M&n Week 2: Disorders Of Amino Acid Metabolism

Front 1

What are the two conditionally nonessential amino acids?

Which essential amino acids are these derived from?

Back 1

1. Tyrosine <--phenylalanine
2. Cysteine <--methionine

Front 2

What type of nitrogen balance is demonstrated by:
Anabolism > Catabolism ?

Back 2

Positive nitrogen balance

Front 3

What type of nitrogen balance is demonstrated by:
Anabolism < Catabolism ?

Back 3

Negative nitrogen balance

Front 4

Pregnancy or recovering from starvation are examples of what type of nitrogen balance?

Back 4

Positive nitrogen balance
(anabolism > catabolism)

Front 5

Starving or a deficiency of one or more amino acids in the diet are examples of what type of nitrogen balance?

Back 5

Negative nitrogen balance
(Anabolism < Catabolism)

Front 6

Which enzyme performs the following rxn?

a-ketogluterate + amino acid <--?---> glutamate + a-keto acid

What type of reaction is this?

Back 6

Aminotransferase

*Transamination rxn.

Front 7

Alanine can be transformed to which a-keto acid?

Back 7

Pyruvate

Front 8

Pyruvate is derived from which amino acid?

Back 8

Alanine

Front 9

In a transamination reaction, the a-ketogluterate is aminated to form which amino acid?

Back 9

Glutamate

Front 10

What happens during a transamination reaction?

Back 10

Amino acid is deaminated --> a-keto acid
a-ketogluterate is aminated --> glutamate

Front 11

Which enzyme converts alanine to pyruvate?

Back 11

Alanine aminotransferase

Front 12

Which enzyme converts aspartate to oxaloacetate?

Back 12

Aspartate aminotransferase

Front 13

Aspartate is converted to which a-keto acid in a transamination reaction?

Back 13

Oxaloacetate

Front 14

Are aminotransferases specific or nonspecific?

Back 14

Specific (for one or a few amino acids)

Front 15

Are aminotransferases reversible or irreversible?

Back 15

Reversible

Front 16

What is the diagnositic significance of aminotransferases?

Back 16

Both alanine AT and aspartate AT are elevated in liver diseases, myocardial infarctions, and muscle disorders

Front 17

Which coenzyme is required for all aminotransferases?

This is the coenzyme form of which vitamin?

Back 17

Pyridoxal phosphate (PLP)

Vitamin B6

Front 18

Pyridoxal phosphate (PLP) is a coenzyme for which group of enzymes?

Back 18

Aminotransferases

Front 19

Pyridoxal phosphate is covalently attached to which portion of its associated enzyme?

Back 19

Lysine sidechain of the active site of the aminotransferase

Front 20

What is the function of PLP?

Back 20

Acts as an intermediate carrier of the transferred amino group during transamination reactions

Front 21

What is pyridoxal pyrophosphate (PLP) converted to during a transamination reaction?

Back 21

Converted to pyridoxamine phosphate (PMP) upon acceptance of amino group

Front 22

Which enzyme is responsible for oxidative deamination?

Back 22

Glutamate dehydrogenase

Front 23

Which enzyme performs the following rxn:

L-glutamate + H2O ---?---> a-ketoglutarate + NH4

Back 23

Glutamate dehydrogenase

Front 24

Glutamate dehydrogenase uses which coenzymes?

Back 24

Can use either NAD+ or NADP+

Front 25

Which type of a reaction does glutamate dehydrogenase perform?

Back 25

Oxidative deamination

Front 26

What are the allosteric inhibitors of glutamate dehydrogenase?

Back 26

1. ATP
2. GTP

Front 27

What are the allosteric activators of glutamate dehydrogenase?

Back 27

1. ADP
2. GDP

Front 28

What is the corresponding a-keto acid of glutamate?

Back 28

a-ketogluterate

Front 29

Which 2 amino acids serve to transport nitrogen from other organs and tissues to the liver?

Back 29

1. Alanine
2. Glutamine

Front 30

Which amino acid is the major form in which nitrogen is transported from muscle tissue to the liver?

Back 30

Alanine

Front 31

What is the name of the cycle that transports nitrogen from the muscle tissue to the liver?

Back 31

Glucose-Alanine cycle

Front 32

Which enzyme converts glutamate to glutamine?

Back 32

Glutamine synthetase

Glutamate + NH4+ ---> Glutamine

Front 33

Which enzyme converts glutamine to glutamate?

Back 33

Glutaminase

Front 34

Which amino acid can directly use NH4+ in its synthesis?

Back 34

Glutamine

(via glutamine synthetase)

Front 35

In the case of high levels of ammonia, what happens to the levels of a-ketogluterate, glutamate, and glutamine?

Back 35

Decreased a-ketogluterate
Decreased glutamate
Increased glutamine

Front 36

What type of compound is formed by the removal of NH4+ from an amino acid?

