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SL12100 Health and Disease Y1 > Lecture 7- Introduction to Nucleic acids, nucleotide biosynthesis and catabolism > Flashcards

Lecture 7- Introduction to Nucleic acids, nucleotide biosynthesis and catabolism Flashcards

Introduction to Nucleic acids, nucleotide biosynthesis and catabolism

1
Q

The building blocks of DNA

A

DNA nucleotides

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2
Q

Name the four types of DNA nucleotides

A
  • deoxyadenosine phosphate
    -deoxyguanosine phosphate
  • deoxythymidine phosphate
  • deoxycytidine phosphate
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3
Q

Draw the structure of deoxyadenosine phosphate

A
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4
Q

Draw the structure of deoxyguanosine phosphate

A
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5
Q

Draw the structure of deoxythymidine phosphate

A
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6
Q

Draw the structure of deoxycytidine phosphate

A
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7
Q

Three components of a nucleotide

A
  • phosphate, sugar, base- a ring of nitrogen and carbon atoms
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8
Q

The deoxyribose sugar and phosphate are always the same in DNA nucleotides. What is the variable group?

A

base.

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9
Q

Nucleoside

A

sugar and base

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10
Q

Nucleotide

A

sugar, phosphate and base

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11
Q

Do the deoxyribose sugars in DNA nucleotides exist as beta or alpha anomers?

A

beta

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12
Q

Give the two categories of bases in DNA nucleotides. Which bases fall into these categories?

A
  • adenine and guanine are purines
  • cytosine and thymine are pyrimidines

purines= two rings
pyrimidines= one ring

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13
Q

What is the primary structure of DNA?

A
  • Contains all the genetic information that we need.
  • The information is contained in the sequence of bases in the DNA
  • Primary structure- the sequence of bases held together by the sugar phosphate backbone. The phosphate and ribose sugar bond- this is called a phosphodiester bond.
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14
Q

DNA sequence is read from ‘5 to ‘3. What does this refer to?

A

The carbon atom in the deoxyribose sugar to which the phosphate group bonds.

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15
Q

What is the secondary structure of DNA?

A
  • The secondary structure= Two antiparallel polynucleotide strands coiled around each other to form a double helix.
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16
Q

What causes the two polynucleotide strands to come together to form the secondary structure of DNA? How many hydrogen bonds form between A and T and how many form between C and G?

A
  • complementary base pairing
  • 2 hydrogen bonds form between A and T
  • 3 hydrogen bonds form between C and G- due to three hydrogen bonds the C and G pair bind much more strongly than A and T
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17
Q

The 2 hydrogen bonds between A and T and the three between C and G is important because….

A

the base pairing maintains a constant distance between the sugar-phosphate backbones of the two chains as they coil around each other.

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18
Q

The two strands are antiparallel in DNA double helix. What does this mean?

A

One strand goes from 5’-3- and the other from 3’-5’.

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19
Q

Describe the tertiary structure of DNA.

A
  • The way in which the double helix is packed into the cell.
  • DNA strands wind around chromatin proteins. chromatin is made up of histones with DNA and RNA. This looks like beads on a string.
  • The chromatin fibre is arranged into a type of solenoidal scaffolding which condenses and makes up the chromosomes.
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20
Q

The primary structure of RNA is ……….. to the primary structure of the DNA it was formed from during transcription

A

complementary

21
Q

RNA contains ribose sugars. What is the difference between ribose and deoxyribose sugar? Draw a ribose sugar

A

the ribose sugar contains an OH group rather than an H group

22
Q

In RNA nucleotides which base replaces thymine?

A

uracil

23
Q

DNA is used for long term storage. How is this different to RNA?

A
  • RNA is used only briefly.
  • RNA is typically very unstable because it doesn’t need to hang around for very long.
24
Q

Draw adenosine 5’ phosphate

A
25
Q

Draw Guanosine 5 phosphate

A
26
Q

Draw cytosine 5 phosphate

A
27
Q

Draw uridine 5 phosphate

A
28
Q

Secondary structure of RNA

A
  • Some regions within the single polynucleotide strand interact with themselves through base pairing. The shape of RNA is determined by how the bases interact within the polynucleotide strand
  • Adenine pairs to uracil
  • Guanine pairs to cytosine
29
Q

mRNA

A
  • mRNA= relays the code for a protein from DNA to the protein production site
30
Q

tRNA

A

the adapted unit linking the triplet code on mRNA to specific amino acids

31
Q

rRNA

A

present in ribosomes- the site of protein synthesis. It is important both structurally and catalytically.

32
Q

Describe the central dogma. In what situations would RNA be used to form DNA?

A

DNA stores genetic info. DNA is used to produce RNA which is used to form proteins.
- Some organisms store info as RNA and to infect cells the RNA is reverse transcribed back to DNA (retroviruses)

33
Q

Biosynthesis of nucleic acids…There are two pathways to form nucleic acids. Explain.

