Metabolism 2 (part 2) Flashcards Preview

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Flashcards in Metabolism 2 (part 2) Deck (194):
1

If the carbon skeleton of an amino acid, after losing its amino group is degraded into acetyl CoA, oxaloacetate, and/or ketone bodies, what is it called?

Ketogenic

(ketone bodies for ketogenesis)

2

What are the 2 ketogenic amino acids?

LL

Lysine and Leucine

3

How many essential amino acids are there?
What does it mean to be essential?

10 out of 20

we can't synthesize essentials

4

How many non-essential AA's are there?
Is arginine essential?

10

Arginine sometimes considered essential, because we don't synthesize enough

5

Is tyrosine an essential AA?

No, it's considered non-essential because we make it from phenylalanine.

However, phenylalanine IS essential

6

What is tyrosine for an individual incapable of metabolizing phenylalanine?

Conditionally essential

7

Name the non-essential AA's

PVT TIM HLL

8

What is the term to define an amino acid losing its amino group, and the leftover carbon skeleton entering GNG pathway?

Glutogenic

9

What is gastric acid and from where is it secreted?

What is its function?

HCl
secreted from parietal cells in the stomach

denatures proteins (begins process) and releases intrinsic factor so B12 can be absorbed

10

What type of hormone is Cholecystokinin?
What is its function?

Peptide hormone

digests Fat AND Protein, stimulates gall bladder, slows gastric emptying, satiety signal

11

What zymogen stimulates the release of a basic solution from the pancreas?
How long is the zymogen and active form?

Secretin

121AA cut to 27 AA hormonal active form

12

What enzyme cleaves trypsinogen to become trypsin?

Enteropeptidase

13

How is trypsin activated?
What does it do?

Trypsinogen > (Enteropeptidase) > Trypsin

Trypsin cleaves chymotrypsinogen > chymotrypsin

14

What are the 3 main zymogens in protein digestion?

Pepsinogen
Chymotrypsinogen
Trypsinogen

15

What zymogen is released by chief cells in the stomach in response to HCl?

Pepsinogen
HCl activates Pepsin

16

Where is chymotrypsinogen made and what does its active form break down?

Pancreas

Chymotrypsin breaks down aromatic AA residues

17

What activates trypsinogen (trypsin)?
What does trypsin activate?

Enteropeptidase

Chymotrypsin (from chymotrypsinogen)
Elastase (from proelastase)
Carboxypeptidase (from procarboxypeptidase)
Lipase (from prolipase)

18

What do trypsin, chymotrypsin, and elastase preferentially cleave?

trypsin - arg/lys residues
chymotrypsin - aromatic AA residues
elastase - hydrophobic AA's

19

After proteins are sufficiently broken down in the lumen how do they get into the enterocyte?

Secondary Active Transport (specific carrier-mediated)

20

What size are the AA chains that enter the enterocyte from the lumen?

Free AA, di, and tri-peptides

(1-3)

21

What catalyzes the cleavage of AA's from the N-terminus of oligopeptides entering the enterocyte?

Aminopeptidase

22

Once 1-3 AA chains are in the enterocyte, what occurs before they are released into the blood?
How are they released into the blood?

Peptidases continue to break into single AA's

Facilitated transport

23

What determines the lifespan of a protein?

The AA at the N-terminus

24

What determines the shelf life of a protein?

PEST sequences (Proline, Glutamate, Serine, Threonine)

(AA sequences that serve as marker for death - more protein has shorter its life)

25

What death marker attaches to Lysine?

Ubiquitin?

26

What structure does the ubiquitin-attached protein enter for degradation?
What survives?

26S Proteasome

Ubiquitin survives the shredder

27

What catalyzes the transfer of amino groups from AA's to Alpha-ketoglutarate?
What is the major co-enzyme in this rxn?

Aminotransferases

Pyridoxal Phosphate

28

What catalyzes the transfer of an amino group of Alanine to Alpha-ketoglutarate to form pyruvate and glutamate?
Alanine > Pyruvate
A-ketoglutarate > Glutamate

Alanine Aminotransferase (ALT)

THE RULE

remember: co-enzyme is pyridoxal phosphate

29

Glutamate > Alpha-Ketoglutarate
Oxaloacetate > Aspartate

amino goes from glutamate to aspartate. What is this called?
What is the co-enzyme?

