Amino Acid and Protein

Question 1

How many grams of protein are produced in a day for body protein?

Answer 1

400 g/day in body protein
~100 g/day dietary protein
synthesized nonessential amino acids

Question 2

Essential Amino Acids

Answer 2

Methionine, Threonine, Valine, Phenylalanine, Isoleucine, Tryptophan, Lysine, Leucine

Question 3

Aromatic AA synthesis

Answer 3

Phe –> Tyrosine via phenylalanine hydroxylase

Ribose-5-P –> His

Question 4

Serine AA synthesis

Answer 4

3-Phosphoglycerate –> Ser –> Cys/Gly

Question 5

Pyruvate AA synthesis

Answer 5

Pyruvate –> alanine

Question 6

Aspartate AA synthesis

Answer 6

Oxaloacetate –> Asp –> Asn

Question 7

Glutamate AA synthesis

Answer 7

A-Ketoglutarate –> Glu –> Gln, Pro, Arg

Question 8

Intracellular proteolytic control

Answer 8

Lysosomal/autophagy
- lysosomes sequester >50 hydrolase-type intracellular proteolytic enzymes
cleave polyubiquitin pathway

Question 9

Ketogenic AA

Answer 9

Precursors for alpha keto acids, ketone bodies, and fatty acids , KL

Question 10

Ketogenic and Glucogenic AA

Answer 10

PITTT

Question 11

Glucogenic AA

Answer 11

Precursors for glucose synthesis via gluconeogenesis (13)

Question 12

alpha-ketoglutarate is a product of what AAs?

Answer 12

Gln, His, Arg, Pro, Glu

Question 13

Succinyl CoA is a product of what AAs?

Answer 13

Ile, Val, Met, Thr

Question 14

Fumarate is a product of what AAs?

Answer 14

Phe, Tyr

Question 15

Oxaloacetate is a product of what AAs?

Answer 15

Asn, Asp

Question 16

Pyruvate is a product of what AAs?

Answer 16

Thr, Gly, Trp, Ser, Ala, Cys

Question 17

What are transaminase reactions and what are required?

Answer 17

Shuffling of amine groups
1. amino group is transferred to an alpha-ketoacid
2. coupled reactions
3. enzymes called transaminases/aminotransferases
require pyridoxyl-5’-phosphate (PLP) derivative of Vitamin B6

Question 18

hyperhomocysteinemia and homocystinuria

Answer 18

vitamin deficiencies of B6 (PLP, pyrioxidine), B12 (cobalamine), and folic acid (B9), or genetic defects in enzymes cystathionine B-synthase can cause defective metabolism of homocysteine

Question 19

Phenylketonuria

Answer 19

defects in the activity of phenylalanine hydroxylase (PAH)
-most common IEM
-phe converted to phenylpyruvate to phenyllactate (musty urine) to phenylacetate
-Disrupts neurotransmission and block amino acid transport in the brain as well as myelin formation, resulting in severe brain function
Secondary PKU resulting from tetrahydrobiopterin deficiency - defects in synthesis or regeneration of BH4

Question 20

Tryptophan derivatives

Answer 20

Serotonin –> melatonin
Niacin –> NAD(P)
Needs B6

Question 21

Ser derivatives

Answer 21

Acetylcholine

Question 22

Glu derivatives

Answer 22

GABA

Question 23

Tyrosine derivatives

Answer 23

Dopamine –> NEpi –> Epi
thyroid hormones T3+ T4 (hyperthyroidism)
melanin

Question 24

Thyroglobulin and thyroid hormone

Answer 24

Thyroglobulin is a 660 kDa protein made by thyroid and is used to produce T4 and T3
-Thyroglobulin has ~120 tyr residues, some of which can be labeled with iodine (mono- and diiodinated Tyr)
-T4 is the combination of 2 diiondinated Tyr
-T3 is the combination of 1 mono and 1 diiodinated Tyr; more potent than T4 but with shorter half-life
patients are treated with hyperthyroidism are treated with agents which block iodination of thyroglobulin to decrease the production of T4 and T3

Question 25

Urea cycle and high protein diet

Answer 25

urea production is increased by a high protein diet and decreased by high carb diet

• insulin and glucagon play a role in urea production
• about 20-30 %of urea produced is hydrolyzed in the GI tract by bacterial urease
• provides a source of ammonia nitrogen for gut bacteria, salvage and reuse
• high protein diet enhances this production and hydrolysis

Question 26

How is nitrogen removed in the brain?

Answer 26

Removed as Glutamine and Glutamic acid via glutamine synthesis
brain likes the g’s….(think glucose)

Question 27

How is nitrogen removed in other tissues?

Answer 27

Removed as Glutamine and alanine

Question 28

How does the brain remove excess NH4?

Answer 28

creates glutamine and glutamate via transamidation processes
alpha-ketoglutarate (-NADPH) –> glutamate(-ATP) –> glutamine –> (liver)
needs NADPH and ATP

Question 29

How does the muscle remove excess NH4?

Answer 29

Makes takes glutamate and adds the NH2 group to pyruvate via ALT to make alanine
alanine can then be shuttled to the liver to make glucose via gluconeogenesis

pyruvate +Glu –> Alanine + alpha-keto

Question 30

Alanine aminotransferases (ALT)

Answer 30

Pyruvate + glutamate –> alanine + alpha-ketoglutarate

Question 31

Aspartate aminotransferases (AST)

Answer 31

OAA + glutamate –> aspartate + alpha-ketoglutarate

Question 32

Glutamine aminohydrolase (GA)

Answer 32

glutamine + H2O –> glutamate + NH3

Question 33

Arginine derivatives

Answer 33

MRG (margaritas) Met, Arginine, Glycine
converted to Creatine Phosphotase (energy for muscle, brain, sperm)…immediate energy source
Cardiac isoform creatine kinase (CK-MB) diagnostic for MI

Question 34

Rate Limiting step in urea cycle and where does it take place

Answer 34

NH4+ (bicarb, 2ATP) –> carbamoyl phosphate by CPSI (carbamoyl phosphate synthetase I) IN THE MITOCHONDRIA

Question 35

Hyperammonemia

Answer 35

Autosomal recessive disorder
Defect: carbamoyl phosphate synthetase I
Issue: overproduction of NH3+ can cause brain damage and CNS because it can easily pass the BBB.. cerebral edema
disrupts TCA cylce (glutamine synthesis from pos feedback)

Question 36

What substances when elevated in the serum indicates kidney dysfunction and muscle degeneration?

Answer 36

Creatinine (ring form of creatine which is derived from MRG)