Back 36

a-keto acid

Front 37

What is the rate-limiting step of the Urea Cycle?

Back 37

Carbamoyl phosphate synthetase-1

Front 38

Where are the enzymes that participate in the urea cycle located?

Back 38

Mitochondrial matrix and cytosol

Front 39

Where is carbamoyl phosphate synthetase I located?

Back 39

Mitochondrial matrix

(rate limiting enzyme in urea cycle)

Front 40

CO2 + NH4+ --?--> carbamoyl phosphate

Back 40

Carbamoyl phosphate synthetase I

(rate limiting step in urea cycle)

Front 41

L-ornithine + carbamoyl phosphate --?--> L-citrulline

Back 41

Ornithine transcarbamoylase

Front 42

Where is ornithine transcarbamoylase located?

Back 42

Mitochondrial matrix

(urea cycle enzyme)

Front 43

L-Citrulline + L-Aspartate --?--> Argininosuccinate

Back 43

Argininosuccinate sythetase

Front 44

Where is argininosuccinate synthetase located?

Back 44

Cytosol

(urea cycle enzyme)

Front 45

Argininosuccinate --?--> L-Arginine + Fumarate

Back 45

Argininosuccinate lyase

Front 46

L-Arginine --?--> Urea + L-Ornithine

Back 46

Arginase

Front 47

Where is arginase located?

Back 47

Cytosol

(urea cycle enzyme)

Front 48

Which enzyme of the urea cycle finally results in the formation of urea?

Back 48

Arginase

Front 49

Where do the two nitrogen atoms in urea come from?

Back 49

1. NH4+
2. Aspartate (added to L-citrulline by argininosuccinate synthetase to make argininosuccinate)

Front 50

How many moles of nitrogen are present in urea?

Back 50

two

(from ammonia and aspartate)

Front 51

What activates carbamoyl phosphate synthetase I (CPS I)?

Back 51

N-acetylglutamate

Front 52

Where do nitrogen atoms in the urea cycle originate from?

Back 52

Glutamate

Front 53

Which enzyme forms N-acetylglutamate?

What is the significance of this compound?

Back 53

N-acetyalglutamate synthetase

*Activates carbamoylphosphate synthetase I

Front 54

Which compound yields the allosteric activator of carbamoylphosphate synethetase I (CPS I)?

Back 54

Glutamate

Front 55

Which compound is a precursor of ornithine?

Back 55

Glutamate

Front 56

What is the immediate precursor of urea?

Back 56

Arginine

Front 57

Which compounds are transported between the mitochondrial matrix and the cytosol during the urea cycle?

Back 57

Ornithine and citrulline

Front 58

When energy levels are low within the cell, amino degradation by glutamate dehydragenase is _____ (high/low)?

Back 58

High
(Facilitates energy production from the carbon skeletons derived from amino acids)

Front 59

Which amino acid is the only one that undergoes rapid oxidative deamination?

Back 59

Glutamate

Front 60

After ingestion of a meal containing protein, are glutamate levels in the liver increased or decreased?

How does this affect the direction of amino acid degradation?

Back 60

Glutamate levels are INCREASED

Reaction proceeds towards amino acid degradation and the formation of ammonia

Front 61

Which of the urea acid cycle enzymes occurs almost exclusively in the liver?

Back 61

Arginase
(only the liver can cleave arginine, thereby synthesizing urea)

Front 62

What is the most common urea cycle disorder?

Back 62

OTC
(ornithine transcarbamoylase)

Front 63

In OTC, which plasma amino acids are elevated and which are decreased?

Back 63

1. Glutamine <---elevated
2. Alanine <---elevated
3. Citrulline <----decreased
4. Arginine <--- decreased

Front 64

What happens to urine orotic acid levels in deficiencies of OTC?

Back 64

Increased levels

(due to increased levels of carbamoyl phosphate, which can then be used in pyrimidine synthesis)

Front 65

List two alternate pathways for nitrogen excretion that are utilized when certain urea enzymes are deficient.

Back 65

1. Sodium benzoate conjugates with glycine ---> hippurate

2. Phenylbutyrate is converted to phenylacetate, which becomes conjugated to glutamine to form phenylacetylglutamine.

*These products are excreted in the urine

Front 66

Which amino acid is a precursor of glycine?

Back 66

Serine

Front 67

What is the short term goal in treating hyperammonemia?

Back 67

Decrease levels of ammonia.
This is accomplished by administering benzoate or phenylbutyrate

Front 68

What is the long term treatment of hyperammonemia?

Back 68

Low protein diet

Front 69

Which amino acids are both glucogenic and ketogenic?

Back 69

1. Isoleucine
2. Tryptophan
3. Tyrosine
4. Phenylalanine

Front 70

Which amino acids are only ketogenic?

