Lecture 49

Question 1

_____ must be synthesized from Uracil in cells undergoing DNA synth/replication.

Answer 1

THYMINE

Question 2

The biosynthesis of Purines begins with the ribose component of nucleosides/tides which comes from the ____ ____ ____ (PPP.) ____-6-P (from glycolysis) is converted to 6-phosphogluconolactone via the enzyme ____-6-P _____ (which requires _____ as a cofactor), and in two more steps the ribose-5-P is formed.

Answer 2

PENTOSE PHOSPHATE PATHWAY.

G-6-P is converted

G-6-P DEHYDROGENASE

NADP

Question 3

One of the rate limiting steps in purine synthesis involves the conversion of R-5-P to ______ via the enzyme Ribose Phosphate pyrophospho-kinase and ATP. This step can be feedback inhibited by ___, ___, and ____.

Answer 3

PRPP

IMP, AMP, and GMP.

Question 4

The major regulatory step in Purine biosynth involves the conversion of PRPP to 5-_________ via the enzyme Amidophosphoribosyl transferase, using ______ (converted to ______ )as an amino source.

Answer 4

PRPP

5-PHOSPHORIBOSYLAMINE

GLUTAMINE

GLUTAMATE

Question 5

Amidophosphoribosyl transferase is feedback inhibited by ____, ____, and ____ (the monophosphate versions of the particular purines that are made in the reaction.)

Answer 5

AMP, IMP, and GMP.

Question 6

The AAs involved in purine biosynth are: 2 _____, one _____, and one Apartate, with 2 C units contributed by _____ (single C unit carrier.)

Answer 6

AAs involved in Purine biosynth are: 2 GLUTAMINES, one GLYCINE, and one ASPARTATE, with 2 C units contributed by THF.

Question 7

____ is the nucleotide precursor for both AMP and GMP, with _____ as its base.

Answer 7

IMP is the precursor with HYPOXANTHINE as its base.

Question 8

______ Acid is a drug used to prevent graft rejection. It acts as a ______ uncompetitive inhibitor of IMP dehydrogenase, depriving T- and B-cells of GMP.

Answer 8

MYCOPHENOLIC acid is a drug used to prevent graft rejection. It acts as a REVERSIBLE uncompetitive inhibitor of IMP DH.

Question 9

Gout is characterized by buildup up _____ acid above 9 mg/dL in serum. Remember that _____ is the final breakdown product of purines via the enzyme _____ oxidase. Allopurinol acts as a ____ inhibitor of _____ oxidase, so less Uric acid is produced

Answer 9

Uric acid

Urate

Xanthine oxidase

Competitive inhibitor

Xanthine oxidase

Question 10

____ ___ syndrome is characterized by a(n) ______ recessive mutation leading to a complete lack of _____ and severe hyperuricemia. These patients tend to self-inflict harm (i.e. biting lips.)

Answer 10

Lesh Nyhan syndrom is characterized by an AUTOSOMAL recessive mutation leading to a complete lack of HGPRT.

Question 11

____ acid is the common intermediate for Pyrimidine synthesis.

Answer 11

Orotic acid

Question 12

The first step in the pyrimidine pathway creates the same product as in the first step of the urea cycle: ______ phosphate. However, this occurs in the _____ of the cell for pyrimidine synthesis, which is not where it occurs in the urea cycle. Also remember the precursors for this first product in the urea cycle were ammonia, bicarb, and ATP, but in pyrimidine synth _____ is used instead of ammonia.

Answer 12

Carbamoyl phosphate

Cytosol

Glutamine

Question 13

Carbamoyl Phosphate synthetase is inhibited by _____ and activated by _____ and _____.

Answer 13

It is inhibited by UTP, and activated by ATP and PRPP.

Question 14

Pyrimidine synthesis differs from Purine synthesis in that Pyrimidine synth begins with _____ formation followed by link to _____. This is opposite in Purine synth.

Answer 14

Pyrimidine synthesis begins with RING formation followed by link to RIBOSE.

Question 15

CAD, the first enzyme complex involved in pyrimidine synthesis, is a single polypeptide with 3 domains, each with a different catalytic activity, including ______ ______ ______ (C), ______ ______(A), and ______ (D)

Answer 15

Including Carbamoyl Phosphate Synthetase, Aspartate Transcarbamylase, and Dihydroorotase.

Question 16

The second enzyme complex involved in pyrimidine synth is _____ synthase, which is composed of orotate phosphoribosyl transferase that adds _____ to Orotate forming OMP and then OMP decarboxylase forming ____ from OMP.

Answer 16

UMP-synthase

PRPP

UMP from OMP.

Question 17

Low UMP synthase activity (in either one of the 2 enzyme components) leads to _____ aciduria, showing symptoms such as _____ anemia and abnormal growth. It can be treated with a _____-rich diet.

Answer 17

OROTIC aciduria

MEGALOBLASTIC anemia

URIDINE-rich diet.

Question 18

____ is the AA that is unique to purine synthesis; both Glutamine and Apartate are shared.

Answer 18

Glycine

Question 19

____ synthetase forms Cytosine from Uracil (UTP) and requires _____ and Glutamine.

Answer 19

CTP synthase forms Cytosine from Uracil and requires ATP and Glutamine.

Question 20

______ ______ and ______ ______ are the 2 enzymes required to convert RNA to DNA.

Answer 20

THYMIDYLATE SYNTHETASE

RIBONUCLEOTIDE REDUCTASE

Question 21

_____ is a general inhibitor of Ribonucleotide reductase and _____ is a general activator.

Answer 21

dATP is a general inhibitor, and ATP is a general activator.

Question 22

Before being converted to dTTP, dUDP is first converted to _____, which then gains a Carbon unit from ____ to form _____, which is then phosphorylated to dTTP.

Answer 22

dUTP is first converted to dUMP, which then gains a Carbon unit from THF to form dTMP, which is then phosphorylated to form dTTP.

Question 23

______ synthase coverts dUMP to dTMP using THF, (which is oxidized to form DHF) for the one Carbon unit.

Answer 23

THYMIDYLATE synthase

Question 24

5-FU and Methotrexate are used as chemotherapies by inhibiting ______ synthase, so no dTMP for rapidly dividing cancer cells.

Answer 24

They inhibit THYMIDYLATE synthase.