Amino Acid Metabolism

Question 1

3 key cofactors for enzymes in AA metabolism

Answer 1

PLP: transaminase

Tetrahydrafolate (FH4-): 1 C transfers

Tetrahydrobiopterin (BH4): Ring hydroxylations (Phe–>Tyr)

Question 2

True false, AA biosynthesis and degredation use only one enzyme

How many essential/non-essential AAs?

Answer 2

False

11 non- body can make

9 need to acquire in diet (10 for kids***)

Question 3

Essential AAs

Answer 3

M.V. Pitthall

Methionine
Valine
Phenylalanine
Isoleucine
Tryptophan
Threonine
Histidine
Arginine *
Leucine
Lysine

Question 4

What’s unique about tyrosine?

Answer 4

Tyrosine, a non-essential amino acid, requires dietary phenylalanine for synthesis. In the absence of phenylalanine hydroxylase, tyrosine becomes an essential amino acid.

Tyrosine gets an OH- group from Phe via phenylalinine hydroxylase.

Question 5

What’s unique about cysteine?

Answer 5

Similarly, the biosynthesis of the nonessential amino acid cysteine requires dietary methionine to donate sulfur.

Question 6

What role does BH4 play in conversion of Phe–>Tyr?

Answer 6

BH4 transfers e-’s from cofactor to H2O.

Question 7

Glycolysis substrates –> what AA’s?

Answer 7

Pyruvate –> Ala via transamination.

3-PG –> Serine –> cysteine

Serine also <–> glycine

So, 4 AA’s can ultimately come from glycolytic intermediates.

Question 8

What cofactor transfers Serine’s side chain to make the simplest AA, Gly?

How else can Ser be made?

Answer 8

Tetrahydrofolate (FH4-)

Serine can also be produced by b-elimination from dietary threonine

Question 9

______ results from inherited mutations (autosomal recessive) in the amino acid carrier for cysteine and basic amino acids (lysine, arginine and ornithine).

Answer 9

Cystinuria.

…When transporters are defective, Cys can’t come back out of kidney lumen. It precipitates there, forming kidney stones

Question 10

_____ and a _____ from homocysteine are joined to make cysteine.

Degradation of cysteine forms either _____ or _____.

Answer 10

Serine & sulfur from homocysteine –> Cys

Sulfuric acid: acidifies urine –WAY BODY CAN MODULATE PH OF URINE

PAPS: An “activated sulfate” for use in other reactions. – Can donate SO4’s in other rxns

Question 11

Alanine is the major ______ amino acid. It is transaminated by ______ to pyruvate.

Answer 11

Ala = the gluconeogenic AA

alanini aminotransferase (ALT)

Question 12

Where does ALT normally exist? If in the blood, it means what?

Answer 12

ALTs are liver enzymes that convert Ala to pyruvate and vice versa. ALT in blood means liver impairment

Question 13

AA’s derived from TCA cycle:

Answer 13

OAA –> Aspartate –>Asparagine

alpha-KG –> glutamate, which can –> Pro & Arg…glutamate also–> glutamine

Question 14

Again, AA’s derived from TCA:

Answer 14

From a-ketoglutarate:
glutamate
glutamine
arginine
proline

From oxaloacetate:
aspartate
aparagine

Question 15

OAA–> Asn

Answer 15

Question 16

Glu –> alpha-KG via GDH

Answer 16

Glutamate can be produced from a-ketoglutarate through reductive deamination by glutamate dehydrogenase.

Question 17

Another way to convert Glu –> alpha-KG:

Answer 17

Glutamate can also be produced from a-ketoglutarate through transamination by aspatate aminotransferase (AST).

Question 18

Glu –> Gln

Answer 18

Glutamine synthetase is one of three ammonium fixing enzymes. Glutamine is an important inter- tissue transporter of nitrogen.

Question 19

All amino acids synthesized from TCA cycle intermediates can be degraded to TCA cycle intermediates.

Essential amino acids can also degrade to TCA cycle intermediates and ketone bodies.

