Amino Acid Metabolism and Urea Cycle Overview

Amino acids are not stored in the body

• There is no “storage” protein in the body whose sole function is to maintain a supply of amino acids

  • Glucose is stored as glycogen

  • Fats are stored as triacylglycerols (TAG)

Amino acids have to be obtained from

• The ____

• Synthesized _____

• Produced from ______

diet, de novo, protein degradation

Catabolism of amino acids involves the removal of nitrogen which is released as: ____, ____, and _____

ammonia, urea, uric acid

Protein digestion

• In the stomach

  • HCl denatures the protein

  • HCl activates _____ to form _____,which breaks complex proteins to polypeptides

pepsinogen, pepsin

Protein digestion

• In the pancreas

• The protease enzymes _____, ______, _______,and _______ break downpolypeptides to oligopeptides

trypsin, chymotrypsin, elastase, carboxypeptidase

Protein digestion

• In the small intestine

• _______ cleave oligopeptidesto small peptides and free amino acidswhich are taken into the liver

Aminopeptidases

Catabolism of amino acids: Transamination

• Reaction(s) involving the removal of nitrogen from amino acids

• Removal of α-amino group

Reaction involves the transfer of the α-amino group to α-ketoglutarate to form ______ and an _____

glutamate, a-ketoacid

Catabolism of amino acids: Transamination

• Reaction(s) involving the removal of nitrogen from amino acids

• Removal of α-amino group

Reaction is catalyzed by an enzyme (______) along with a prosthetic group (_______)

aminotransferase, pyridoxal phosphate

Catabolism of amino acids: Transamination

• Two aminotransferases are

Alanine aminotransferase (ALT). Aspartate aminotransferase (AST)

Catabolism of amino acids: Transamination

• ______ (prosthetic group) transfers the amino group

Pyridoxal phosphate

Catabolism of amino acids: Transamination

• _________are all α-keto acids

• They have a –C=O group on the carbon adjacent to the –COOH group

Pyruvate, oxaloacetate, a-ketoglutarate

Catabolism of Amino Acids

• Oxidative deamination results in removal of the amino group as free ammonia

• Enzyme: _______

• Uses NAD+ or NADP+

glutamate dehydrogenase

Catabolism of Amino Acids

• Occurs in the liver and kidney

• Products are ________ and ______

• Ammonia is toxic, and is converted to urea in the liver

a-ketoacids, ammonia (NH3)

______ is the major disposal form of amino groups from amino acids

• Derived from ammonia, aspartate and carbon dioxide

• 90% of the nitrogenous components of urine

Urea

Synthesis and elimination of Urea

• Urea is produced in the _____, transported in the blood to the _____, and excreted in _______

liver, kidneys, urine

Synthesis and elimination of Urea

• Some urea is cleaved by ______ in the intestine into ammonia which is removed in the feces

• In kidney failure, high levels of urea are found in the blood

bacterial urease

Nitrogen elimination

• Removal of α-amino group of AA

  • _____ and ______

• NH3 is toxic

• Converted to urea in the liver

• Eliminated in the urine

Transamination, oxidative deamination

Amino acids that we have to get from our diet are ______ amino acids

essential

Amino acids that our cells can synthesize are______ amino acids

• have biosynthetic precursors in the carbohydrate and lipid biosynthetic pathways

nonessential

Type of amino acid: _____ amino acids

• Their catabolism yields pyruvate or intermediates of the TCA cycle

• These are substrates for gluconeogenesis

Glucogenic

Type of amino acid: _____ amino acids

• Their catabolism yields acetoacetate or its precursors, acetyl CoA and/or acetoacetyl CoA

• These are substrates for ketogenesis

• They do not give rise to the net formation of glucose

Ketogenic

List the ketogenic essential amino acids

Leucine (Leu,L), Lysine (Lys,K)

List the Glucogenic and Ketogenic essential amino acids

Isoleucine (Ile, I), Phenylalanine (Phe, F), Tryptophan (Trp, W)

List the Glucogenic essential amino acids

Histidine (His, H), Methionine (Met, M), Threonine (Thr, T), Valine (Val, V)

Amino acid biosynthesis can be divided into six families of pathways

Glutamate, aspartate, serine, alanine, aromatic AA, histidine

What is the source of Glutamate

a-ketoglurarate

What is the source of Aspartate

oxaloacetate (OAA)

What is the source of Serine

3-phosphoglycerate

What is the source of Alanine

pyruvate

What is the source of Aromatic Amino Acids

phsophoenolpyruvate, erythrose 4-phosphate

What is the source of Histidine

ribose 5-phosphate