Protein and Amino Acid Metabolism

Question 1

What is Hartnup disease?

Answer 1

The defective transport of nonpolar or neutral amino acids. Leads to concentrated levels of these amino acids in the urine.

Symptoms: Extreme photosensitivity and failure to thrive

Question 2

What is Cystinuria?

Answer 2

Defective transport of cystine and dibasic amino acids Arg, Lys, and ornithine. Leads to kidney stones.

Question 3

List the 3 types of protein degradation.

Answer 3

Proteasome, lysosome, and autophagosome

Question 4

Describe lysosomal/autophagy

Answer 4

Contains more than 50 hydrolase-type intracellular proteolytic enzymes. Active at low pH (5). Non-selective.

Question 5

What are the 3 types of autophagy?

Answer 5

Macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)

Question 6

Describe proteasomal degradation.

Answer 6

Large proteasome cytoplasmic complexes than cleave polyubiquinated proteins.

Question 7

What is the inactive form of a protease called?

Answer 7

Zymogen

Question 8

How are proteolytic enzymes controlled?

Answer 8

They are secreted as needed in the form of zymogens, then activated by proteolytic cleavage.

Question 9

Describe how trypsin and chymotrypsin are activated.

Answer 9

The inactive forms (trypsinogen and chymotrypsinogen) are released into the SI lumen where trypsinogen is then activated by an enterokinase/enteropeptidase. Trypsin then activates chymotrypsinogen and other molecules of trypsinogen.

Question 10

What are the 3 main sources of the amino acid pool and how much comes from each source?

Answer 10

1. Body protein (protein turnover) = 400 g/day
2. Dietary protein = 100 g/day
3. De novo synthesis = variable, about 30 g/day average

Question 11

What is the difference between ketogenic and glucogeic amino acids?

Answer 11

Ketogenic AAs produce Acetyl CoA or acetoacetate, precursors for alpha keto acids, ketone bodies, and fatty acids.

Glucogenic AAs produce pyruvate or TCA cycle intermediates, precursors for glucose synthesis via glyconeogenesis.

Question 12

What is the ratio between ketogenic AAs, both ketogenic and glucogenic AAs, and glucogenic AAs?

Answer 12

2:5:13

Question 13

What is the required coenzyme of transaminases and what is it derived from?

Answer 13

Pyridoxyl-5’-phosphate (PLP). Derived from Vitamin B6.

Question 14

What are the clinically relevant transaminases and what are they used for?

Answer 14

Alanine transaminase (ALT) and aspartate transaminase (AST). Used to test for liver function.

Question 15

Describe homocystinuria.

Answer 15

Caused by a defect in PLP due to a Vitamin deficiencies (B6, B12, folic acid). Unable to fully metabolize methionine, leading to buildup for homocystine.

Symptoms: vision problems, bone deformities, limbs growing out of proportion, dementia, stroke, thrombosis

Question 16

Describe maple syrup urine disease.

Answer 16

Unable to fully metabolize branched-chain amino acids due to BCKD enzyme deficiency. Leads to BCAA build up in blood, causing a toxic effect on brain function.

Question 17

Describe phenylketonuria (PKU).

Answer 17

Caused by defect in phenylalanine hydroxylase (PAH) activity. Unable to metabolize Phe normally. Cannot drink diet sodas Supplement with Tyr to treat.

Symptoms: musty smelling odor, impairment of brain function

Question 18

What are the significant derivatives of Tryptophan?

Answer 18

Serotonin which also converts to melatonin. Serotonin levels can be used to detect carcinoid tumors.

Question 19

What are the significant derivatives of Tyrosine?

Answer 19

Thyroid hormones T3 and T4. Also produces melanin, where a deficiency can lead to albinism.

Question 20

What derivative of arginine can be used as a diagnostic test for MI?

Answer 20

Cardiac isoform creatine kinase (CK-MB)

Question 21

A defect in what enzyme leads to Albinism?

Answer 21

Tyrosinase

Question 22

What molecule is the precursor for both T3 and T4?

Answer 22

Thyroglobulin

Question 23

How is ammonia removed from the brain vs other tissues?

Answer 23

Removed as Glutamic acid and Glutamine in the brain. Removed as Glutamine and Alanine in other tissues. Products then brought to liver for use in Urea cycle.

Question 24

What is the rate-limited enzyme of the Urea cycle?

Answer 24

Carbamoyl phosphate synthetase 1

Question 25

What is the difference between ammonia and ammonium?

Answer 25

Ammonia (NH3) is the toxic agent as it is allowed to permeate membranes and cause a pH imbalance. Ammonium (NH4+) cannot permeate cell membranes.

Question 26

What is phosphocreatine synthesized from and what is it used for?

Answer 26

Synthesized from Arg, Gly, and Met. Used as a storage form of energy in muscle, brain, and sperm.

Question 27

What is an elevated creatinine indicative of?

Answer 27

Kidney dysfunction