AA Metabolism

Question 1

what is a positive nitrogen balance?

Answer 1

nitrogen intake exceeds excretion

Question 2

who would have a positive nitrogen balance?

Answer 2

babies, burn victims trying to repair, people who are growing

Question 3

what is negative nitrogen balance?

Answer 3

nitrogen excretion exceeds intake, see this in essential amino acid deficiency

Question 4

how many AA cannot be synthesized by the human body, and what happens if they are not taken in by the diet?

Answer 4

9 AA are essential, meaning they cannot be synthesized by the body. if don’t have all 20 AA or if it can’t be done quick enough, cannot do protein biosynthesis, and we excrete more N than normal.

Question 5

what does glucogenic/glycogenic AA mean?

Answer 5

some amino acids ONLY go on to make pyruvate or intermediates of the TCA cycle, that can go on to make glucose in the liver

Question 6

what does ketogenic AA mean??

Answer 6

some amino acids ONLY go on to make acetyl coa or ketone bodies

Question 7

what amino acid is ONLY ketogenic?

Answer 7

leucine

Question 8

what is special in the proximal convoluted tubules regarding AA transport?

Answer 8

the special AA transporter that is in the intestinal epithelium is also in the proximal tubules in the kidney. it is used to reabsorb cystine, homocystine, lysine, ornithine, or arginine.

Question 9

what is cystine?

Answer 9

cysteine hooked together with sulfhydryl cross link - is not very soluble in urine, so you want to reabsorb it to the blood to prevent kidney stones

Question 10

what happens in cystinuria?

Answer 10

if the special cystine transporter in the PCT is not working, it cannot reabsorb cystine, homocystine, lysine, arginine, or ornithine into the blood, therefore, increased kidney stones.

Question 11

diagnosis of cystinuria?

Answer 11

take urine and assay of kidney stone for lysine, arginine, ornithine in higher concentrations than normal.

Question 12

how are branched chain amino acids taken up into the cells?

Answer 12

1. in the muscle, they must be transaminated to their alpha keto acids (are branched alpha keto acids) because they are insoluble. 2. they are transported as their alpha keto acids to the liver. 3. liver oxidatively decarboxylates them by oxidative decarboxylation dehydrogenase (alpha ketoacid dehydrogenase) 4. then can undergo further degradation and handling to their respective gluconeogenic or ketogenic worlds

Question 13

what enzyme is in the liver that decarboxylates alpha keto acids derived from branched chain AA?

Answer 13

oxidative decarboxylation dehydrogenase/alpha ketoacid dehydrogenase

Question 14

what occurs if alpha ketoacid dehydrogenase is deficient?

Answer 14

problem in the liver - branched chain alpha keto acids accumulate in the blood and urine - maple syrup urine disease - AA don’t accumulate in the blood, bc muscle has transaminated them to their branched chain alpha ketoacids

Question 15

symptoms of maple syrup urine disease

Answer 15

1.maple syrup odor of urine 2. mental retardation (bc branched chain alpha ketoacids cross BBB) 3. abnormal muscle tone 4. ketosis (bc branched chain alpha ketoacids) 5. coma 6. death

Question 16

describe phenylalanine and tyrosine metabolism

Answer 16

1. phenylalanine —> tyrosine via phenylalanine hydroxylase/BH4 2. later in the pathway, homogentisate —->—>fumarate and acetoacetate via homogentisate oxidase

Question 17

where does phenylalanine breakdown occur?

Answer 17

in stomach via phenylalanine hydroxylase, which requires tetrahydrobiopterin (BH4)

Question 18

pathology of phenylketonuria (PKU)

Answer 18

1. phenylalanine hydroxylase is deficient, so phenylalanine is not converted to tyrosine 2. phenylalanine builds up and leads to transamination into phenylpyruvate 3. phenylpyruvate spontaneously loses CO2 and becomes phenylacetate, or is reduced to phenyllactate 4. phenylacetate and phenyllactate build up in the blood, leading to phenylketonuria

Question 19

symptoms of PKU

Answer 19

1. mental retardation 2. microcephaly 3. musty odor

Question 20

treatment of PKU

Answer 20

1. diet low in Phe 2. avoid aspartame (is a tripeptide with Phe in it, so when degraded, becomes Phe) 3. have a good diet during pregnancy

Question 21

what is alkaptonuria?

Answer 21

part of phe and tyrosine metabolism: homogentisate oxidase is deficient, so homogentisate cannot go to fumarate or acetoacetate. homogentisic acid builds up.

Question 22

what is the triad of alkaptonuria?

Answer 22

1. dark urine - see in childhood 2. ochronosis - see later in life (homogentisate builds up in joints) 3. arthritis - see later in life (homogentisate builds up in joints)

Question 23

what is the propionic acid pathway of vomit?

Answer 23

Valine or Methionine Isoleucine Threonine

Question 24

describe normal metabolism of methionine

Answer 24

1. S-adenosyl methionine (SAM) pulls off a methyl from methionine to become S-adenosylhomocysteine
2. SAH becomes homocysteine
3. homocysteine becomes cystathionine via cystathionine synthase and PLP/B6
4. cystathionine becomes alpha ketobutyrate and cysteine via cystathionine lyase and PLP/B6
5. alpha ketoglutarate becomes propionyl CoA
6. propionyl CoA becomes D-methylmalonyl CoA via biotin
7. D-methylmalonyl CoA becomes L-methylmalonyl CoA
8. L-methylmalonyl CoA becomes succinyl CoA via B12
9. succinyl CoA goes to TCA cycle

Question 25

describe the conversion of homocysteine to methionine

Answer 25

methyl-tetrahydrofolate donates its methyl group to B12, which works as a cofactor for homocysteine methyltransferase to transfer a methyl to homocysteine to make methionine

Question 26

which 2 reactions in the body use B12?

Answer 26

1. homocysteine methyltransferase
2. conversion of L-methylmalonyl CoA to succinyl CoA

Question 27

what 4 pathologies could cause homocystinuria?

Answer 27

1. genetic deficiency of homocysteine methyltransferase or cystathionine synthase
2. B12 deficiency
3. folate deficiency
4. B6 deficiency

Question 28

describe how B12 deficiency could cause homocysteinuria

Answer 28

B12 is needed to transfer the methyl group from methyltetrahydrofolate to homocysteine methyltransferase, so without this, homocysteine could not be converted to methionine.

Also, without B12, L-methylmalonyl CoA could not be converted to succinyl CoA.

Question 29

what would you expect to see if homocysteinuria was caused by vitamin B12 deficiency?

Answer 29

increase in homocysteine

increase in methylmalonic acid (methylmalonic acidurea)

megaloblastic anemia

Question 30

what would you expect to see if homocysteinuria was caused by B6 deficiency?

Answer 30

homocysteinuria

problems with transamination - urea cycle

megaloblastic anemia

Question 31

what would you expect to see if homocysteinuria was caused by folic acid deficiency?

Answer 31

homocysteinuria

problems with DNA synthesis - purine synthesis decreases, cannot make dTMP (thymine)

megaloblstic anemia

Question 32

symptoms of homocysteinuria

Answer 32

1. dislocated lens
2. deep vein thrombosis - blood coagulation proteins messed up by increased homocysteine
3. stroke - coag problem
4. atherosclerosis - coag problem
5. mental retardation - free sulfhydryl group makes sulfhydryl crosslinks, makes and breaks rapidly, changes shape and function of the protein

Question 33