Aspartate aminotransferase

Pyridoxal phosphate

30

What are 3 important reactants and products of aminotransferase (deamination)?

Glutamate > Alpha-Ketoglutarate
Alanine > Pyruvate
Aspartate > oxaloacetate

31

What AA spontaneously goes through oxidative deamination?
Where does this occur?
What enzyme is involved?
What does this produce?
Why are ATP and GTP allosteric inhibitors of this rxn?

Glutamate
Liver (mitochondria)
Glutamate dehydrogenase
free ammonia (and alpha-keto acid)
NADH is produced (AMP activates)

32

What is the key controlling regulatory step in the urea cycle?
What allosterically regulates?
What is the product?
Where does the amino group come from?

CPSI (Carbamoyl Phosphate Synthetase I)

N-acetylglutamate (high concentrations after eating)

Carbamoyl Phosphate

ammonia comes from Glutamate

33

Where in the body does the urea cycle occur?
Where in the cell?

Liver (principally)

2 rxns in mitochondria (including key CPSI/Carbamoyl-P/N-acetylglutamate rxn)
rest in cytosol

34

Where does the Nitrogen in urea come from?
How many ATP are required to form urea?

Glutamate and Aspartate

4

35

What is the benign way we transport ammonia in blood?

via Alanine and Glutamine

36

What is a product of the urea cycle, an intermediate in the CAC, and can make aspartate in an aminotranferase (transamination) reaction with oxaloacetate?

also a link to GNG

Fumarate

37

What does glutaminase do?

Glutamine > Glutamate

in the liver

38

What happens if the glutamate dehydrogenase reaction is pushed too far toward the formation of glutamate?

It depletes Alpha-Ketoglutarate, which is essential for the CAC to run

(remember Alpha-ketoglutarate + NH3 = glutamate)

this is ammonia toxicity

39

What are the 2 kinds of hyperammonemia?

Acquired (liver cirrhosis)

Hereditary (mental retardation usually occurs)

40

What transfers the most reduced (methyl) groups?

S-adenosyl methionine

41

What transfers intermediately reduced carbon groups?

Tetrahydrofolate

42

Is CO2 considered part of the one carbon pool?
How is it transferred?

NO

Biotin (vitamin B7)

43

Where does folic acid come from?
What is its structure?

Vitamin B9

pteridine ring, p-aminobenzoic acid (PABA), glutamate
(only bacteria make the link between pteridine and PABA)

44

What is ingested folic acid metabolized to?
What steps and enzyme involved?

Tetrahydrofolate (THF)

dihydrofoltate reductase

two reducing steps (using two NADPH)

45

Folic acid rxn:

Folic acid > dihydrofolate (NADPH>NADP+) > tetrahydrofolate (NADPH>NADP+)

46

What drug is an analog of dihydrofolate and important in cancer treatment?
What does it inhibit?

Methotrexate

enzyme of rxn: dihydrofolate reductase

47

What is the most common vitamin deficiency in the world?

Folate

48

What 3 molecules is tetrahydrofolate a requirement to metabolize?

Purine, Thymine, and AA metabolism

49

Where does THF usually get its carbon from?

(this is the major source of carried carbon)

Serine

(serine is converted to glycine in the process)

50

What rxn forms S adenosyl methionine (SAM)?
What catalyzes?

methionine + ATP

methionine adenosyl transferase

51

What does SAM carry?

ONE thing.

A methyl group

52

How is methionine formed?
enzyme?

Homocysteine + CH3 (from THF) > Methionine

methyltransferase

53

What is the rate limiting step of the active methyl cycle?

MTHFR

Methylene tetrahydrofolate reductase

54

Summarize the activated methyl cycle:

Methionine+ATP=SAM (methionine adenyl transferase) >
SAM donates methyl group (methyl transferase) >
SAHC (- adenosine by hydrolysis) >
Homocysteine methylated by methyl-THF (methionine synthase) >
Methionine

55

What provides the methyl-THF for the Homocysteine>methionine step in the methyl cycle?

What's the motherfuckin enzyme for this rxn?