A
  • Salvage= used to recreate DNA/RNA by recycling molecules.
  • De Novo= ‘from the beginning’. This pathway makes the nucleotides that form DNA and RNA, from scratch. Small precursors undergo reactions to form ribonucleotides, which can later be converted into deoxyribonucleotides.
34
Q

Outline the key points of purine de novo synthesis. Draw ribose 5 phosphate.

A
  • In purine nucleotides, the base- made up of two nitrogen-containing rings are built on top of the ribose sugar. This is done through a series of multistep reactions.
  • A ribose-5-phosphate is phosphorylated into a PRPP molecule. Two phosphates are added to ribose-5-phosphate from ATP, which is then dephosphorylated into AMP. PRPP synthetase catalyses this reaction.
  • A nucleophilic substitution reaction then converts PRPP into -5-phosphoribosyl-1-amine. The phosphates in PRPP are substituted for an NH2 group. Now that amine has been substituted, the rings can be built in a series of multistep reactions.
  • At the end, we produce inosine 5’ phosphate which is a common precursor which can form both adenosine and guanosine- the two purine ribonucleotides. Formation from a common precursor saves energy and enzymes
    .
35
Q

Where does energy for the reactions in de novo synthesis of purines come from?

A
  • Energy for the reaction comes from the dephosphorylation of ATP to ADP
36
Q

In de novo synthesis of purine how do we get a single carbon in a multistep reaction when one is needed?

A

Where a single carbon addition is required, the C is often provided from a tetrahydrofolate compound and this provides a useful approach to inhibition of synthesis.

37
Q

How does de novo synthesis of pyrimidine nucleotides differ from that of purines?

A

The nucleic acid ring (the base) is built first rather than last and then attached to the ribose ring.

38
Q

There are many stages in the de novo synthesis of pyrimidine nucleotides. One of which is the conversion of monophosphates from triphosphates. State the two step reaction

A
  1. Nucleotide monophosphate (NMP) + ATP -> Nucleotide diphosphate (NDP) + ADP
    The enzyme which catalyses this reaction is a monophosphate kinase- specific for each base but not for the sugar.
  2. NDP + ATP -> NTP + ADP
    The enzyme which catalyses this step is a diphosphate kinase- non-specific.
39
Q

give the example of conversion of nucleotide monophosphate to triphosphate that occurs at the end of de novo synthesis of pyrimidine nucleotides. Hint: it forms the purine nucleotide cytidine triphosphate.

A

UMP/ uridylate is phosphorylated and changed from monophosphate UMP to triphosphate UTP
Uridine triphosphate/UTP is then converted into the purine nucleotide cytidine triphosphate/ CTP

40
Q

How are ribonucleotides converted to deoxyribonucleotides?

A
  • Ribonucleotides have an OH group in their sugar, deoxyribonucleotides do not.
  • The ribonucleotides are reduced to get rid of the OH group and form deoxyribonucleotides.
  • An enzyme- reductase does this reaction. A thiol- SH reducing agent.
    Ribonucleotide + Reductant (SH)2 –> deoxyribonucleotide + Reductant (s-s)
41
Q

What is the difference between uracil and thymine? How do we get from uracil to thymine?

A

thymine has a methyl group added in the nucleotide monophosphate stage. The enzyme which catalyses the reaction is thymidylate synthase.

42
Q

How can pyrimidine nucleotides be broken down?

A

reduction or oxidation

43
Q

Describe reduction of Pyrimidine nucleotides. What is formed

A
  • The ring is reduced to break the bonds within the ring- NADPH is used as a reducing agent and it regenerates as NADP. The ring will open as a result of this reduction.
  • Reductive metabolism of pyrimidines gives small water-soluble metabolites
44
Q

Describe oxidation of pyrimidine nucleotides. What is formed?

A
  • In the oxidative catabolism, oxygen opens up the ring. Products of this catabolism are also small, water-soluble compounds. Any degradation products are readily excreted, as with reduction.
45
Q

In purine nucleotides, how does the catabolism of adenosine differ from guanosine?

A
  • Adenosine- amine is removed and then ribose.
  • Guanosine- the ribose is removed and then the amine.
46
Q

The catabolism of the purine nucleotides leads to the production of….

A

uric acid. Uric acid is large- two rings- and solubility is low. It is secreted into the urine as sodium urate crystals.

47
Q

Effects of abnormal catabolism of purine nucleotides…

A

disease. This is caused from the insolubility of the degradation of the by-product, uric acid. excess accumulation of uric acid causes gout.

48
Q

What is the treatment for gout and how does it work/

A

The treatment for gout is Allopurinol. Allopurinol inhibits xanthine oxidase which oxidises xanthine into uric acid. Therefore, uric acid cannot be formed. Xanthine can then be converted into the soluble hypoxanthine instead.

SL12100 Health and Disease Y1 (18 decks)

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