Protein and Amino Acid Metabolism Flashcards
What is Hartnup disease?
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
What is Cystinuria?
Defective transport of cystine and dibasic amino acids Arg, Lys, and ornithine. Leads to kidney stones.
List the 3 types of protein degradation.
Proteasome, lysosome, and autophagosome
Describe lysosomal/autophagy
Contains more than 50 hydrolase-type intracellular proteolytic enzymes. Active at low pH (5). Non-selective.
What are the 3 types of autophagy?
Macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA)
Describe proteasomal degradation.
Large proteasome cytoplasmic complexes than cleave polyubiquinated proteins.
What is the inactive form of a protease called?
Zymogen
How are proteolytic enzymes controlled?
They are secreted as needed in the form of zymogens, then activated by proteolytic cleavage.
Describe how trypsin and chymotrypsin are activated.
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.
What are the 3 main sources of the amino acid pool and how much comes from each source?
- Body protein (protein turnover) = 400 g/day
- Dietary protein = 100 g/day
- De novo synthesis = variable, about 30 g/day average
What is the difference between ketogenic and glucogeic amino acids?
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.
What is the ratio between ketogenic AAs, both ketogenic and glucogenic AAs, and glucogenic AAs?
2:5:13
What is the required coenzyme of transaminases and what is it derived from?
Pyridoxyl-5’-phosphate (PLP). Derived from Vitamin B6.
What are the clinically relevant transaminases and what are they used for?
Alanine transaminase (ALT) and aspartate transaminase (AST). Used to test for liver function.
Describe homocystinuria.
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
Describe maple syrup urine disease.
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.
Describe phenylketonuria (PKU).
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
What are the significant derivatives of Tryptophan?
Serotonin which also converts to melatonin. Serotonin levels can be used to detect carcinoid tumors.
What are the significant derivatives of Tyrosine?
Thyroid hormones T3 and T4. Also produces melanin, where a deficiency can lead to albinism.
What derivative of arginine can be used as a diagnostic test for MI?
Cardiac isoform creatine kinase (CK-MB)
A defect in what enzyme leads to Albinism?
Tyrosinase
What molecule is the precursor for both T3 and T4?
Thyroglobulin
How is ammonia removed from the brain vs other tissues?
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.
What is the rate-limited enzyme of the Urea cycle?
Carbamoyl phosphate synthetase 1
What is the difference between ammonia and ammonium?
Ammonia (NH3) is the toxic agent as it is allowed to permeate membranes and cause a pH imbalance. Ammonium (NH4+) cannot permeate cell membranes.
What is phosphocreatine synthesized from and what is it used for?
Synthesized from Arg, Gly, and Met. Used as a storage form of energy in muscle, brain, and sperm.
What is an elevated creatinine indicative of?
Kidney dysfunction
