Lecture 6: Protein and Amino Acid Metabolism

Question 1

Amino Acid Pool and where they come from/go

Answer 1

AA Pool - population of free amino acids (100g)

Come From:

1. body protein - 400g/day
2. dietary protein - 100g/day
3. synthed nonessential AA - varies

Go To:

1. body protein - 400g/day
2. porphyrins, creatine, neurotrans, nucelotides - 30g
3. glucose/glycogen, CO2, urea, FA, ketone - varies

Question 2

Hartnup Disease

Answer 2

• defective transport of nonpolar/neutral AA (Tryptophan) leads to conc. lvls in urine
  transporter: kidney/small intestine
• mainifests infancy: failure to thrive, nystagmus, tremor, ataxia, photosensitivity

Question 3

Cystinuria

Answer 3

• defective transport of dimeric cysteine/dibasic AA (Arg, Lys, Ornithine)
• form cysteine crystals in kidneys
• patients present w/renal colic (abdominal pain that comes in waves; linked to kidney stones)

Question 4

Pyruvate synthesizes what AA?

Answer 4

Alanine

Question 5

G3P synthesizes what AA?

Answer 5

Serine, Glycine, Cysteine

Question 6

Oxaloacetate synthesizes what AA?

Answer 6

Aspartate, Asparagine

Question 7

a-ketoglutarate synthesizes what AA?

Answer 7

glutamate, glutamine, proline, arginine

Question 8

Proteolytic Enzymes

Answer 8

• degradation of proteins for reabsorption

Exopeptidase: attacks at ends (C-terminus/N-terminus)
Endopeptidase: attacks within protein at specific site (internal peptide bonds)

Question 9

Intracellular Lysosomal vs Proteosomal Proteolytic Control

Answer 9

Lysosomal: lysosomes have >50 proteolytic enzymes that are active at pH 5, but inactive at pH 7 (cytoplasmic); NONSELECTIVE

• protects functional proteins from degradation in case of lysosomal rupture

Proteolytic: degrades polyubiquinated proteins; SELECTIVE

Question 10

Extracellular Proteolytic Control

Answer 10

• enzymes secreted as needed
• secreted as inactive zymogens (activated by proteolytic cleavage)
• enterokinase on intestinal epithelial cell (enteropeptidase) activate trypsinogen to trypsin
• trypsin activates more trypsinogen, and converts chymotrypsinogen to chymotrypsin

Question 11

Ketogenic Amino Acids (2)

Answer 11

Leucine and Lysine

• precursors for keto acids, ketone bodies, and fatty acids

Question 12

Ketogenic AND Glucogenic Amino Acids (5)

Answer 12

Isoleucine, Tryptophan, Phenylalanine, Tyrosine, Threonine

• can make either ketone bodies OR precursors for glucose synthesis/gluconeogenesis (TCA intermediates0

Question 13

What amino acids make Succinyl CoA?

Answer 13

Isoleucine, Valine, Methionine, Threonine

Question 14

What amino acids make a-ketoglutarate?

Answer 14

glutamate

glutamine, histidine, proline ,arginine

Question 15

What amino acids make fumarate?

Answer 15

phenylalanine, tyrosine

Question 16

What amino acids make oxaloacetate?

Answer 16

aspartate and asparagine

Question 17

What is a transaminase reaction and what are the enzymes called?

Answer 17

• the shuffling of amine groups (amino group transferred to an a-ketoacid)
• coupled rxns that utilizes transaminases (aminotransferases)
• required coenzyme: PRP (pyridoxyl-5-phosphate)
  
  • B6 derivative
  • alanine transaminase (ALT)
  • aspartate transaminase (AST)

Question 18

Hyperhomocysteinemia and homocystinuria

Answer 18

• B6, B12, folic acid deficiencies and genetic defects in enzymes cause defective homocysteine metabolism
• Hyperhomocysteinemia: risk factor in atherosclerotic heart disease, stroke, neuropsychatric illness
• lens dislocation, osteoprorsis, mental retardation

supplement w/vitamins

Question 19

Maple Syrup Urine Disease

Answer 19

• deficiency in branched-chain-a-keto acid dehydrogenase complex (BCKD)
• branched chain ketoaciduria (give urine maple syrup smell)
• blood accumulation causes toxic effect on brain = mental retardation
  treatment: thiamine supplementation, synthetic diet limiting BCAA

Question 20

Phenylketonuria (PKU)

Answer 20

• defects in activity of phenylalanine hydroxylase
• most common IEM (newborn screening)
• Phe converted to phenylpyruvate, then phenyllactate (must urine odor) and phenylactate
• later two disrupt neurotransmission and block AA transport in brain, as well as myelin formation

Secondary PKU –> defects in synthesis/regeneration of BH4

Question 21

What is a cardiac isoform that is used as a diagnostic serum marker for myocardial infarction?

Answer 21

creatine kinase (CK-MB)

Question 22

Albinism and Tyrosinase

Answer 22

• albinism due to severe lack of melanin
  (tyrosine –> melanin blocked by defective tyrosinase)
• also blocked by transfer of tyrosine in the body
• symptoms: missing pigment in skin, hair, eyes

Question 23

Thyroglobulin and thyroid hormones (hyperthyroidism)

Answer 23

• thyroglobulin used to produce T4/T3

- patients w/hyperthyroidism given agents that block iodination of thyroglobulin (dec. T3/T4 production)

Question 24

Removing Nitrogen from the body (Urea Cycle)

Answer 24

Ammonia: removed as Glu/Gln in brain
- removed as Gln/Ala in other tissue

Glutamine (2 amines), glutamate (1 amine) = excreted in urea cycle

Question 25

Ammonia Toxicity

Answer 25

• excessive ammonia due to disorders in urea cycle/liver failure has toxic effects on brain (NH3 toxic)
• cause pH imbalance, astrocyte swelling (cerebral edema, intracranial hypertension)
• glutamate –> a-ketoglutarate loses NH4, which inhibits TCA activity and inhibits postsynaptic excitatory proteins (depressed CNS activity)

Question 26

What three AA make creatine?

Answer 26

arginine, glycine, methionine

Question 27

Phosphocreatine

Answer 27

• storage form of energy in muscle, brain, and sperm
• quickly generate ATP

cardioselective isoform of creatine kinase in serum is used as a diagnostic for myocardial infarction