Methyl THF

MTHFR

56

What creates the methyl trap?
What accumulates?

methyl-THF, once made, is irreversible

methyl FH4 (if not accepted by homocysteine)

57

What are 2 conditionally essential amino acids?

Tyrosine (from phenylalanine)

Cysteine (from homocesteine + serine)

58

Pyruvate + amine =
Oxaloacetate + amine =

Alanine
Aspartate

59

Alpha-ketoglutarate + amine =

What is the enzyme converting product to glutamine?

Glutamate

Glutamine synthetase

60

What is the pathway that produces cysteine and glycine?

3-Phosphoglycerate > Serine, then

1. with 1C transfer to THF via MTHFR > glycine
2. + homocysteine > cysteine

(remember, homocysteine comes from methionine, an essential AA)

61

What important molecule is made from cysteine?

Glutathione

(rids ROS in H2O2 pathway)

62

How is tyrosine made?
What enzyme (a deficiency in which causes PKU) is involved?

Phenylalanine >

phenylalanine hydroxylase

Tyrosine

63

What causes PKU?

autosomal recessive

phenylalanine hydroxylase dysfunctional

(phenylalanine cannot metabolize to tyrosine)

64

Where is Heme made and what is the limiting step?

Liver and bone marrow

DALA synthase is rate limiting step

65

What is the must-know step in Heme synthesis?
enzyme?
Where does it occur?

Succinyl CoA + Glycine > Delta aminolevulinate (DALA)

DALA synthase

mitochondria of liver and bone marrow

66

What is the coenzyme used for Heme synthesis and how is Heme production regulated?

pyridoxal phosphate (vitamin B6)

allosterically regulated by Heme

67

Myoglobin consists of a single _____, while hemoglobin consists of two ____.

polypeptide chain with 8 alpha helices

alpha/beta dimers

68

What is special about the Hba1c type of hemoglobin?

binds glucose non-enzymatically

69

How many heme groups are found on hemoglobin?
myoglobin?

4
1

70

Hemoglobin is most likely to accept oxygen in what conformation?
give oxygen?

Relaxed
T (taut)

71

What stabilizes the T-conformation of hemoglobin?
What does this do?

2,3 bisphosphoglycerate (a byproduct of glycolysis)

this makes it more likely hemoglobin will give up oxygen and deliver it to the tissues that need it the most. (airplane looking at smokestacks)

72

T/F
Over the physiological range of blood, myoglobin is usually saturated with oxygen.

True

73

What are the 3 main markers of metabolic industry that allosterically affect hemoglobin?

H+
CO2
2,3- bisphosphoglycerate

74

T/F
2,3 bisphosphoglycerate is released at the lungs

False

it is released before the lungs (only in smokers is the statement true)

75

What is the Bohr effect?

additive allosteric effects of H+ and CO2

76

CO2 reacts with terminal amine group on hemoglobin that forms _______ and stabilizes the T conformation.

Carbamate

(carbamate is also a CO2 carrier to the lungs)

77

What are 4 allosteric effectors of hemoglobin?

O2
H+
CO2
2,3 bisphosphoglycerate

78

How does carbon monoxide out compete oxygen?

Hemoglobin has a 200x affinity for CO

79

How does fetal hemoglobin differ from adult?

Fetal Hb has higher O2 affinity
does not bing 2,3 BPG

80

What accounts for about 14% of CO2 transport to the lungs?

carbamate
(RBC transport - rest goes as bicarbonate)

81

What is the major form of CO2 transport to the lungs?
What enzyme is involved?

CO2 to bicarbonate (HCO3-)

carbonic anhydrase (Zn)

82

What AA substitution creates sickle cell trait?

Valine for a glutamate in beta globin at 6th position

(glutamate kicks out valine - this is a polar for a nonpolar AA)

83

Does sickle cell train affect oxyhemoglobin state?

no

affects deoxy solubility

84

Nucleoside refers to:

Sugar and Base

85

What is the difference between deoxyribonucleotide and ribonucleotide?

Both are nitrogenous base (AGCTU), ribose sugar, phosphate

Deoxy is dehydroxylated at the C2 position in ribose

86

What is the difference between the salvage and De Novo pathways?

salvage - recycles

de novo - PPP > PRPP (activated ribose)

*de novo is expensive

87

What are the purines?
Pyrimidines?

