Lect 8 Protein & AA Metabolism Flashcards
Amino Acid Pool is population of free AAs that is supplied by _ ? Depleted by _ ?
- Protein Turnover, Digested Food (essential AAs) , and De Novo Synthesis (nonessential AAs)
- Production of protein, Nitrogen containing compound synthesis, Degradation
Proteolysis is _
Degradation of proteins for reabsorption
Exopeptidase
attacks C- (carboxypeptidase) or N-terminus (aminopeptidase) ends
Endopeptidase
attacks within protein at specific site (digests internal peptide bonds)
What pH are proteases active in Lysosomal Degradation/Autophagy? Inactive?
Proteases active at acidic pH of lysosome (5), inactive at pH of cytoplasm (7)
How does intracellular proteolytic control work?
Proteolytic enzymes controlled through “marking” mechanisms tagging protein substrate for degradation
How does proteasomal degradation work?
Large proteasome cytoplasmic complexes cleave polyubiquinated proteins
What is the Extracellular Proteolytic Control mechanism?
Proteolytic enzymes secreted as needed (inactive zymogens activated by proteolytic cleavage)
Essential AA
PVT TIM HALL
- Phenylalanine (Phe)
- Valine (Val)
- Threonine (Thr)
- Tryptophan (Trp)
- Isoleucine (Ile)
- Methionine (Met)
- Histidine (His)
- Arginine (Arg)
- Leucine (Leu)
- Lysine (Lys)
- Glutamine (Gln)
Nonessential AA
- Alanine (Ala)
- Aspartate (Asp)
- Asparagine (Asn)
- Cysteine (Cys)
- Glutamate (Glu)
- Gultamine (Gln)
- Glycine (Gly)
- Proline (Pro)
- Serine (Ser)
- Tyrosine (Tyr)
Ketongenic AAs
2
Leucine and Lysine
Acetyl CoA or Acetoacetate –> Precursor for FA/Ketone Synthesis
Ketogenic/Glucogenic AAs
5
Isoleucine
Tryptophan
Phenylalanine
Tyrosine
Threonine
Glucogenic AAs
13
Valine
Histidine, Arginine, Asparagine, Glutamine
Methionine, Alanine, Aspartate, Glutamate, Glycine, Proline, Serine, Cysteine
Pyruvate/TCA Cycle Intermediates –> Gluconeogenesis Precursor
Consequences of Hyperhomocysteinemia and Homocystinuria
Deficiency in Met Metabolism
- Defective metabolism in homocysteine
- Vit B6, B12, folic acid deficiencies or inherited defects in enzymes (cystathionine B-synthase)
- Risk factor in atherosclerotic heart disease and stroke
Maple Syrup Urine Disease
Deficiency in BCA Metabolism (Val, Ile, Leu)
Deficient BCA a-ketoacid dehydrogenase complex (BCKD)
BCAs in urine
Higher in Mennonite, Amish, Jewish Populations
BCAs not degraded in Liver (no aminotransferase)
Phenylketonuria
Deficiency of Phe Metabolism
Phe is converted to _ by _
What is secondary PKU?
Defects in Phenyalanine Hydroxylase (PAH)
Converted to Tyrsonine via Phenylalinine Hydroxylase
Converted to phenylpyruvate and then to phenyllactate and phenylacetetate (Disrupts neurotransmission)
Tetrahydrobiopterin (BH4) deficiency (cofactor of PAH)
What are Transaminase Reactions?
What coenzyme do they require?
What is the clinical relevance of these enzymes?
Amino group transferred to a-ketoacid (coupled reactions)
Transaminases/Aminotransferases
Require PLP (Vit B6 derivative)
Clinical Relevance: ALT and AST biomarker for liver function
Tyrosine Derivatives
Tyr - Dopa –> Dopamine (Parkinsonism) –> Norepi –> Epi
Tyr –> Thyroid Hormones T3/T4 (Grave’s, Hyper/Hypothyroidism)
Tyr –> Melanin (Albinism)
Tryptophan Derivatives
Trp –> 5 -Hydroxytryptophan –> Serotonin –> Melatonin
Trp –> Niacin (Needs Vit B6) –> NAD+/NADP+
What is Thyroglobulin and how does it impact Thyroid Hormones?
How is hyperthyroidism treated?
Thyroglobulin made by thyroid and produces T4 and T3
Hyperthyroidism treated with agents which block iodination of thryroglobulin to decrease T4 and T3
Albinism and Tyrosinase
Albinism is due to severe lack of melanin (tyrosine –> melanin blocked due to tyrosinase defect)
Partial/Complete absence of pigmentation in skin, hair, and eyes
How does Parkinsonism develop?
Loss of conversion of Dopa to NT Dopamine in brain due to destruction of neural tissue.
L-Dopa treatment (dopamine can’t cross BBB)
How is ammonia removed in the brain and in muscle?
Brain: a-KG –> Glu –> Gln (glutamine synthase) w/ NH3 –> NH4+ to Urea Cycle
Muscle: Ala + a-KG –> Glu (ALT) –> NH4+ to Urea Cycle
Describe the Urea Cycle
NH4+ –> Carbamoyl Phosphate (Carbamoyl phosphate Synthetase (rate limiting step)
Carbamoyl Phosphate + Ornothine –> Citrulline
Citrulline converted up to Arginine (arginase removes ammonia and forms Urea)
Sent to Kidneys in the blood for excretion
Why is Ammonia Toxic?
What condition can it cause?
Toxic effects on brain and CNS since NH3 has ability to permeate membranes and causes pH imbalance
Mitochondrial dysfunction
How does diet affect the Urea Cycle?
Urea production increased in high protein diet, decreased in high CHO diet
Creatine is what 3 AAs?
Methionine, Arginine, and Glycine