Back 70

1. Leucine
2. Lysine

Front 71

In general, what type of amino acids are ketogenic?

Back 71

Amino acids that are degraded to acetyl-CoA or acetoacetyl-CoA

Front 72

Amino acids that are degraded to produce intermediates of the TCA cycle are referred to as ....?

Back 72

Glucogenic amino acids
(carbon skeletons can be used for the synthesis of glucose)

Pyruvate, a-ketogluterate, succinyl-CoA, fumarate, oxaloacetate

Front 73

Phenylketouria reflects a defect in the catabolism of which amino acid?

Back 73

Phenylalanine

Front 74

Maple Syrup Urine Disease reflects defects in catabolism of which amino acids?

Back 74

Isoleucine, leucine, and valine

Front 75

Homocystinuria reflects a defect in the catabolism of which amino acid?

Back 75

Methionine

Front 76

The catabolism of which amino acid is the one exception where transamination is NOT the first step of the pathway?

What is the first step?

Back 76

Phenylalanine

First step: hydroxylation to form tyrosine

Front 77

The hydroxylation of phenylalanine to tyrosine is performed by which enzyme?

Back 77

Phenylalanine hydroxylase

Front 78

Which enzyme is deficient in PKU?

Back 78

Phenylalanine hydroxylase

Front 79

What is the second step in the catabolism of phenylalanine?

Back 79

Transamination of tyrosine

(the first step is the hydroxylation of phenylalanine to tyrosine)

Front 80

Which cofactor is required for the function of phenylalanine hydroxylase?

Back 80

BH4 (tetrahydrobiopterin)

Front 81

Which enzyme converts BH2 back to BH4?

Back 81

Dihydropteridine reductase

Front 82

What is the genetic inheritance pattern of PKU?

Back 82

Autosomal recessive

Front 83

Which enzyme is deficient in 99% of cases of PKU?

Which enzyme is deficient in 1% of cases?

Back 83

99%--> Phenylalanine hydroxylase

1% --> Dihydropteridine reductase (DHPR)

Front 84

If untreated, what are the clinical symptoms seen in PKU?

Back 84

1. Mental retardation
2. CNS damage
3. Hypopigmentation

Front 85

What is the treatment for PKU?

Back 85

Restriction of phenylalanine from diet and addition of tyrosine to diet (tyrosine becomes essential).

Front 86

Which neurotransmitters are deficient in DHPR deficiency?

Back 86

Dopamine and Serotonin

tyrosine --(BH2--BH4)--> L-dopa ---> dopamine

tryptophan --(BH2-->BH4) --> 5-hydroxytryptophan --> serotonin

Front 87

What supplements should be taken by patients with a DHPR defciency?

Back 87

BH4, L-dopa, and 5-hydroxytryptophan

Front 88

In PKU, what are the metabolic consequences of phenylalanine?

Back 88

Phenylalanine is converted to phenylpyruvate when is then converted to:
1. Phenyllactate
2. Phenylacetate

Front 89

In PKU, will a patient have high or low levels of phenyllactate and phenylacetate?

Back 89

HIGH

Front 90

List 4 types of biosynthetic products of tyrosine that are deficient in patients with PKU.

Back 90

1. Proteins
2. Melanin <---results in hypopigmentation
3. Catecholamine
4. Fumarate

Front 91

Why do patients with PKU have hypopigmented skin?

Back 91

Low levels of melanin due to decreased tyrosine

Front 92

What type of mutation usually occurs in the phenylalanine hydroxylase gene, resulting in PKU?

Back 92

missense mutation

Front 93

Which branched-chain amino acids build up due to a defect in the branched-chain a-keto acid dehydrogenase?

Back 93

1. Isoleucine
2. Leucine
3. Valine

Front 94

Which step in the catabolism of branched-chain amino acids is disabled due to a defect in branched-chain a-ketoacid dehydrogenase?

What type of reaction is this?

Back 94

SECOND STEP

Oxidatiive decarboxylation

Front 95

List the general steps involved in the catabolism of branched-chain amino acids

Back 95

1. Branched-chain amino acids undergo transamination resulting in a-keto acids
2. a-keto acids undergo oxidative decarboxylation performed by a-keto acid dehydrogenase
3. ketogenic and glucogenic end products

Front 96

Defects in the catabolism of branched-chain amino acids will result in increases in which type of compounds?

Back 96

1. Isoleucine, Leucine, Valine
2. a-keto acids

Front 97

What is the inheritance pattern of Maple syrup urine disease?

Back 97

Autosomal recessive

Front 98

What disorder results from a deficiency of branched-chain a-keto acid dehydrogenase complex?

Back 98

Maple syrup urine disease

Front 99

What symptoms are seen in maple syrup urine disease?