A and G (two rings)
T, U, C

88

What does a nucleoside lack to be a nucleotide?

phosphate

89

Name 4 precursors for purine
(he would hate to ask this question)

CO2, glutamine, aspartate, glycine

need PRPP

90

What are the precursors for Pyrimidine?

Aspartate, glutamine, CO2

need PRPP

91

What is PRPP and how is it made?

phosphorylated x2 Ribose 5-P (from PPP)

PRPP synthetase

92

What is the first committed step in de novo purine biosynthesis?

What allosterically inhibits/activates?

PRPP > 5-Phosphorylribosyl-1-amine

via PRPP amidotransferase

allosterics:
ATP, ADP, AMPTP, GDP, GMP (different sites) inhibit (because purines)
PRPP activates

93

What is the function of PRPP?

Provides the activated sugar for synth

94

How do purine and pyrimidine synth from PRPP differ?

Purine builds onto sugar

Pyrimidine builds base and adds to sugar

95

What are the precursors and the committed step in de novo pyrimidine synthesis?

Aspartate, Glutamine, CO2

CPS II (carbamoyl phosphate synthetase II)

96

What are the 2 steps of de novo pyrimidine synth?

Carbamoyl formation
OMP

97

How is carbamoyl formed

remember: this is step 1 of de novo pyrimidine synth

2 ATP + bicarbonate + glutamine (for nitrogen) > Carbamoyl phosphate

via CPSII enzyme

98

What does carbamoyl phosphate combine with to form a pyrimidine ring?

Aspartate

99

What is the enzyme carbamoyl phophatase II inhibited/activated by?

inhibited - UTP

activated - ATP and PRPP

100

What are the parent molecules in purine and pyrimidine synth?

purine = IMP (inosine monophosphate)

pyrimidine = OMP (orotidine-5-monophosphate)

101

What are the rate limiting steps for purine and pyrimidine synth?

purine:
PRPP > 5-phophoribosylamine (PRPP amidotransferase)

pyrimidine:
HCO3- + NH3 (from glutamine) +2 ATP > carbamoyl phosphate (CPSII)

102

How are ribonucleotides converted to deoxyribonucleotides?

Step 1: RNR - ribonucleotide reductase (dehydroxylate my C2)
Step 2: thioredoxin (reduces OH)

then, NADPH regenerates thioredoxin via thioredoxin reductase

103

Urate causes gout. What is its soluble form?

Hypoxanthine

104

How does the Purine salvage pathway work?

Combine a base with PRPP

105

What are the two purine salvage pathways?

APRT: Adenine phosphorybosyl transferase (adenine + PRPP)

HGPRT: Hypoxanthine-Guanine phosphorybosyl transferase

106

Why is Pyrimidine salvage rare?
What enzyme is used if they are salvaged?

They usually degrade and excrete

Pyrimidine phosphoribosyltransferase

107

After pyrimidine phosphoribosyltransferase catalyzes PRPP onto a base, what is the next step?

U, T, and C are phosphorylated by their respective kinases

108

What is defective in Lesch Nyhan syndrome?

HGPRT enzyme (can't recycle purines)

this causes gout from too much uric acid

109

5 stages of cell cycle:

G0 - resting
G1 - growing (11 hrs)
S - DNA replication (8 hrs)
G2 - continued growth (4 hrs)
M - division

110

What's in a nucleosome?

8 Histone proteins

around each protein is wrapped 146 bp (1.75 turns)

111

T/F
In every instance, DNA replication requires an RNA primer.

True

112

How does the lagging strand replicate?

Still 5' to 3', but in Okazaki fragments

113

What is the function of DNA polymerase?

Catalyzes the formation of the sugar phosphate (backbone) connection in DNA

114

What are the 3 requirements for DNA polymerase to synthesize DNA?

1. ATCG (nucleotide triphosphates present)
2. Template strand
3. Primer

115

How big is the RNA primer and why is it needed?

10-20 nucleotides long

DNA polymerase can't initiate (but can continue)

116

What is the RNA primer made from?
Does it incorporate itself into DNA?

DNA polymerase alpha

No. It's removed and replaced after the strand has fully replicated

117

How many RNA primers does the leading strand have?
Lagging strand?

