N metabolism and protein turnover

Question 1

Is ammonia a neurotoxin?

Answer 1

yes

Question 2

What percentage of the amino acids leaving the gut and liver are BCAA?

Answer 2

25%, 60%

Question 3

What are the BCAA

Answer 3

branch-chain amino acids: leucine, valine, isoleucine

Question 4

Where do amino acids go in the Fed state?

Answer 4

absorbed from the gut, they go to the liver for metabolism into other substances (VLDL/Chylomicrons/glycogen) before going into the blood to other cells

Question 5

Where do amino acids go in the Fasting state?

Answer 5

glutamine, alanine and other AA from skeletal muscle go to the kidney for extraction of NH4, conversion to serine and alanine, then to the liver. glutamine also converted to alanine in the gut before going to the liver.

Question 6

What two amino acids are Nitrogen carriers?

Answer 6

Glutamine and Alanine

Question 7

How do the kidneys support liver gluconeogenesis during fasting?

Answer 7

The convert glutamine to alanine via transaminases. Alanine is a precursor to pyruvate, which can undergo gluconeogenesis.

Question 8

How doe glutamine enter the TCA cycle?

Answer 8

deamidation to glutamate, deamination to a-ketoglutarate

Question 9

What amino acid buffers hydrogen ions?

Answer 9

glutamine (as a source of ammonia)

Question 10

What amino acid is the primary fuel for the kidneys in normal and fasting states?

Answer 10

glutamine

Question 11

What type of energy is used by cells of the renal medulla?

Answer 11

glucose

Question 12

What type of energy is used by cells of the renal cortex?

Answer 12

Lactate

Question 13

What is the major fuel of the gut?

Answer 13

glutamine

Question 14

What three things does the gut use for fuel/oxidation?

Answer 14

glutamine (major), BCAA and aspartate

Question 15

What uses up short-chain fatty acids?

Answer 15

bacteria in the colon

Question 16

Amino acids that produce pyruvate or Krebs cycle intermediates are called:

Answer 16

glucogenic AAs

Question 17

Amino acids that produce acetyl CoA or acetoacetyl CoA are called:

Answer 17

ketogenic AAs

Question 18

What two amino acids are purely ketogenic?

Answer 18

leucine and lysine

Question 19

What five amino acids are both ketogenic and glucogenic?

Answer 19

tryptophan, phenylalanine, tyrosine (aromatics), isoleucine, threonine

Question 20

What enzyme oxidizes the BCAA? What is the reaction type and what are the cofactors?

Answer 20

branched-chain keto-acid dehydrogenase. oxidative decarboxylation. cofactors: lipoic acid, CoA, TPP, NADH, FADH2

Question 21

Of the 5 cofactors for the branched-chain keto-acid dehydrogenase enzyme, which is NOT a vitamin derivative?

Answer 21

lipoic acid

Question 22

What are the two steps for BCAA degradation?

Answer 22

BCAA specific aminotransferase converts them to branched chain keto-acids which then undergo oxidative decarboxylation.

Question 23

What is the cause for maple syrup urine disease?

Answer 23

a defective branched-chain keto-acid dehydrogenase

Question 24

What percentage of muscle amino acid content is BCAA?

Answer 24

25%

Question 25

What does muscle do with BCAA?

Answer 25

uses them for fuel, then converts them to alanine and glutamine to transfer N to other tissues.

Question 26

What is the primary fuel for muscles?

Answer 26

BCAA

Question 27

Is tyrosine an essential Amino acid? why/why not?

Answer 27

Tyrosine is NOT an essential amino acid because it can be made from phenylalanine via phenylalanine hydroxylase.

Question 28

What enzyme converts phenylalanine to tyrosine? what is its cofactor?

Answer 28

phenylalanine hydroxylase. cofactor: tetrahydrobiopterin

Question 29

What condition occurs when one cannot convert phenylalanine to tyrosine? What are 3 toxic by-products that can accumulate?

Answer 29

phenylketonuria. phenylpyryvate, phenyllactate, phenylacetate can accumulate

Question 30

What is classical PKU?

Answer 30

A defect in the phenylalanine hydroxylase enzyme that can be treated by a phenylalanine-restricted diet

Question 31

What is atypical PKU?

Answer 31

A defect in tetrahydrobiopterin reductase enzyme

Question 32

What two substances doe tyrosine eventually get catabolized to?

Answer 32

fumarate and acetoacetate

Question 33

Which substance is catabolic in nature, which is anabolic? Insulin or glucagon?

Answer 33

insulin is anabolic, glucagon in catabolic

Question 34

What differences are there between a high-carbohydrate meal versus a high-protein meal to insulin/glucagon levels?

Answer 34

a high protein diet stimulates both catabolism and anabolism, whereas a high carbohydrate diet stimulates only anabolism. Also, a the stimulation of anabolism is short-lived and drops rapidly in a high-carb meal.

Question 35

What two amino acids are the primary regulators of glucagon release?

