Protein/AA Metabolism

Question 1

Exopeptidase

Answer 1

Attacks C- termini and N- termini of polypeptides/proteins.

Carboxypeptidase and aminopeptidase, respectively

Question 2

Endopeptidase

Answer 2

Attacks within the protein at specific site (digests internal peptide bonds)

Question 3

Lysosomes in proteolytic control

Answer 3

Intracellular proteolytic control - low pH in lysozyme and contain many proteolytic enzymes

Non-selective protein degradation:

• macroautophagy (many proteins in an endosome taken up)
• microautophagy (one protein take up at a time)
• chaperone-mediated autophagy (CMA)

Question 4

Proteosome structure

Answer 4

19S regulatory (capping) units on either side of a 20S catalytic core unit that degrades the ubiquitinylated protein

Question 5

Zymogen example

Answer 5

Inactive: Trypsinogen and chymotrypsin released into SI lumen

Active: Trypsinogen activated by enzyme enterokinase
-Active Trypsin activates chymotrypsinogen

Question 6

Ketogenic amino acids

Answer 6

Leucine and Lysine (the L’s)

Question 7

Ketogenic AND Glucogenic AAs

Answer 7

Phe, Ile, Thr, Tyr, Trp

Mnemonic: brad PITTT

Question 8

Ketogenic AAs

Answer 8

Can act as precursors for alpha keto acids, ketone bodies and fatty acids

Question 9

Glucogenic AAs

Answer 9

Can act as precursors for glucose synthesis via gluconeogenesis

Question 10

Transamination

Answer 10

Shuffling of amine groups

Amino group transferred to alpha-ketoacid

Enzymes called: transaminase/aminotrasnferases - Requires PLP from Vitamin B6 (Pyridoxyl)

Question 11

ALT

Answer 11

Alanine Aminotransferase

Pyruvate + GLUTAMATE ALANINE + alpha-ketoglutarate

Question 12

AST

Answer 12

Aspartate Aminotransferase

Oxaloacetate + GLUTAMATE ASPARTATE + a-ketoglutarate

Question 13

Succinyl-CoA amino acid precursors

Answer 13

Met, Val, Ile

Question 14

Homocystinuria / Hyperhomocystemia

Answer 14

In the metabolism of Methionine, and intermediate homocysteine is formed.

Cystathionine synthase metabolizes homocysteine further with PLP.

 - When enzyme is defective OR vitamin deficiency (B6, B12, folic acid), homocysteine builds up
 - homocysteine dimerizes with itself to form homocystine = TOXIC

Homocystine accumulation = homocystinuria / hyperhomocystemia

Question 15

Homocystinuria affected organs

Answer 15

Eye
Skeletal
CNS
Vascular

Question 16

Branched Amino Acids

Answer 16

Ile, Leu, Val

Question 17

Maple Syrup Urine Disase (MSUD)

Answer 17

Autosomal disease resulting from branched-chain alph-keto acid dehydrogenase complex (BCKD) deficiency.
—-> Branched-chain ketoaciduria

• branched-chain AAs present in urine = maple syrup odor
• branched-chain AA accumulate in blood = toxic effect —> mental retardation

Treatment: synthetic diet limiting Val, Ile, Leu

Question 18

Phenylketonuria (PKU)

Answer 18

PKU caused by defects in Phenylalanine Hydroxylase. Disrupts metabolism of Phe.

Or caused by tetrahydrobiopterin deficiency

Build-up of Phe forms Phenyllactate and Phenylacetate

Question 19

Phenyllactate and Phenylacetate

Answer 19

Formed from build-up of Phe due to defective Phenylalanine Hydroxylase

Disrupts neurotransmission and blocks AA transport in brain

Phenyllactate causes musty odor in urine

Question 20

Tetrahydrobiopterin

Answer 20

Cofactor of Phenylalanine Hydroxylase. Deficiency in tetrahydrobiopterin results in Phenylalanine build-up —> PKU

Question 21

Tryptophan derivatives

Answer 21

Trp —> Serotonin —> Melatonin (sleep)

Trp —>Niacin —> NAD(P)

*BOTH require Vitamin B6 - Pyrodoxal

Question 22

Tyrosine Derivatives

Answer 22

Tyr —> Dopamine —> Norephinephrine —> Epinephrine

Tyr —> Thyroid hormones (T3 / T4)

Tyr—> Melanin (pigments)

Question 23

Serine Derivative

Answer 23

Acetylcholine

Question 24

Albinism

Answer 24

Due to a severe lack of melanin

Conversion of Tyrosine —> melanin is blocked by defective enzyme

Complete absence of pigmentation in the skin, hair and eyes

Question 25

Thyroglobulin

Answer 25

Protein made by the thyroid used to produce T3 and T4 hormones
-Some of its tyrosine residues can be iodinated to produce T3 and T4

Hyperthyroidism patients treated with agents that block iodination of Tyr residues —> Decreased production of T4 and T3

Question 26

AA used in removal of nitrogen

Answer 26

Brain: Glu, Gln

Other tissue: Gln, Ala

Connects to urea cycle for excretion from the body

Question 27

Ammonia Toxicity

Answer 27

Excessive ammonia due to disorders in the urea cycle - can have highly toxic effects on brain/CNS
- cerebral edema or intracranial hypertension

NH3 can permeate membranes —> Toxic

NH3 causes pH imbalance

Question 28

Urea cycle relation to high protein diet

Answer 28

High protein diet increases urea production (due to large nitrogen intake).

- 20-30% of our urea is hydrolyzed in the GI tract by bacteria, providing a source of nitrogen salvage for gut bacteria
- High protein diet enhances production of urea as well as gut bacteria hydrolysis of urea

Question 29

Creatine

Answer 29

Creatine made from Arg, Gly, Met

Question 30

Phosphocreatine (creatine phosphate)

Answer 30

Serves as a storage form of energy in muscle, brain and sperm. It can quickly generate ATP

Question 31

Creatinine

Answer 31

Small amount of creatinine phosphate non-enzymatically converted to creatinine.

- excreted in urine
- Great marker to check in serum levels to indicate any kidney dysfunction or muscle degeneration