Protein Biochemistry 2

Question 1

Nitrogen from amino acid ==> urea

Answer 1

1. transamination w/alpha-ketoglutarate
2. oxidative deamination

• One nitrogen of the urea molecule is supplied by free NH3 and enters the cycle and the other nitrogen is contributed by aspartate.
• Most amino acids are ultimately funneled to glutamate by means of transamination with α-ketoglutarate.

Question 2

Entry points for nitrogen into urea cycle

Answer 2

• NH3 freed from glutamate by glutamate dehydrogenase results in a free NH3 + α ketoglutarate. That NH3 then enter the Urea cycle by combining with CO2 to make Carbamoyl phosphate.
• The conversion of oxaloacetate to aspartate via transamination supplies the second NH3 for the cycle and enters after citrulline

Question 3

Rate limiting step of nitrogen entry into urea cycle + regulation

Answer 3

• Glutamate (Glutamate dehydrogenase) → α ketoglutarate + NH3
• It is allosterically activated by ADP and GDP.
• ATP and GTP are allosteric inhibitors of Glu dehydrogenase
• energy levels are low in the cell, amino acid degradation (by glutamate dehydrogenase) is high, facilitating energy production from the aa carbon skeletons.

Question 4

Characteristics of control points of urea cycle

Answer 4

• Carbamoyl phosphate synthetase 1 (CPS1)
  
  • This is the committed step of the urea cycle.
• N-acetyl glutamate allosterically activates CPS1.
  
  • Arginine is an activator of N-acetylglutamate synthase which forms N-acetyl glutamate.
  • N-acetyl glutamate causes unknown structural change in CPS1 that pushes the reaction forward.

Question 5

Characteristics of ammonia transport in blood

Answer 5

• Glutamine carries 2 ammonia molecules through the blood.
  
  • Most tissues use glutamine synthetase to convert glutamate to glutamine for transport to the liver for entrance into the urea cycle.
• Glucose-alanine cycle in muscles: allows for ammonia transport in blood as alanine, but it is minor.

Question 6

Characteristics of glucogenic amino acids

Answer 6

• Glucogenic: amino acids that can be used as substrates for gluconeogenesis → pyruvate or TCA intermediates
• Example: Aspartate (aspartate transamination) → oxaloacetate → gluconeogeneis

Question 7

Characteristics of ketogenic amino acids

Answer 7

• Ketogenic: amino acids that produce no net production of glucose but instead are fed into TCA cycle for energy.
• Lysine and leucine are the ketogenic amino acids since breakdown gives Acetyl-CoA which is only 2 carbons.

Question 8

Types of diseases related to nitrogen cycle/removal

Answer 8

• urea cycle disorders (UCDs)
• hyperammonemia
• Maple Syrup Urine Disease (MSUD)

Question 9

Characteristics of hyperammonemia

Answer 9

• Disorder of elevated ammonia in the blood due to urea cycle enzyme defects
• Leads to encephalopathy, coma, death

Question 10

Characteristics of Maple Syrup Urine Disease

Answer 10

• high concentration of branched amino acids
• Branched amino acids including valine, isoleucine, and leucine are broken down first by deaminases to their α keto acid forms, then they are decarboxylated.
• When there is decarboxylate deficiency, there is a buildup of α keto acids in the urine, which is sweet smelling.
• Several genetic deficiencies have been observed, and this can be fatal if not treated.

Question 11

Normal breakdown of branched amino acids

Answer 11

• Valine → α keto acid → Succinyl COA; (glucogenic)
• Isoleucine → α keto acid → Acetyl COA / Succinyl COA (ketogenic + glucogenic)
• Leucine → α keto acid → Acetyl CoA → (ketogenic)

Question 12

Production of thyroxin

Answer 12

• Thyroglobulin in the thyroid gland has ~140 tyrosines of which only 2-5 are iodinated
• By cleaving off one of the iodinated tyrosines we can then develop T3/T4.
• T4 (Thyroxin) is produced from tyrosine
  
  • Thyroid stimulating hormone (TSH) stimulated iodide uptake and release of T3/T4
  • Thyroid peroxidase oxidizes I- to I2

Question 13

Thyroxin modification and release

Answer 13

• T4 (deiodinase) → T3, which is a more active form of Thyroxin and has 1 less iodine
• T4 and T3 are transported from thyroid through blood via thyroxin binding globulin (TBG)

Question 14

Characteristics of heme metabolism

Answer 14

• Heme metabolism: Pyrole → Bilirubin → Porphyrin (Heme)
• Heme is produced in liver → part of production is in cytosol, part in mitochondria
• Four pyrole rings are put together in a cyclic formation
• Final step in producing heme is the iron addition step with the enzyme ferrochelatase

Question 15

Porphyrin definition

Answer 15

Porphyrins are cyclic molecules that bind metals

Question 16

Regulation of porphyrin production

Answer 16

• Porphyrin production is regulated by end product inhibition, as well as unnatural causes such as lead poisoining.
• Lead poisoining ==> lead displaces iron or zinc in two important reactions in heme production

Question 17

Poryphyrias definition

Answer 17

inherited defects in heme synthesis