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Biochemistry Exam 3 > Chapter 32: Nucleotide Metabolism > Flashcards

Chapter 32: Nucleotide Metabolism Flashcards

1
Q
  1. Nucleotides make up
A

nucleic acids (DNA/RNA)

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2
Q

How do we get nucleotides?

A

They are nonessential nutrients - can be synthesized in the body.

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3
Q

Process of getting nucleoproteins in food.

A
  1. digested in stomach by gastric acid and pepsin to protein and nucleotides
  2. further broken down in small intestine by endonucleases to nucleotides
  3. absorbed/degraded by nucleotidases to base, pentose, phosphate
  4. base degraded/reused, pentose reused
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4
Q

Two types of bases and the difference between them

A

Purines and Pyrimidines:
Purines (A, G) have 2 rings
Pyrimidines (C, T, U) have 1

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5
Q

Structure of adenine

A

I don’t know how to add pictures!

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6
Q

Structure of guanine

A

TO BE ADDED

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7
Q

Structure of cytosine

A

TO BE ADDED

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8
Q

Structure of uracil

A

TO BE ADDED

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9
Q

Structure of thymine

A

TO BE ADDED

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10
Q

What is the difference between ribose and deoxyribose?

A

Ribose- found in RNA, has OH group on carbon 2

Deoxyribose- found in DNA, has H group on carbon 2

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11
Q

What makes up a nucleotide?

A

Sugar, base, and phosphate

vs nucleoside made up of base and sugar

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12
Q

What is PRPP and how is it made?

A

An activate ribose made from ribose-5-phosphate. Enzyme PRPP synthetase makes it.
AKA 5-phosphoribosyl-1-pyrophosphate. (phosphate at position 5, pyrophosphate at position 1)

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13
Q

Where does ribose-5-phosphate come from?

A

the pentose phosphate pathway OR from ribulose with the enzyme ribokinase

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14
Q

What are the two synthesis pathways for nucleotides?

A
  1. de novo (from bits and parts)- more energy, longer

2. salvage (recycle from pre-existing nucleotides)

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15
Q

De novo pyrimidine synthesis overview

A

pyrimidine ring synthesized from bicarbonate, aspartate, glutamine

  1. bicarbonate + NH4 from glutamine -> carbamoyl phosphate= 2 ATP, carbamoyl phosphate synthetase II
  2. carbamoyl phosphate + aspartate -> pyrimidine ring
  3. pyrimidine ring activation w/ PRPP
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16
Q

De novo pyrimidine synthesis specifics- making carbamoyl phosphate

A
  1. bicarbonate + ATP -> carboxyphosphate
  2. carboxyphosphate + NH3 from Gln -> carbamic acid
  3. carbamic acid + ATP -> carbamoyl phosphate
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17
Q

De novo pyrimidine synthesis specifics- attachment to ribose sugar (through orotate)

A
  1. carbomoyl phosphate + aspartate -> carbamoylaspartate (enzyme= aspartate transcarbamoylase)
  2. carbomoylaspartate + H -> Dihydroorotate (ring)
  3. dihydroorotate + NAD+ -> orotate
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18
Q

De novo pyrimidine synthesis specifics- attachment to ribose sugar (orotate to UMP)

A
  1. orotate + PRPP -> oretidylate
  2. oretidylate + H -> uridylate (enzyme= orotidylate decarboxylase)
  3. uridylate -> UMP
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19
Q

De novo pyrimidine synthesis specifics- attachment to ribose sugar (UMP to end)

A
  1. UMP -> UDP (UMP kinase, ATP used)
  2. UDP -> UTP (nucleoside diphosphate kinases)
  3. UTP -> CTP (replace carbonyl group w/ amino group from glutamine, ATP used)
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20
Q

Conversion of UMP into other pyrimidines

A

Change UMP to dUMP, then change dUMP to dTMP through methylation using thymidylate synthase

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21
Q

De novo pyrimidine biosynthesis regulated by ____.

A

feedback inhibition- lots of UTP will prevent committed step (bicarbonate + NH4)

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22
Q

What is orotic aciduria?