Back 99

(onset within 4-7 days of birth)
1. Lethargy
2. Weight loss
3. Damage to CNS
4. Coma --> death (or survivors suffer from mental retardation)

Front 100

Which compound is responsible for the maple syrup smell of urine associated with MSUD?

Back 100

a-keto acid of Isoleucine (2-oxo-3-methylvaleric acid)

Front 101

How is MSUD diagnosed?

Back 101

1. Large increase in levels of branched-chain amino acids in plasma and urine (particularly leucine)
2. Presence of a metabolite of isoleucine (alloisoleucine) in the plasma and urine

Front 102

How can MSUD result in secondary hyperammonemia?

Back 102

Organic acids (a-keto acids) that build up can inhibit N-acetylglutamate synthetase
This enzyme is responsible for making N-acetylglutamate which is essential for activating the first step in the urea cycle

Front 103

Describe the conversion of methionine to cysteine.

Back 103

Met --> homocysteine --> cystathionine --> cysteine + a-ketobutyrate

Front 104

Which Vitamin functions as a cofactor for cystathionine synthase?

Back 104

Vitamin B6

Front 105

What is the genetic inheritance pattern of homocystinuria?

Back 105

Autosomal recessive

Front 106

Which enzyme is deficient in homocystinuria?

Back 106

Cystathionine synthase

Front 107

Osteoporosis, mental retardation, and lens dislocation are all associated with which metabolic disorder?

Back 107

Homocystinuria

(can also lead to vascular problems, putting patients at risk for heart attacks)

Front 108

How is homocystinuria diagnosed?

Back 108

Accumulation of homocysteine in the urine

Front 109

What kind of treatments are useful some cases of homocystinuria (those involving mutations in the catalytic site of cystathionin synthase)?

Back 109

(In some cases, a mutation in the active site of the enzyme will result in a decreased affinity for the B6 cofactor)

1. Megadoses of Vitamin B6
2. Supplements of Vitamin B12 and folic acid (drives reaction homocysteine --> methionine, reducing amount of homocysteine)

Front 110

a-ketogluterate leads to the synthesis of which amino acids?

Back 110

1. Glutamate
2. Glutamine
3. Proline

Front 111

Oxaloacetate leads to the synthesis of which amino acids?

Back 111

1. Aspartate
2. Asparagine

Front 112

Pyruvate is a precursor of which amino acid?

Back 112

Alanine

Front 113

3-phosphoglycerate leads to the synthesis of which amino acids?

Back 113

1. Serine
2. Cysteine
3. Glycine

Front 114

Phenylalanine is a precursor of which amino acid?

Back 114

Tyrosine

Front 115

What are the 5 precursors that lead to the synthesis of nonessential amino acids?

Back 115

1. a-ketogluterate
2. Oxaloacetate
3. Pyruvate
4. 3-phosphoglycerate
5. Phenylalanine

Front 116

How is glutamate synthesized from its precursor a-ketogluterate?

Back 116

Reductive amination
(performed by glutamate dehydrogenase)

a-ketogluterate + NH4+ ---> glutamate

Front 117

What is the affect of high concentrations of ammonia on the reductive amination reaction?

Back 117

Drives it forward

a-ketogluterate + NH4+ --> glutamate

Front 118

How is alanine synthesized from pyruvate?

Back 118

Transamination reaction performed by alanine aminotransferase

pyruvate + glutamate --> alanine + a-ketogluterate

Front 119

How is glutamine synthesized from glutamate?

Back 119

Glutamine synthetase

Glutamate + NH4+ --> glutamine

Front 120

How is Asparagine synthesized from Aspartate?

Back 120

Asparagine synthetase

aspartate + glutamine ---> asparagine + glutamate

Front 121

The nitrogen component of serine comes from which amino acid?

Back 121

Glutamate
(donates amine group via transamination--> 2nd step in serine synthesis)

Front 122

Tetrahydrofolate is composed of which 3 units?

Back 122

1. Pteridine derivative
2. p-aminobenzoic acid (PABA)
3. Glutamic acid

Front 123

How are carbon fragments carried on THF?

Back 123

Carried on either the N5 or N10 atoms of THF or as a bridge between both.

Front 124

Tetrahydrofolate is an acceptor of a 1-carbon unit in the synthesis of which amino acid?

Back 124

Glycine

Front 125

N5-methyl-FH4 is a donator of a 1-carbon unit in the synthesis of which amino acid?

Back 125

Methionine

Front 126

Tremors, slurring of speech, and blurred vision are symptoms associated with what type of metabolic disorder?

Back 126

Hyperammonemia

Front 127

How can hyperammonemia be acquired?

Back 127

Liver diseases (cirrhosis, hepatitis..)

Front 128

When should blood phenylalanine levels be measured to screen for PKU?

Back 128

>2 days after birth