L4 Amino Acid Metabolism

Amino Acid Metabolism

• Amino acid metabolism involves essential amino acids and nitrogen balance.
• The TCA cycle categorizes amino acids as glycogenic or ketogenic, influencing their metabolic fates.
• This chapter also covers diseases: Cystinuria, Maple Syrup Urine Disease, PKU, Alkaptonuria, and Homocystinuria, each with distinct enzymatic defects.
• Not all amino acids can be synthesized by the human body; these must be obtained through diet.
• Daily requirements vary between adults and infants.

Amino Acid Biosynthesis

• The diagrams show the various pathways and intermediates in amino acid synthesis.
• Essential amino acids such as histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine cannot be produced by the human body.
• These diagrams illustrate the synthesis pathways, showing the steps and intermediates involved in the generation of these amino acids, utilizing various metabolic pathways.
• Specific pathways for branched-chain amino acids (BCAAs) are illustrated.

Nitrogen Balance

• Negative nitrogen balance occurs when nitrogen excretion exceeds intake, often seen in malnutrition or illness.
• Positive nitrogen balance occurs when nitrogen intake exceeds excretion, common in growth spurts or recovery from illness.
• An essential amino acid deficiency leads to negative nitrogen balance, hindering proper tissue repair and growth.
• Essential amino acid deficiency can lead to decreased protein synthesis.

Daily Requirements of Amino Acids

• The table presents the adult and infant daily requirements (in mg/kg) for various essential amino acids, aiding in dietary planning.
• Specific daily requirements for histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine are detailed in this table, important for growth and maintenance.

TCA Cycle Intermediates

• The TCA cycle intermediates are depicted in the diagram, showing the connections between amino acids, carbohydrates, and fatty acids.
• The diagram shows the cycle, its reactants, products, and enzymes.
• Amino acids like aspartate, glutamate, and others are associated with intermediates in the cycle, contributing to energy production.

Glycogenic and Ketogenic Amino Acids

• The diagram illustrates pathways for the classification of amino acids as glycogenic (glucogenic) and ketogenic, showcasing their catabolic fates.
• Some amino acids are both glycogenic and ketogenic, able to contribute to both glucose and ketone body production.

Ketogenic

• The diagram illustrates the pathways in the ketogenic metabolism (breakdown of amino acids into ketone bodies).
• Certain amino acids are strictly ketogenic (only yield ketone bodies), important for energy production during fasting or starvation.
• Ketogenic amino acids provide substrates for ketone body production.

Glycogenic Amino Acids

• The diagram shows the pathways in the glycogenic metabolism involved in the generation of glucose.
• Some amino acids primarily yield glucose or other intermediates utilized in gluconeogenesis, contributing to glucose homeostasis.
• Glycogenic amino acids yield glucose molecules.

Disorders of Amino Acid Metabolism

• The list displays various disorders related to amino acid metabolism and the enzymes affected.
• The table shows specific amino acids, enzymes involved, and the metabolic pathways affected in various disorders, highlighting the importance of specific enzymes for proper metabolism.
• Disorders such as Albinism, Alkaptonuria, Cystathioninuria, Histidinemia, Homocystinuria, Maple syrup urine, Phenylketonuria (PKU), and Argininemia are included.

Cystinuria

• The diagram illustrates cystinuria, a genetic disorder affecting the reabsorption of certain amino acids (cysteine, ornithine, lysine, and arginine) in the kidneys.
• This leads to the excretion of these amino acids in the urine.

Homocystinuria

• The diagram displays the pathway affected in homocystinuria, illustrating the involved enzymes (cystathionine synthase, cystathionine lyase, or homocysteine methyltransferase) and their functions in cysteine and methionine metabolism.
• Defects in these enzymes lead to the buildup of homocysteine and related metabolites.
• Homocystinuria is associated with specific clinical features like dislocated lenses.

Branched-Chain Amino Acids

• The diagram illustrates the metabolic pathways for branched-chain amino acids (BCAAs).
• Isoleucine, leucine, and valine undergo specific metabolic pathways, impacted in Maple Syrup Urine Disease, involving branched-chain α-ketoacid dehydrogenase.

Maple Syrup Urine Disease

• Symptoms include a characteristic urine odor (maple syrup), mental retardation, and muscle tone abnormalities, due to a defect in branched-chain α-ketoacid dehydrogenase.
• The disease is caused by a deficiency in specific enzymes involved in the metabolism of branched-chain amino acids.
• Maple Syrup Urine Disease results from defects in specific enzymes associated with BCAA metabolism.

Phenylalanine & Tyrosine Metabolism

• The diagram depicts the metabolic pathways for phenylalanine and tyrosine, emphasizing the enzymes involved, including phenylalanine hydroxylase.
• Metabolic disorders in this pathway include phenylketonuria (PKU), Tyrosinemia I, Tyrosinemia II, and Alkaptonuria.
• Disorders like Tyrosinemias (types I and II) and Alkaptonuria also occur, highlighting the essential roles of these enzymes.

Phenylketonuria (PKU)

• Symptoms include mental retardation, microcephaly, diet restrictions (low in phenylalanine), and a musty odor from phenylalanine metabolites, due to a lack of phenylalanine hydroxylase.
• Individuals with PKU often exhibit neurological and intellectual impairment.

Homogentisic Acid Oxidase

• The diagram shows the metabolic pathway for homogentisic acid, including related disorders.
• Alcaptonuria results from a deficiency in homogentisic acid oxidase, leading to accumulation of homogentisic acid and its excretion in urine.
• Individuals with this condition often experience dark urine and joint changes (ochronosis).

Triad of Alkaptonuria

• The characteristic triad of symptoms observed in alkaptonuria include dark urine, ochronosis (darkening of the joints), and arthritis, associated with homogentisic acid accumulation.

Propionic Acid Pathway

• The pathway for propionic acid is illustrated, with amino acids (valine, methionine, isoleucine, threonine), emphasizing the metabolic steps affected in various conditions.
• Defects in this pathway can lead to disorders, highlighted by specific symptoms. The pathway is involved in the metabolism of various amino acids.

Essential Amino Acids and Nitrogen Balance: Daily Requirements

• A table presents daily requirements for essential amino acids (mg./kg).
• This data aids in understanding dietary needs for optimal health and growth.
• Individuals need specific amounts of amino acids for optimal health, growth, and development.

This quiz covers essential concepts of amino acid metabolism, including nitrogen balance and the classification of amino acids in the TCA cycle. It also addresses important diseases related to amino acid metabolism and daily requirements for adults and infants. Test your knowledge on these crucial biological processes and their implications.