Amino Acid Metabolism

Question 1

Protein Turnover and Dietary N

Answer 1

• Protein synthesis and degradation are constantly happening
  
  • Degradation removes old/damaged proteins
  • Degradation serves as a regeulation point
  • Degradation serves to release nutrients
  • 1-2% of body proteins are degraded per day
• Protein degradation (Ex: proteasome) releases free amino acids that can be used to build new proteins
  
  • Not completely efficient - not all amino acids can be recaptured/reused
  • New amino acids are constantly necessary to replace proteins
• Some amino acids can be synthesized by the body, but others must be obtained through the diet
  
  • Non-Essential: Ala, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser, Tyr
  • Essential: Thr, Val, Trp, Ile, Leu, Lys, Phe, Met
  • Species/Age Dependent: Arg, His

Question 2

Branched Chain Amino Acids

Answer 2

• BCAA (Leu, Ile, Val) are major components of muscle
• Up to 1/3 of skeletal muscle proteins are made up of BCAA
• BCAA are also used by the brain to synthesize neurotransmitters
• Most AA are metabolized by the liver, but the liver does not have enzymes for BCAA metabolism - metabolism happens in muscle

Question 3

Digestion

Answer 3

• Dietary proteins are hydrolyzed into component AA in the stomach and small intestine
  
  • The stomach is acidic and secretes pepsinogens, which are activated by the acid for the initial cleavage of proteins
  • The pancreas secretes several strong proteases (Ex: typsinogen, chymotrypsinogen) that are activated in the duodenum to continue protein cleavage
  • Products of cleavage are free AA and short (2-3 AA) peptides
• Neonates do not produce enough stomach acid in the first days of life and colostrum contains a trypsin inhibitor so they do not cleave proteins
  
  • Proteins can be absorbed whole for the first 1-2 days
  • Facilitates transfer of whole immunoglobulins for maternal immunity

Question 4

Absorption

Answer 4

• After cleavage, Amino acids and short peptides are absorbed in the late duodenum and jejunum by intestinal epithelial cells
• Intestinal epithelial cells hydrolyze most of the small peptides into free amino acids
• Absorbed and processed free amino acids are then transported into the blood were they enter portal circulation and go to the liver

Question 5

Using Amino Acids for Energy

Answer 5

• AA can be used as an energy source
• Most AA can be used for gluconeogenesis (glucogenic amino acids)
  
  • Alanine, Cysteine, Serine, Glycine, Aspartate, Asparagine, GLutamate, Glutamine, Proline, Histidine, Asparagine, Methionine, Valine
• Two AA (Leu, Lys) can only be used in the TCA cycle or form ketone bodies (ketogenic)
  
  • Leucine, Lysine
• 5 AA have portions of their carbon backbone used both for ketogenesis and gluconeogeness
  
  • Phenylalanine, Tyrosine, Threonine, Isoleucine, Tryptophan

Question 6

Transamination/Deamination

Answer 6

• The 1st step in AA catabolism is transamination followed by deamination
  
  • We saw this alanine in LC22
  • We will follow the NH4+ IN lc 25
• Multiple different transferases for different AA
  
  • Take an AA and convert to an a-keto acid
• Primarily occurs in liver (except BCAA - skeletal muscle)

Question 7

C2, C3, and Tryptophan: Pyruvate

Answer 7

• 3 Carbon AA can be converted into pyrubate
• 2 glycines (2 Carbons) can also be converted into pyruvate
• Tryptophan and threonine can be partially converted to pyruvate

Question 8

C4: Oxaloacetate

Answer 8

• 4 Carbon AA can be converted into oxaloacetate

Question 9

C5 and C6: a-ketogluterate

Answer 9

• Glutamate can be converted to a-ketogluterate
• Other 5+6 Carbon AA can be converted ino glutamate

Question 10

Branched Chain: Succinyl-coA

Answer 10

• Methionine and some BCAA can form propionyl-coA
• BCAA are transaminated in skeletal muscle (liver lacks enzymes)
  
  • Transamination produces alanine and glutamine- major exprots of skeletal muscle during starvation (>50% AA released from muscle are Alanine and Gln)
• Carbon backbones are eventually converted to succinyl-coA

Question 11

Aromatic: Fumarate

Answer 11

• Aromatic AA (Phe/Tyr) are preferentially metabolized by the liver in the fed state and BCAA are not (Ile/Leu/Val)
• Liver function can be measured by BCAA: Aromatic AA in circulation (BCAA:AAA)
• Liver failure can drastically raise AAA in circulation, cauing nerotransmitter dysregulatino in the braine
• Normal = 3:1
• Liver Disease as low as 1.5:1

Question 12

Gluconeogenesis

Answer 12

Question 13

Leucine and Lysine: Ketogenic

Answer 13

• Leucine and Lysine cannot form any glucogenic products, ONLY ketogenic
  
  • Forms acetoacetate and/or acetyl-CoA
  • Acetoacetate can be metabolized into acetyl-CoA
  • Although acetyl-CoA can enter the TCA cycle, it can’t donate any carbons to the TCA cycle components that can be used for gluconeogenesis because the two carbons are fully oxidized as CO₂
• Leucine is a BCAA - transamination is performed in muscle, no liver

Question 14

Isoleucine, Phenylalanine, Thronine, Tyrosine, (Tryptophan): Glucogenic and Ketogenic

Answer 14

• Portions of these amino acids were used in gluconeogenesis
• The remainder of these AA carbon backbones go to acetyl-CoA or acetoacetate
• When oxaloacetate is plentiful (not heavy gluconeogenesis), these can be used in the citrate cycle
• If oxaloacetate is low, these ae shunted into ketone bodies
• Tryptophan is very complicated - it can be metabolized down several different paths and produce differing amounts of glucogenic and ketogenic products

Question 15

Ketogenesis

Answer 15

• Ketone bodies are formed when oxaloacetate/free HS-CoA have been depleted
  
  • Oxaloacetate is used up by gluconeogeness
  • Free HS-CoA is used up by utilizing fat or ketogenic amino acids
• Ketogenesis:
  
  • Regenerates free HS-CoA
  • Supplies energy to tissues, especially heart and brain through ketone bodies
• (will discuss more later)