Answer 35

arginine and leucine

Question 36

What is a negative nitrogen balance? give an example

Answer 36

N excretion higher than consumption- eg. a sick person not eating well

Question 37

What is a positive nitrogen balance? give an example

Answer 37

N excretion lower than consumption- eg. newborns using AA for growth

Question 38

What six things characterize a hypercatabolic state?

Answer 38

increased fuel metabolism and a negative nitrogen balance. degradation of skeletal muscle protein. increased synthesis of immune system components and gluconeogenesis. increased urea synthesis.

Question 39

How does insulin stimulate cholesterol uptake into cells?

Answer 39

by stimulating lipoprotein lipase

Question 40

What are the ten essential amino acids?

Answer 40

PVT TIM HALL : phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine

Question 41

How is alanine synthesized?

Answer 41

transamination from pyruvate

Question 42

How is aspartate synthesized?

Answer 42

transamination of oxaloacetate

Question 43

How is asparagine synthesized?

Answer 43

amidation of aspartate

Question 44

How is glutamate synthesized?

Answer 44

glutamate dehydrogenase, a reductive amination of a-keto glutarate

Question 45

How is glutamine synthesized?

Answer 45

amidation of glutamate

Question 46

How is arginine synthesized?

Answer 46

from the urea cycle

Question 47

How is proline synthesized?

Answer 47

from glutamate

Question 48

how is serine synthesized?

Answer 48

from 3-phosphoglycerate (glycolysis)

Question 49

how is glycine synthesized?

Answer 49

from serine

Question 50

how is cystein synthesized?

Answer 50

from serine and methionine (sulfur-containing)

Question 51

how is tyrosine synthesized?

Answer 51

from phenylalanine

Question 52

What two things does and enzyme need to synthesize a reaction to form a non-essential amino acid?

Answer 52

a precursor and an amine group (from a N-donor)

Question 53

What are the three one-carbon carriers and what type of carbons do they carry?

Answer 53

biotin (CO2); tetrahydrofolate (THF) (one-carbon units in all oxidation states except CO2); S-adenosylmethionine (active methyl group donor)

Question 54

What three reactions does biotin mediate?

Answer 54

pyruvate carboxylase (in gluconeogenesis); carbonyl CoA rxns; odd-chain FA degradation

Question 55

What is SAM?

Answer 55

a ribose sugar nucleotide

Question 56

What is vitamin B9?

Answer 56

folate

Question 57

Why is folate a vitamin?

Answer 57

Because we cant synthesize the pteridine ring

Question 58

How is folic acid absorbed in the gut?

Answer 58

reductases and conjugases on the brush border deconjugate the THF from polyglutamates. THF is absorbed, then reconjugated intracellularly

Question 59

What is the most reduced form of THF and why is it unique?

Answer 59

5-methyl-FH4, it's formation is irreversible, so it cannot form any other C oxidation states. Other forms of THF are interconvertible.

Question 60

What is the major one-carbon source, and what are three other one-carbon sources in folate derivatives?

Answer 60

serine is the major source. glycine, histidine and formate are other sources

Question 61

Which amino acid is an immediate precursor to SAM

Answer 61

methionine

Question 62

After SAM loses a carbon group, what does it become?

Answer 62

SAH

Question 63

After SAH loses Adenosine, what does it become?

Answer 63

Homocysteine

Question 64

How does homocysteine regenerate methionine? name the enzyme and two cofactors

Answer 64

homocysteine methyltransferase. requires B12 and an activated methyl from N-methylTHF.

Question 65

What two steps (name enzyme and cofactor) are required to convert homocysteine to cysteine?

Answer 65

1. cystathionine synthase (req. pyridoxal phosphate) | 2. cystathionase (req. pyridoxal phosphate)

Question 66

What is the methyl trap hypothesis?

Answer 66

inadequate B12 traps the THF methyl group from converting homocysteine to methionine. Thus no SAM is made, contributing to macrocytic anemias.

Question 67

What are five products that SAM can help produce?

Answer 67

epinephrine, creatine, methylated nucleotides, phosphatidylcholine, melatonin

Question 68

What four amino acids can be degraded to succinyl CoA?

Answer 68

valine, methionine, isoleucine, threonine

Question 69

Conversion of propionyl CoA to methylmalonyl CoA requires what vitamin cofactor?

Answer 69

biotin

Question 70

What are two reactions that require B12?

Answer 70

conversion on homocysteine to methionine; conversion on methylmalonyl CoA to Succinyl CoA

Question 71

What 2 compounds would accumulate in a B12 deficiency?

Answer 71

homocysteine (less so, as it can be converted to cysteine) and methylmalonyl CoA

Question 72

What two things in the gut are required for B12 absorption?

Answer 72

R-binders and intrinsic factor released from parietal cells

Question 73

Where is B12 absorbed in the gut?

Answer 73

the ileum

Question 74

What happens in methylmalonic aciduria?

Answer 74

defect of the methylmalonyl CoA reductase that normally converts methylmalonyl CoA to succinyl CoA. May respond to high dose of B12

Question 75

If B12 absorption is impaired, why might high doses of B12 help?

Answer 75

1% can passively diffuse through the small intestine