Amino Acid Metabolism- Study Guide

Humans ingest more protein (amino acids) than they need for replacement of endogenous proteins. These excess amino acids can not be stored and thus are catabolized (metabolized).

Ultimate Fate of "C": CO2, and energy (ATP) via TCA cycle and respiratory chain

Metabolic Fates of Amino Acids: You do not need to know this picture but you do need to know what Ketogenic and Glucogenic mean and which amino acids go into which pathways (see Below).

Ketogenic vs. Glucogenic:

Glucogenic- amino acids which can be converted into glucose (CHO producing), Pyruvate or a TCA cycle intermediate that can be converted to OAA is produced in the final step of its metabolism.

Ketogenic- amino acids which can be converted into fat (fat producing), Acetyl CoA or Acetoacetyl CoA is produced in the final step of their metabolism. (Acetyl CoA condenses with OAA so the net gain of OAA is zero since one molecule is consumed for each molecule produced (acetyl CoA))

Glucogenic Ketogenic Glucogenic & Ketogenic
Ala Gly Leu Ile
Arg His Lys Phe
Asn Met Trp
Asp Pro Tyr
Cys Ser
Gln Thr
Glu Val

Metabolism of Phe and Tyr (Liver): You do not need to draw this pathway but you do need to recognize its features and know the reactants, products and enzymes their co-factors and any consequences of their deficiencies. (See Below)

Demonstrates a number of important features common to Glucogenic and Ketogenic pathways:

(1) production of organic intermediates

(2) requirements for co-factors

(3) the possibility of inborn errors of metabolism at multiple steps

[1] Phenylalanine Hydroxylase: Phe -----> Tyr

Requires: oxygen

Co-factor: Tetrahydrobiopterin, synthesized by animals and other microorganisms.

Deficiencies: Phenylketonuria (PKU, common inborn error in metabolism), results in elevations of Phe, which if very high, prolonged --> permanent neurologic damage

Solution: dietary restriction of Phe, all newborns screened to detect PKU --> low Phe diet

Tetrahydrobiopterin Deficiencies: defects in synthesis can also result in elevations of blood Phe and severe neurologic disorders.

[2] Tyrosine Aminotransferase: Tyr -----> p-Hydroxyphenylpyruvate

Deficiencies: elevated blood Tyr (but not Phe since it is an irreversible reaction) ---> Tyr crystals form in tissues (cornea, palms, soles)

Solution: restrict dietary Tyr

[3] p-Hydroxyphenylpyruvate Oxidase: p-Hydroxyphenylpyruvate -----> Homogentisate

Co-factor: Ascorbic Acid

[4] Homogentisate Oxidase: Homogentisate ------> Maleylacetoacetate

Requires: Oxygen

[5] Maleylacetoacetate Isomerase: Maleylacetoacetate ----> Fumarylacetoacetate

Deficiency: severe "back-up" of the pathway producing very high levels of Phe and Tyr, usually occurs w/in the first months of life often requiring liver transplantation

Metabolism of Met and Cys: You do not need to draw this pathway but you do need to recognize its features and know the reactants, products and enzymes their co-factors and any consequences of their deficiencies. (See Below)

Features:

(1) pathway for excretion of sulfur generated from the sulfur containing amino acids: Met and Cys

(2) co-factors: cobalamin and folic acid

(3) important "methyl" group generator for synthesis of a number of cmpds.

[1] Methione Adenosyltransferase: Met ----> Homocysteine

Transfer of Methyl onto adenosine resulting in S-Adenosylmethione (SAM)

SAM- "methyl" donor during synthesis of creatine, phosphatidylcholine, epinephrine etc.

Homocysteine -----> Met: cobalamin (B12) containing enzyme, methylcobalamin donates a "methyl" group to homocysteine.

[2] Cystathione-b-synthase: Homocysteine ----> Cystathione

Co-factor: pyridoxine

Deficiency: homocystinuria, increased levels of homocysteine which has a reactive sulfur group that can bind to a number of proteins.

[3] Cystationase: Cystathione ----> Cysteine

Co-Factors- Review

Co-Factors: Organic and Inorganic

Organic: Prosthetic Groups (i.e. Heme) and Co-enzymes (derived from water soluble vitamins)

Water Soluble Vitamins

Pyridoxine (B6): Used in many rxns, particularly those involving transamination. Conversion of homocysteine to cystathione.

Cobalamin (B12): Used in conversion of homocysteine to methione.

Folic Acid: Used in the synthesis of folates important in "methyl" group transfers.

Vitamin C (Ascorbic Acid): Used in many reactions, primarily as a reducing agent.

© Dr. Noel Sturm 2013