1
multiple (each okazaki fragment)

118

Why might it be better to be the lagging strand in replication?

Lagging strand doesn't get shortened (Okazaki's repair themselves at each fragmentation)

Leading strand doesn't replace primer with DNA. SHORTENS (only 50-80 mitotic divisions possible)

119

The primase/DNA polymerase use _____, but incorporate ______.

Triphosphates
Monophosphates

(attached to the pentose sugar)

120

What splices together Okazaki fragments?

DNA ligase

121

What are the terms Processivity and Fidelity mean pertaining DNA synthesis?

Processivity - enzyme ability to catalyze consecutive rxns (50k nucleotides)

Fidelity - very low error rate

122

How is high processivity attained in DNA synth?

Through RFC and PCNA (clamping mechanism)

123

What creates the replication fork? (two enzymes)

DNA helicase opens strand
Topoisomerase uncoils

124

Summarize leading strand synthesis:

RNA primer
RFC, PCNA, DNA Polymerase bind
nucleotides added, sliding down from 5' to 3'
RNA primer leaves hole
Telomerase (in some cases) repairs gap

125

Summarize lagging strand synth:

Multiple RNA primers
RFC, PCNA, DNA Polymerase
RNA primers leave and replaced by DNA polymerase
DNA ligase joins fragments

126

What is the only enzyme able to work with nucleoside monophosphates?

DNA ligase

127

What clinical technique uses palindromic sequences?

Restriction endonuclease

128

Blots:
Southern
Northern
Western
Eastern

DNA
RNA
Proteins
trick exam question

129

What are the 3 layers that ensure DNA replication accuracy?

Intrinsic fidelity (1/1000)
Proofreading (1/10 mil)
scanning enzymes/repair enzymes(1/1 billion)

130

What are the enzymes responsible for the immediate "proof reading" of DNA?

DNA polymerase makes error, stops
Exonuclease repairs

note: exonucleases go in both directions

131

What errors result in the following:
single replacement
stop codon
protein missing all or part of exon sequence
shifting sequence

missense
nonsense
RNA-splicing mutation
frameshift mutation

132

What is a trinucleotide expansion?

Mutation 3 bp's repeat

133

What are the 5 forms of DNA damage discussed in lecture?

Mispairing (wrong bases line up)
Depurination (A/G fall out)
Deamination (creates confusion in replication)
Chemical damage
UV damage (dimers, covalent bonds, nicks)

134

The addition of a methyl group to guanine (via chemical damage) causes it to pair with what (instead of cytosine)?

Thymine

135

UV light, in particular, causes damage in the form of covalent bonding in what dimer?

TT

(thymines) 90% of UV damage

136

What is the enzyme used in the Direct Reversal of methylated Guanine?

O6-methyguanine methyltransferase

137

What is the main enzyme used in the very specific type (single base) excision repair?

Gycosylase

138

What 3 steps (4 enzymes) are used in the excision repair of longer strips of DNA?

Nuclease
DNA Helicase
DNA Polymerase + DNA Ligase

139

When can double-stranded DNA breaks be repaired and what process utilizes this?

During replication
Homologous/non-homologous recombination

140

A defect in the nucleotide excision repair system leads to what pathology?

Xeroderma Pigmentosum

141

What is the major watchman of the cell (defect of which is found in 50% of cancer patients)?
What does this watchman normally do?

p53 pathway

programs cell apoptosis

142

What is the class of eicosanoid derived from Omega 6 linoleic acid?

Arachidonic Acid

143

What is the class of eicosonoid derived from Omega 3 linolenic acid?

Eicosapentanoic acid (EPA)

144

What end is the modified G nucleotide attached to in RNA?
What end are the A nucleotides attached to in RNA?

5' (G)
3' (AAAA's)

145

What is the process of exon shuffling to make RNA strands (and therefore different proteins)?

Alternative splicing

146

What is a promoter?
What are two gene sequence features?

A region of DNA that initiates transcription of a certain gene.

TATA box and CAAT box (sometimes GC)

147

What does hnRNA signify?

The cap site (PyAPy)

148

What does the protein start and stop signal look like on DNA/RNA?

