METABOLISM OF INDIVIDUAL AMINO ACIDS

Introduction to METABOLISM OF INDIVIDUAL AMINO ACIDS

  • Protein metabolism denotes the various biochemical processes responsible for the synthesis of proteins and amino acids (anabolism), and the breakdown of proteins by catabolism.

Glycine

  • Simplest amino acid and is the only amino acid which does not exhibit optical isomerism
  • Non essential amino acid and glycogenic
  • Glycine in Proteins
    • Commonly occuring amino acid in protein structure.
    • The structural protein collagen has a high content of glycine.
  • Synthesis of Glycine
    • Serine
    • Threonine
  • Biologically important compounds synthesized from glycine
    • Synthesis of purine ring
    • Synthesis of heme
    • Formation of Glutathione
    • Glycine as conjugating agent
    • Glycine as neurotransmitter
    • Formation of creatine

CREATINE AND CREATINE PHOSPHATE

  • Serum
    • Creatine 0.2-0.6 mg/dl
    • Creatinine 0.6-1.5 mg/dl
  • Urine
    • Creatine 0-50 mg/day
    • Creatinine 1-2 g/day

Metabolic errors of Glycine

Glycinuria

  • Characterized by urinary excretion of 0.6g to 1g of glycine per day and a tendency to form oxalate renal stones
  • Results from defect in renal tubular re absorption.

Primary Hyperoxaluria

  • Arises from deamination of glycine, forming glyoxylate (oxalate semialdehyde).
  • Urinary excretion of oxalate is unrelated to dietary intake of oxalate.
  • Progressive bilateral calcium oxalate urolithiasis, nephrocalcinosis and re-current infection of the urinary tract are followed by early mortality from renal failure or hypertension.

ALANINE

  • Alanine can be synthesized by the transamination of pyruvate by glutamate-pyruvate aminotransferase (also called alanine transaminase, ALT). 
  • Non essential
  • glutamate + pyruvate <——-> a-KG + alanine
  • Also formed from 
    • Serine
    • Glycine
    • Cysteine
    • tryptophan

Glucose – Alanine Cycle

  • Glucose get converted to pyruvate in muscle tissue to generate energy.
  • Amino group from Glutamate is transferred to pyruvate to form alanine.
  • Alanine is exported to the liver via the blood stream where it is deaminated to pyruvate.
  • Must remove toxic ammonia it will convert to urea.
  • Pyruvate is get convert to glucose which is returned to the muscle for fuel.

BRANCHED CHAIN AMINO ACIDS

  • Valine is glucogenic; Leucine is ketogenic While Isoleucine is both ketogenic and  glucogenic.
  • All the three are essential amino acids.
  • Leucine is the major ketogenic amino acid
  • These amino acid serves as an alternate source of fuel for brain
  • Especially under the condition of starvation
  • All the three amino acids undergo similar sequence of reactions. 
  • Transamination, Decarboxylation and dehydrogenation.

Metabolic Disorders of Branched Chain Amino Acid Catabolism

Maple Syrup Urine Disease
(Urine with smell of burnt sugar)

  • It is also called branched chain ketonuria.
  • Incidence is 1 per 1 lakh Births.
  • The name originates from the characteristic smell of urine similar to burnt sugar or maple sugar due to excretion of branched chain keto acids.
  • An inherited disorder of the branched chain amino acids.
  • Occurs due to the absence of α-ketoacid decarboxylase or greatly reduced activity of the enzyme.
  • The conversion of all three branched chain α-keto acids to CO2 and acyl CoA-thioesters does not take place.

  Clinical features : 

  • The disease is manifested by the first week of extra uterine life.
  • Infant does not take feed and may vomit, child has poor muscle tone.
  • The patient may exhibit lethargy and convulsive seizures.
  • Excessive brain damage occurs in the surviving children and mental retardation
  • Biochemical findings
    • Plasma levels of the branched chain amino acids leucine, isoleucine , valine and their corresponding α– keto acids are  greatly enhanced.
    • Increased excretion of the branched chain amino acids and their corresponding keto acids in urine is noticed. The condition is called branched chain ketonuria.
    • The urine has a characteristic odour  which resembles that of maple syrup or burnt sugar.

Isovaleric Acidemia

  • The defect occurs due to impaired activity of isovaleryl CoA dehydrogenase involved in the leucine metabolism.
  • Isovaleryl – CoA accumulates, is hydrolysed to isovalerate and is excreted in the urine and sweat.
  • Symptoms include ‘cheesy odor’ of the breath and body fluids, vomiting, acidosis and coma precipitated by  excessive ingestion of protein. 

Propionic Acidemia

  • A disorder  that occurs due to the defect in the Propionyl – CoA carboxylase  deficiency that catalyses the conversion of  α Methylacetoacetyl – CoA to Acetyl – CoA  and Propionyl – CoA during catabolism of isoleucine.

Propionic  Acidemia

Other Biochemistry Notes

Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

VITAMIN D

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

. Blood Metabolism (Heme synthesis and breakdown)

Haemoglobinopathies

DNA Repair

Regulation of gene expression

DNA Replication

Transcription

Protein synthesis and genetic code

Detoxification (Xenobiotics)

Liver Function Test

Transamination Deamination & Urea Cycle

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