Biochem Lecture 29 (Nitrogen)

Question 2

Big picture: what happens to excess amino acids after we digest them?

Answer 2

Not stored; go to gluconeogenesis and/or lopgenesis. Excess N disposed over as urea and (some) NH3.

Question 3

What are the sources of a.a.’s?

Answer 3

diet, synthesis (of NON-essential aa’s), and protein degradation

Question 4

What are the essential a.a.’s?

Answer 4

Phe, Met, Trp, Lys, Thr, His, Leu, Ile, Val

Question 5

How are a.a.’s digested?

Answer 5

peptidases on intestinal cells: prot_>tri- & di-peptides; absorbed via Na+ symport

Question 6

Compare amt. a.a.’s from diet vs. from protein turn-over

Answer 6

synth and degradation of protein (protein turnover) utilizes and returns to the free amino acid pools an amount of amino acids one order of magnitude greater than those provided in the diet

Question 7

What are the two prot. Degrad. Paths and how do they differ in f(x)?

Answer 7

ubiquination_>proteasome; lysosomal (a.k.a. autophagy); ubiq targets specific prots vs. lysosomal is bulk (e.g. for a mito)

Question 8

How does the ubiquination pathway work?

Answer 8

in cytosol: ubiq attached to lysine residues, proteasome recog’s it shreds prot into small peptides; other proteases break these down into a.a.’s

Question 9

How is autophagy regulated (broadly speaking)?

Answer 9

insulin inhibits autophagy; starvation/a.a. deficiency activates it

Question 10

Why is autophagy esp. important for neonates?

Answer 10

Mother’s milk is devoid of calories at first; need to produce calories

Question 11

What are some regulators of prot synth?

Answer 11

When there is ample a.a.’s eIF4 (initiation factor) upregulates translation via: [insulin & a.a.’s]_>P’s 4E-BP1_>releases active form of eIF4; When there is STARVATION, eIF2 is sequestered via P’ation

Question 12

Before a.a’s can be broken down to be used for lipogenesis or gluconeogenesis, the amino group must be removed. What two fates does it then have?

Answer 12

Aminotransferase reactions and Oxidative deamination

Question 13

Describe the basic transaminase rxn

Answer 13

Aminotransferases transfers amino group from a.a. to a-KG forming glutamate; an a-keto acid is formed, too, which is what can jump into the Citric Acid cycle, etc.

Question 14

What co-factor do transaminases require?

Answer 14

pyridoxal phosphate (a.k.a. PLP; a derivative of Vitamin B6)

Question 15

Describe the ALT/AST reactions.

Answer 15

ALT: alanine + αKG —> pyruvate + glutamate

AST: aspartate + αKG—> oxaloacetate + glutamate

Bolded products to TCA

Question 16

How does one get rid of all the glutamate produced by aminotransferases?

Answer 16

urea cycle via the enzyme glutamate DH

Question 17

How does glutamate DH work? (Describe the rxn.)

Answer 17

glutamate is oxidized and deaminated to produce NH3 and a-KG

Question 18

What becomes of the urea made by glutamate DH?

Answer 18

The majority is converted to urea in the liver via the urea cycle.

small amount excreted in urine via renal glutaminase:

glutamine —> glutamate and NH4

Question 19

Alkaptonuria

Answer 19

deficiency in homogentisate oxidase, (enzyme in pathway for degradation of tyrosine)

homogentisate accumulates and is largely excreted in urine. Homogentisate produces dark pigments upon oxidation, which is apparent in the patient’s urine

also deposited in joints over time and can lead to severe arthritis

Question 20

Maple syrup urine disease (MSUD)

Answer 20

Maple syrup urine disease (MSUD) - deficiency in branched-chain α-keto acid dehydrogenase (Mito enzyme similar to pyruvate dehydrogenase)

causes leucine, isoleucine, valine and their keto-acids to accumulate.

Disease causes neurological deficits, imparts an odor of maple syrup in patient

Answer 21

• deficiency in cystathionine synthase, homocystine elevated, neurological deficits, cardiovascular disease

Question 22

Phenylketonuria (PKU)

Answer 22

deficiency in phenylalanine metabolism, neurological deficits,