A

Disease associated with defect in pyrimidine synthesis- it is hereditary, on chromosome III (UMP deficiency)
Causes loss of functional UMP synthetase.
Effects: no UMP, excess orotate, severe anemia, growth retardation
Treatment: feeding w/ UMP (changed to UTP which stops pathway by feedback inhibition)

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23
Q

Pyrimidine nucleotide degradation

A

Pyrimidine rings can be fully degraded to soluble structures (vs purines which make uric acid)

24
Q

What are the sources of carbons and nitrogens in purine rings?

A

Aspartate gives 1 N; Glycine gives 1 N and 2 C; Glutamine gives 1 N; CO2 gives 1 C; N10-formyl-THF gives 2 C

25
Q

What molecule donates the ribose onto which purine nucleotides are assembled?

A

PPRP

26
Q

How are the key steps in purine nucleotide biosynthesis regulated?

A

Feedback inhibition

27
Q

How are AMP and GMP made from IMP?

A

IMP -> XMP with IMP dehydrogenase, XMP -> GMP with GMP synthetase (also needs ATP)
IMP -> adenylosuccinate with Adenylosuccinate synthetase (needs GTP), adenylosuccinate -> AMP with adenylosuccinate lyase

28
Q

Why is the salvage pathway for purine nucleotides important?

A

Useful b/c of high energy cost for de-novo synthesis of nitrogen bases
Important in some organs that lack enzymes required for de-novo synthesis pathway so they depend on exogenous source of purines
-ex: brain has low level of PRPP glutamyl amidotransferase
-erythrocytes/leukocytes can’t synthesize 5-phosphoribosylamine

29
Q

What enzymes add PRPP to bases to form nucleotides?

A

Phosphoribosyltransferases

30
Q

How do you make IMP, GMP, AMP from the salvage pathway for purine nucleotides?

A

Hypoxanthine or guanine + PRPP -> IMP or GMP with hypoxanthine-guanosyl-phosphoribosyl transferase (HGPRT)
Adenine + PRPP -> AMP with adenine-phosphoribosyl transferase (APRT)

31
Q

Lesch-Nyhan Syndrome

A

Accumulation of guanine/hypoxanithine due to absence of HGPRT, X-linked (only affects males), high presence of guanine and hypoxanthine
Effects: overproduction of uric acid, neurologic disability, behavioral problems

32
Q

What do the major pathways of purine nucleotide catabolism lead to?

A

Uric acid

33
Q

AMP to Uric Acid pathway

A

AMP -> IMP (AMP deaminase)
-> Inosine (nucleolidases)
-> hypoxanthine (purine nucleoside phosphoylase)
-> uric acid (xanthine oxidase)
ALSO AMP -> Adenosine (nucleotidases)
Adenosine -> Inosine (adenosine deaminase)

34
Q

Severe combined immuno-deficiency (SCID)

A

Genetic defect in the gene that codes for AMP deaminase leasing to excess dATP.
1st disease to be cured with gene therapy (injection with purified AMP deaminase)

35
Q

XMP to Uric Acid pathway

A

XMP -> Xanthosine (nucleotidase)
Xanthosine -> Xanthine (purine nucleoside phosphorylase)
Xanthine -> uric acid (xanthine oxidase)

36
Q

GMP to Uric Acid pathway

A

GMP -> Guanosine (nucleotidase)
Guanosine ->Guanine (purine nucleoside phosphorylase)
Guanine -> Xanthine (guanine deaminase)
Xanthine -> uric acid (xanthine oxidase)

37
Q

What is gout?

A

Inborn errors leading to overproduction of uric acid (overactive e novo synthesis pathway)
Leads to deposits of uric acid in joints
Causes acute arthritic joint inflammation.
Treatment: give allopurinal which competes with xanthine for xanthine oxidase (less uric acid made)

38
Q

Diseases attributed to reakdown of purine metabolism.

A
  1. lesch-nyhan syndrome= accumulation of guanine/ hypoxanthine absence of HGPRT
  2. SCID= excess dATP due to defect in AMP deaminase
  3. Gout= excess uric acid due to failure of xanthine oxidase
39
Q

What is the 1st purine nucleotide? How does it change into ATP/GTP?

A

IMP
IMP -> AMP ; AMP -> ADP (AMP kinase) ; ADP -> ATP (nucleoside diphosphate kinase)
IMP -> GMP ; GMP -> GDP (GMP kinase) ; GDP -> GTP (nucleoside diphosphate kinase)

40
Q

what is the 1st pyrimidine nucleotide? How does it change into UTP?

