Biochemistry - Metabolism - Proteins and stuff

Question 1

Which amino acids are “essential” amino acids?

Answer 1

Glucogenic: Methionine, Valine, Histidine
Glucogenic/ketogenic: Isoleucine, Phenylalanine, Threonine, Tryptophan
Ketogenic: Leucine, Lysine

Question 2

Which amino acids are acidic?

Answer 2

Aspartic acid, Glutamic acid. (Neg at body pH).

Question 3

Which amino acids are basic?

Answer 3

Arginine, Lysine, Histidine.

Question 4

Which amino acids are required during periods of growth?

Answer 4

Arg and His

Question 5

Which amino acids are in histones?

Answer 5

Arg and Lys.

Question 6

What is the purpose of the urea cycle?

Answer 6

In order for the carbon skeletons of amino acids to be broken down and used as energy the nitrogen must be removed; the urea cycle converts nitrogen into urea so it can be excreted.

Question 7

What is the basic structure of an amino acid?

Answer 7

H2N-CH-COOH with an R group coming off the middle C. The R group distinguishes the amino acid.

Question 8

What is the structure of carbamoyl phosphate?

Answer 8

CO2 + NH3 –(ATP)–> H2N-COO-phosphate

Question 9

What is required for the conversion of CO2 + NH3 to carbamoyl phosphate?

Answer 9

N-acetylglumatate, 2ATP + carbamoyl phosphate synthetase

Question 10

What is the structure of urea?

Answer 10

H2N-CO-NH2

Question 11

What is the role of alanine/glutamate in taking nitrogen from amino acid to urea?

Answer 11

In Muscle: Amino acid (NH3) —> glutamate (NH3) –> Alanine (NH3). Alanine can be transported to Liver where it can become pyruvate/glucose, donating NH3 back to glutamate, which becomes urea.

Question 12

What is alpha-ketoglutarate critical for?

Answer 12

1) Picks up ammonia from aspartate to become glutamate

2) Intermediate in TCA.

Question 13

What does hyperammonemia deplete and lead to?

Answer 13

Leads to depletion of alpha-ketoglutarate, leading to inhibition of TCA.

Question 14

What are the symptoms of hyperammonemia?

Answer 14

tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Question 15

What are the treatments for hyperammonemia?

Answer 15

1) limit protein in diet
2) lactulose acidifies the GI tract and tracts NH4+ for excretion
3) Rifaximin decreases colonic ammoniagenic bacteria
4) Benzoate/phenylbutyrate bing amino acid and lead to excretion, can decrease ammonia levels.

Question 16

What is n-acetylglutamate synthase deficiency?

Answer 16

N-acetylglutamate is a required cofactor for CAP synthetase I, which brings ammonia into the urea cycle. Absence –> hyperammonemia.

Question 17

How does n-acetylglutamate present? What other deficiency does it look identical to?

Answer 17

In infants as poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability; identical to presentation of CAP synthetase I deficiency.

Question 18

What is ornithine transcarbamylase deficiency?

Answer 18

Most common urea cycle disorder, X-linked recessive. Ornithine + CAP –> citruline via OTC. Cannot eliminate ammonia, CAP excess converted to orotic acid (pyrimidine synthesis pathway).

Question 19

What are the findings in OTC deficiency?

Answer 19

Usually presents in first few days of life, may present later. Increased orotic acid in blood and urine, decreased BUN, sx of hyperammonemia. Diff from orotic aciduria bc no megaloblastic anemia (caused by insufficient pyrimidine).

Question 20

What is the defect in PKU?

Answer 20

Phenylketonuria is autosomal recessive defect in phenyalanine hydroxylase or BH4 (malig). Cannot synthesize Tyrosine, building by phenyalanine, excess in urine.

Question 21

Findings of PKU, Treatment:

Answer 21

Sx: Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Newborn screening 2-3 days after birth (normal at birth bc of maternal enzyme).
Tx: Decrease phenylalanine in diet, increase tyrosine. Supplement BH4. Cannot have aspartame (contains phenylalanine).

Question 22

Maternal PKU

Answer 22

Lack of proper dietary therapy during pregnancy. Findings in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects.

Question 23

Maple Syrup Urine Disease defect

Answer 23

Autosomal recessive blocked degradation of branched amino acids. I Love Vermont = Isoleucine, *Leucine, Valine. Caused by deficient alpha-ketoacid dehydrogenase (b1). Causes increased alpha ketoacids in blood.

Question 24

Maple Syrup Urine Disease findings and treatment

Answer 24

Findings: Urine smells like maple syrup. Causes severe CNS defects, intellectual disability, and death. Restriction of Isoleucine, leucine, valine in diet, thiamine (b1) supplementation.

Question 25

Alkaptonuria (ochronosis) defect and findings

Answer 25

Auto recess congenital deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate. Homogentisic acid accumulates in tissue –> pigment forming.
Sx: dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. May have debilitating arthralgias (HA toxic to cartilage).

Question 26

What three defects can lead to homocystinuria?

Answer 26

1) Cystathionine synthase deficiency (TX: dec met, inc cystine, b12, and folate in diet).
2) Dec affiinity of cystathione synthase for B6 (TX: Inc B6 and cysteine in diet)
3) Homocysteine methyltransferase/methionone synthase deficiency (tx: inc methionone in diet).

Question 27

Findings of homocystinuria?

Answer 27

Excess homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation (DOWN AND IN), thrombosis, and atherosclerosis (stroke/MI).

Question 28

Cystinuria defect

Answer 28

Auto recess hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of (COLA) cysteine, ornithine, lysine, and arginine.

Question 29

Cystinuria classic presentation

Answer 29

Recurrent precipitation of hexagonal cystine (2 cysteines connected by disulfide bond). Urinary cyanide-nitroprusside test is diagnostic. Tx: alkalinize urine (potassium citrate, acetazolamide) and chelating agents (penicillamine). Hydrate.

Question 30

What is the first step of ethanol metabolism?

Answer 30

Ethanol to acetaldehyde by Alcohol Dehydrogenase in cytosol.
Produces NADH.
Zero order kinetics.

Question 31

What is the second step of ethanol metabolism?

Answer 31

Acetaldehyde to Acetate by Acetaldehyde dehydrogenase to mitochondria.
Produces NADH.

Question 32

What does fomepizole do?

Answer 32

Inhibits alcohol dehydrogenase

Question 33

What is fomepizole used for?

Answer 33

methanol or ethylene glycol poisoning.

Question 34

What does disulfiram do?

Answer 34

Inhibits Acetaldehyde dehydrogenase

Question 35

What does disulfiram cause?

Answer 35

Acetaldehyde accumulates

Question 36

What is the limiting reagant for the metabolism of ethanol?

Answer 36

B3, NAD+

Question 37

What are the effects of increased NADH/NAD+ ratio in ethanol metabolism?

Answer 37

Pyruvate –> lactate (lactic acidosis)
Oxaloacetete –> malate (prevents gluconeogenesis, fasting hypoglycemia)
DHAP –> Glyc-3-P, which combines with fattys –> hepatosteatosis

Question 38

Why does ethanol metabolism favor ketogenesis?

Answer 38

Incr NADH disfavors TCA production of more NADH. Acetyl CoA goes to ketones and lipogenesis.