Lect 8 Protein & AA Metabolism

Question 1

Amino Acid Pool is population of free AAs that is supplied by _ ? Depleted by _ ?

Answer 1

• Protein Turnover, Digested Food (essential AAs) , and De Novo Synthesis (nonessential AAs)
• Production of protein, Nitrogen containing compound synthesis, Degradation

Question 2

Proteolysis is _

Answer 2

Degradation of proteins for reabsorption

Question 3

Exopeptidase

Answer 3

attacks C- (carboxypeptidase) or N-terminus (aminopeptidase) ends

Question 4

Endopeptidase

Answer 4

attacks within protein at specific site (digests internal peptide bonds)

Question 5

What pH are proteases active in Lysosomal Degradation/Autophagy? Inactive?

Answer 5

Proteases active at acidic pH of lysosome (5), inactive at pH of cytoplasm (7)

Question 6

How does intracellular proteolytic control work?

Answer 6

Proteolytic enzymes controlled through “marking” mechanisms tagging protein substrate for degradation

Question 7

How does proteasomal degradation work?

Answer 7

Large proteasome cytoplasmic complexes cleave polyubiquinated proteins

Question 8

What is the Extracellular Proteolytic Control mechanism?

Answer 8

Proteolytic enzymes secreted as needed (inactive zymogens activated by proteolytic cleavage)

Question 9

Essential AA

PVT TIM HALL

Answer 9

• Phenylalanine (Phe)
• Valine (Val)
• Threonine (Thr)
• Tryptophan (Trp)
• Isoleucine (Ile)
• Methionine (Met)
• Histidine (His)
• Arginine (Arg)
• Leucine (Leu)
• Lysine (Lys)
• Glutamine (Gln)

Question 10

Nonessential AA

Answer 10

• Alanine (Ala)
• Aspartate (Asp)
• Asparagine (Asn)
• Cysteine (Cys)
• Glutamate (Glu)
• Gultamine (Gln)
• Glycine (Gly)
• Proline (Pro)
• Serine (Ser)
• Tyrosine (Tyr)

Question 11

Ketongenic AAs

2

Answer 11

Leucine and Lysine

Acetyl CoA or Acetoacetate –> Precursor for FA/Ketone Synthesis

Question 12

Ketogenic/Glucogenic AAs

5

Answer 12

Isoleucine

Tryptophan

Phenylalanine

Tyrosine

Threonine

Question 13

Glucogenic AAs

13

Answer 13

Valine

Histidine, Arginine, Asparagine, Glutamine

Methionine, Alanine, Aspartate, Glutamate, Glycine, Proline, Serine, Cysteine

Pyruvate/TCA Cycle Intermediates –> Gluconeogenesis Precursor

Question 14

Consequences of Hyperhomocysteinemia and Homocystinuria

Deficiency in Met Metabolism

Answer 14

• 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

Question 15

Maple Syrup Urine Disease

Deficiency in BCA Metabolism (Val, Ile, Leu)

Answer 15

Deficient BCA a-ketoacid dehydrogenase complex (BCKD)

BCAs in urine

Higher in Mennonite, Amish, Jewish Populations

BCAs not degraded in Liver (no aminotransferase)

Question 16

Phenylketonuria

Deficiency of Phe Metabolism

Phe is converted to _ by _

What is secondary PKU?

Answer 16

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)

Question 17

What are Transaminase Reactions?

What coenzyme do they require?

What is the clinical relevance of these enzymes?

Answer 17

Amino group transferred to a-ketoacid (coupled reactions)

Transaminases/Aminotransferases

Require PLP (Vit B6 derivative)

Clinical Relevance: ALT and AST biomarker for liver function

Question 18

Tyrosine Derivatives

Answer 18

Tyr - Dopa –> Dopamine (Parkinsonism) –> Norepi –> Epi

Tyr –> Thyroid Hormones T3/T4 (Grave’s, Hyper/Hypothyroidism)

Tyr –> Melanin (Albinism)

Question 19

Tryptophan Derivatives

Answer 19

Trp –> 5 -Hydroxytryptophan –> Serotonin –> Melatonin

Trp –> Niacin (Needs Vit B6) –> NAD+/NADP+

Question 20

What is Thyroglobulin and how does it impact Thyroid Hormones?

How is hyperthyroidism treated?

Answer 20

Thyroglobulin made by thyroid and produces T4 and T3

Hyperthyroidism treated with agents which block iodination of thryroglobulin to decrease T4 and T3

Question 21

Albinism and Tyrosinase

Answer 21

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

Question 22

How does Parkinsonism develop?

Answer 22

Loss of conversion of Dopa to NT Dopamine in brain due to destruction of neural tissue.

L-Dopa treatment (dopamine can’t cross BBB)

Question 23

How is ammonia removed in the brain and in muscle?

Answer 23

Brain: a-KG –> Glu –> Gln (glutamine synthase) w/ NH3 –> NH4+ to Urea Cycle

Muscle: Ala + a-KG –> Glu (ALT) –> NH4+ to Urea Cycle

Question 24

Describe the Urea Cycle

Answer 24

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

Question 25

Why is Ammonia Toxic?

What condition can it cause?

Answer 25

Toxic effects on brain and CNS since NH3 has ability to permeate membranes and causes pH imbalance

Mitochondrial dysfunction

Question 26

How does diet affect the Urea Cycle?

Answer 26

Urea production increased in high protein diet, decreased in high CHO diet

Question 27

Creatine is what 3 AAs?

Answer 27

Methionine, Arginine, and Glycine