A

OMP

OMP -> UMP ; UMP -> UDP (UMP kinase) ; UDP -> UTP (nucleoside diphosphate kinase)

41
Q

Deoxyribonucleotides are synthesized from ________.

A

ribonucleoside diphosphates

Uses NADPH and enzyme ribonucleotide reductase

42
Q

Nucleotide triphosphates are

A

the energy currency

43
Q

Nucleotides are activated intermediates in

A

biosynthesis (UDP-glucose, SAM)

44
Q

Many metabolic pathways are regulated by…

A

by nucleotide levels (cAMP regulation of glucose release)

45
Q

Defects in these metabolic pathways result in diseases such as…

A

SCID, Gout, Lesch-Nyhan Syndrome

46
Q 
The bases in DNA are:
A.	Uracil, adenine, guanine and thymine
B.	Adenine, guanine, cytosine and thymine
C.	Adenine, uracil, cytosine and thymine
D.	Adenine, cytosine, uracil and guanine
A

Adenine, guanine, cytosine and thymine

47
Q

Which element is found in both nucleic acids and proteins?

A

Nitrogen

48
Q

Both the salvage and de novo synthesis pathways of purine and pyrimidine biosynthesis lead to the production of nucleoside-5’-phosphates through the utilization of an activated sugar. The activated sugar intermediate used for this purpose is:

A

Ribose 5-phosphate

49
Q

Gout is characterized by elevated uric acid concentrations in blood and urine due to a variety of metabolic abnormalities that lead to the overproduction of purine nucleotides. Allopurinol is used in the treatment of gout because this drug is an inhibitor of:

A

Xanthine oxidase

50
Q

Hereditary Orotic aciduria is characterized by severe anemia, growth retardation, and high levels of orotic acid excretion. It is produced by deficit of enzymes related with:

A

synthesis of pyrimidine nucleotides

51
Q 
Which is not used in synthesis of a purine ring?
	A.  Glutamine
	B.  Aspartate
	C.  Glycine 
	D.  THF
	E.   Leucine
A

Leucine

52
Q 
Gout is an inflammatory reaction due to uric acid crystallization in soft tissues and joints. One defect of this is in which enzyme of the purine biosynthesis pathway?
	A.   Adenylosuccinase
        B.   Formyltransferase
	C.   IMP cyclohydrolase
	D.   PRPP glutamyl amidotransferase
	E.   PRPP synthetase
A

PRPP synthetase

53
Q 
Hyperuricemia in Lesch-Nyhan syndrome is due to a defect in what pathway?
	A.   Purine biosynthesis
	B.   Pyrimidine biosynthesis
        C.   Purine salvage
	D.   Pyrimidine salvage
	E.   All of the above
A

Purine Salvage

54
Q 
A 4 year old girl presents in the clinic with megaloblastic anemia and failure to thrive. Blood chemistry shows orotic aciduria. Enzyme measurements of white blood cells reveal a deficiency of the pyrimidine biosynthesis enzyme orotate phosphoribosyltransferase and abnormally high activity of the enzyme aspartate transcarbamoylase. Which of the following treatment would reverse the symptoms if carried out chronically? 
	A.   blood transfusion
	B.   white blood cell transfusion
	C.   oral supplement of PRPP
	D.   oral thymidine
	E.   oral uridine
A

Oral uridine

55
Q

Nitrogenous bases are either purines or pyrimidines. The pyrimidines are ,_____, and _____.

	A. adenine, guanine and uracil
	B. adenine, guanine and thymine
	C. cytosine, uracil and thymine
	D. uracil, guanine and thymine
	E. adenine, guanine and cytosine
A

Cytosine, uracil and thymine

56
Q 
Orotic aciduria is an inherited metabolic disease in which orotic acid (orotate) accumulates in the tissues, blood, and urine. The metabolic pathway in which the enzyme defect occurs is:
	A. purine breakdown. 
	B. purine synthesis. 
	C. pyrimidine breakdown. 
	D. pyrimidine synthesis. 
	E. None of the above are correct
A

Pyrimidine synthesis

Biochemistry Exam 3 (10 decks)

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