Answer 19

Question 20

______degradation requires a tetrahydrofolate for conversion to glutamate. In folate deficiency, what accumulates.

Answer 20

Histidine requires FH4

In folate deficiency, an intermediate of histidine degradatin, FIGLU, accumulates

Question 21

Which AA’s are ketogenic?

Answer 21

Thr, Lys, Iso and Trp

Question 22

AA’s found elevated in Maple Syrup Disease:

Answer 22

Branch chain AA’s - Iso, Val, Leu: Maple syrup urine disease

Question 23

WHat enzyme is defective in Maple Syrup Disease?

What characterizes this disease and what AA’s are involved?

Answer 23

Autosomal recessive deficiency in branched chain a-keto acid dehydrogenase

Classic: Presents in infants 1 week old with convulsions, vomitting, maple syrup odor in urine. Fatal if no tx

Labs: Elevated plasma and urine Val, Iso, Leu and keto-acids
Often hypoglycemic
Often ketoacidosis

Treatment:
Acute: hydration, transfusion
Long term: synthetic low BCAA diet

Question 24

What about mild and intermittant forms of Maple Syrup Disease?

What tx and why?

Answer 24

Intermittant
sporadic bouts of MSUD

Mild
mental retardation

High dose thiamin increases TPP to help out moderately and mildly malfunctioning dehydrogenase enzyme at E1 subunit. Swamping it w/ cofactor gives enzyme best chance to work. Similar to PDH, alpha-keto acid dehydrogenase is inactivated when phosphorylated and active w/o PO4 bound.

Question 25

Why do lab values for one form of Autism show low serum concentrations of branch chain AAs? What likely leads to sx?

Answer 25

Patients have low branch chain AA’s cuz kinase enzyme is knocked out.

Alpha-keto acid dehydrogenase is always on to decarboxylate these AA’s. Either deficit in protein synthesis necessary for neuronal tissue or E-deficit from inability to derive E from branch chain AA’s during development.

Question 26

What enzyme is defective in the form of Autism and what one in Maple Syrup Disease?

Answer 26

Autism: keto acid dehydrogenase kinase is responsible for a combined autism / seizure disorder.

MSD: a-keto acid dehydrogenase.

Question 27

What does Phe and Tyr degradation lead to for products?

Answer 27

Phenylalanine and tyrosine can be degraded to the TCA cycle intermediate fumarate and the ketone body acetoacetate.

Question 28

Phenylketonuria (PKU)

Answer 28

A defect in phenylalanine hydroxylase prevents tyrosine biosynthesis.
*Phe accumulates in the brain and blood. Tyrosine becomes an essential AA.
Symptoms: Infants are normal at birth, and gradually develop seizures, cognitive delay, light complexion, “mousy” odor (from phenylacetate).
Diagnosis: All infants born in the US are screened for blood phenylalanine and tyrosine concentrations using tandem MS/MS.
Treatment: Phenylalanine restricted diet.

Question 29

Tyrosinemia (Type II)

Answer 29

A rare autosomal recessive mutation of tyrosine aminotransferase.

Patients develop plaques on the hands and feet, corneal ulcers, and frequent mental retardation.

Labs: Serum tyrosine is elevated to 20-50 mg/dL (normal = 1 – 4 mg/dL)

Treatment: Synthetic diet low in phenylalanine and tyrosine

Question 30

Alcaptonuria

Answer 30

Deficiency in homogentisate oxidase.

Homogentisate accumulates and is excreted in urine, giving it a dark color. Patients are asymptomatic until middle age, when they develop arthritis, back pain, renal calculi.

Diagnosis:
Ochronosis (dark spots of polymerized homogentisic acid in the sclera and ear cartilage)
Homogentisic acid in urine.
Tx is just sx management for pain and stones

Question 31

Tyrosinemia (Type I)

Answer 31

Disorder of fumaryloacetoacetate hydrolase (FAH) results in accumulation of succinlyacetone.

Presents as acute hepatic crisis, usually at 2-4 months of age: Jaundice, hepatomegaly, elevated AST & ALT, hypoglycemia

Diagnosis: Succinylacetone in urine and blood

Treatment: Nitosinone