ATG - TGA (DNA)
AUG - UGA (RNA)

149

Describe mRNA from 5' to 3' (anatomy).

5' cap - AUG - (coding sequence) - UGA - poly A tail - 3'

150

What sequence denotes the cap site (where transcription begins)?

ACATTTG

151

The promoter region, consisting of the TATA (or CAAT) box, is responsible for binding what?

RNA polymerase

152

What are the two areas found within promoter sites in eukaryotes?
How big is the promoter site?

CAAT and GC are the upstream activating sequences
TATA box

100 bp long

153

If RNA polymerase is the helicopter, the promoter is the...

helipad

154

What determines the specificity of transcription of a certain gene?

the Promoter

155

How many types of RNA polymerase are there in eukaryotes?

3

156

What is the name of a family of transcription factors?

C/EBP's (CCAAT-enhancer)

157

What do enhancers do?

open up chromatin, recruit other enhancers

And physically contacts promoter

158

What does the Leader Sequence refer to?

the 50 bp's preceding the ATG start codon

159

What is the translation termination codon?
What follows it?

TAA
poly A tail

160

Are promoters transcribed?

No. they designate where transcription begins and are just upstream

161

What binds the promoter sequence before RNA polymerase can bind?

Transcription factors

162

What is the basal transcription apparatus?

The promoter, transcription factors, and RNA pol II acting together

163

What proteins interact with the basal transcription apparatus to regulate the transcription rate?

Activator proteins

164

What type of RNA stays in the nucleus and regulates other RNA?

snRNA

165

What is the mediating factor between RNA pol II and promoter sites?

Transcription factors

166

What direction does RNA polymerase travel?

5' to 3'

167

Does RNA polymerase require a primer?

no

168

T/F
RNA polymerase unwinds, transcribes, and rewinds DNA

True

169

When does the elongation phase of transcription end?

When termination signal reached

170

What does the 5' cap and the 3' tail consist of?

methylated guanosine

200 A tail

171

Where is RNA pol I found?

nucleolus

172

Which RNA is the major one in mammals?

rRNA (85%)

173

What 3 sites must be in place for proper splicing and removal of introns?

5' splice site (GUA)
Branch site (A)
3' splice site (AG)

174

What is the function of snRNP's?

bind introns (at 3 sites)

175

What is the structure of tRNA

coverleaf (secondary H-bond structure)
covalent ester bond to AA
anti-codon

176

What do all tRNA have at their 3' terminus?

CCA - then ester bond to AA

(5' doesn't connect to anything)

177

How many nucleotides long is tRNA

70-80

178

What binds tRNA to Amino Acids?
(the matchmaker)

Aminoacyl tRNA synthetase

179

How many aminoacyl tRNA synthetases are there?

20

180

What are the two components of the ribosome?
What do they make when combined?

40S and 60S

80S

181

What ribosome binds the mRNA codon

40S

182

What does the tRNA capable of initiating translation carry?

methionine

183

What recognizes met-tRNA and binds it to the 40S ribosomal unit?

note: at least 10 of these are required to initiate translation

Eukaryotic initiation factor 2

184

During initiation of translation, what attaches to the methyl-guanosine cap at the 5' end?

Cap binding proteins
eukaryotic factors 4A and 4B

185

What needs to occur before the 60S ribosomal subunit binds in translation?

The 40S needs to travel down to the AUG start codon

186

AUG is start codon. What is start anticodon?

CAU

187

What are the 3 binding sites in a ribosome?

A (aminoacyl)
P (peptidyl)
E (Exit)

188

What brings the tRNA to the A-site?
(like an usher)

EF-Tu

(with GTP)

189

What regenerates the spend EF-Tu GDP after ushering a tRNA?

EF-Ts

190

What are the 3 stop codons and what recognizes these?

UAA UAG UGA

Release factors

191

What do release factors bind to?

The termination codon

(UAA UAG UGA)

192

Where does the unusual base pairing occur according to the wobble hypothesis?

3rd base codon (1st base anticodon)

(variability occurs in 3rd base codon)

193

What is the function of Ferritin?

binds iron

194

What happens to Ferritin if iron is scarce?

IRE-BP binds IRE (Iron Response Element), blocking translation of Ferritin

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