchesne in 1896, a French medical student
51
When did Alexander Flemming discover penicillin and how?
1928, along with frank diggins and almorth wright. A fungal spore is through to have drifted up from allergist John Freemans lab a floor below. Subsequent research by Lord Florey and a german biochemist Ernst chain revealed that the mould juice (penicillin) could be used as a chemotherapeutic agent
52
What was the method used to see if penicillin was successful?
Peritoneal injection of bacterial suspension then injected peniillin 1 day later. 8 hurly injections of penicillin and for 36 hours mice were sick (some died). As time progressed, health improved. Then 3-4 days later the infected mice were undistinguishable from healthy mice
53
How did penicillin help in WWII?
Highly beneficial for the treatment of wound pathogens such as stapholoccocus
54
Following WWII, what was penicillin used for?
Rheumatic fever and syphillis
55
How does penicillin and blue cheese relate?
They play a central role in the production of blue cheese and various meat products
56
What are the 5 mechanisms of antibiotic action?
1. Inhibition of cell wall synthesis
2. Inhibition of protein synthesis
3. Inhibition of DNA/RNA synthesis
4. Inhibition of folate synthesis
5. Membrane disruption
57
What is the mechanism of penicillin?
Inhibition of cell wall synthesis
58
Describe the mechanism of antibiotics: inhibition of cell wall synthesis
Peptidoglycan is a component of bacterial cell walls.it is a structural macromolecule with a net like composition to provide rigidity and support to the outer cell wall. Peptidoglycan is a polymer of a short chain amino acid peptide portion and a carbohydrate portion, the glycan. In order to form the cell wall, a single peptidoglycan chain cross links to other peptidoglycan chains through the action of the enzyme PP transpepsidase (penicillin binding protein)
59
Describe the mechanism of antibiotics: inhibition of protein synthesis
Aminoglycosides bind to the bacterial ribosomal RNA, disrupt ribosomal structure leading to mistranslated proteins that can missfold resulting in cell death.
60
Describe the mechanism of antibiotics: inhibition of DNA/RNA synthesis
Done by rifamyosin which binds to actively transcribing RNA polymerase enzyme and blocks synthesis
61
Describe the mechanism of antibiotics: inhibtion of folate synthesis
Done by sulfanaminde drugs which inhibit dihydroteroate synthase that forms folic acid
62
Describe the mechanism of antibiotics: membrane disruption
Lipopeptide antibiotics e.g doptomyocin which is a peptide sequence which a fatty acid moiety is covalently attached. Membrane disruption by loss of membrane potential
63
What are SNAPP’s?
Structurally nanoengineered antimicrobial peptide polymers. It is a polymer that can rip apart cell walls by interacting with the peptidoglycans
64
What are the 3 classes on antibiotic resistance pathogens that are major threats to human health?
1. MRSA - methocillin resistance stapholococcus 80% of staph are resistant to penicillin and 1900 deaths per year
2. Drug resistant gram -ve bacteria - klebsiella pneumoniae
3. Drug resistant myobacterium tuberculosis - leading cause of death
65
How many antibiotics get prescribed to humans and food animals?
Humans - 1.4million kg
| Food animals - 14 million kg
66
What are the 2 types of resistances to antibiotics?
1. Inherent
| 2. Aquired
67
Describe inherent resistance:
Inaccessibility of antibiotic genes found in bacterial chromosomes
68
Describe acquired resistance:
Bacteria that was previously suceptible to some form of antibiotic but then developed resistance. Resistance can be developedin a subpopulation of strands of bacteria or it can be across complete strands
69
What are the 2 types of acquired bacterial resistance to antibiotics?
1. Vertical gene transfer
| 2. Horizontal gene transfer
70
Describe vertical gene transfer:
The transfer of spontaneous resistance gene mutations in the bacterial chromosomes to bacterial progeny during DNA replication. Although spontaneous mutations are rare, bacteria grow so fast and divide so fast that it doesn’t take long for resistance to develop
71
Describe horizontal gene transfer:
Genetic material contained in small packets of DNA can be transferred between individual bacteria of the same species or even between different species
72
What are the 3 mechanisms of horizontal gene transfer?
1. Conjugation
2. Transformation
3. Transduction
73
Describe the method of horizontal gene transfer: conjugation
The main mechanism. Transmission of resistance genes following direct contact between 2 bacteria via pilus. Plasmids are located in the cytoplasm of the donor and recipient cell and exchange through the pilus.
74
Describe the method of horizontal gene transfer: transduction
Antibiotic resistance gene is transferred between 2 closely related bacteria by means of bacteriospecific viruses (bacteriophages).
75
Describe the method of horizontal gene transfer: transformation
Occurs when naked DNA is released into the external environment normally due to death and cell lysis of an organism and is taken up by a another bacterium. The antibiotic resistance gene can be integrated into the chromosome or plasmid of the recipient cell.
76
What are the 3 mechanisms for bacteria to get rid of an antibiotic?
1. Efflux pump
2. Destroy the antibiotic
3. Modify + inactivate antibiotic
77
Describe the mechanism for bacteria to get rid of an antibiotic: efflux pump
For antibiotics to be effective, they must reach their bacterial targets and act in some reasonable time frame. The pumps are variants of membrane pumps to move molecules in and out of cells.
78
Describe the mechanism for bacteria to get rid of an antibiotic: destroy antibiotics
An example is the hydrolytic deactivation of the B lactam ring in penicillin by the expression of the enzyme B lactamase or penicillinase by resistant bacteria. Lactamase producing bacteria secrete their enzyme into the periplasm to destroy the antibiotics before they reach their targets. Methacillin is however resistant to B lactamase
79
Describe the mechanism for bacteria to get rid of an antibiotic: modify and deactivate the antibiotic
The antibiotic chloamphenicol can be enzymatically inactivated by the addition of an acetyl group or phosphate group. These modifications decorate the periphery of the antibiotic and interrupt the binding to ribosomes
80
How does MRSA work?
It releases fatty decoys to avoid and trick antibiotics (Daptomyacin can be used as treatment but is not so successful)
81
When developing new antibiotics what are the 3 steps that should be taken?
1. Modification of the common core structures of different antibiotic classes using medicinal chemistry
2. Identification of new antibiotic scaffolds through searches of unexplored ecological niches and bacterial taxa
3. Bioinformatic analysis of bacterial genomes
82
When were sulfa drugs and B lactams discovered
1940- In the golden age of discovery
| Golden age of medicinal chem was 1995-2001
