Biochemistry
Chemistry and Metabolism of Proteins
Protein metabolism for MBBS: protein structure, transamination, the urea cycle and inborn errors such as phenylketonuria and homocystinuria, mapped to NMC codes BI5.1 to BI5.5.
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Chemistry and Metabolism of Proteins
Protein metabolism for MBBS: protein structure, transamination, the urea cycle and inborn errors such as phenylketonuria and homocystinuria, mapped to NMC codes BI5.1 to BI5.5.
This chapter covers protein structure and the metabolism of amino acids. It explains the four levels of protein organisation, transamination and deamination, the urea cycle for ammonia disposal, and the inborn errors of amino acid metabolism that examiners test repeatedly.
High-yield: Chemistry and Metabolism of Proteins
- Proteins have four levels of structure: primary sequence, secondary alpha-helix and beta-sheet, tertiary folding and quaternary subunit assembly.
- The primary sequence of amino acids ultimately determines how a protein folds and functions.
- Nine amino acids are essential and cannot be synthesised in humans, so they must be supplied in the diet.
- Transamination transfers an amino group to a keto acid using pyridoxal phosphate, the active form of vitamin B6.
- Oxidative deamination of glutamate by glutamate dehydrogenase releases free ammonia for disposal.
- The urea cycle in the liver converts toxic ammonia to urea; carbamoyl phosphate synthetase-1 is its rate-limiting enzyme.
- Urea cycle enzyme defects and severe liver failure cause hyperammonaemia with encephalopathy.
- Phenylketonuria results from phenylalanine hydroxylase deficiency, giving raised phenylalanine, a musty odour and intellectual disability if untreated.
- Alkaptonuria is homogentisate oxidase deficiency, causing dark urine on standing and ochronosis.
- Maple syrup urine disease is a defect of branched-chain alpha-keto acid dehydrogenase affecting leucine, isoleucine and valine.
- Homocystinuria is most often cystathionine beta-synthase deficiency, causing lens dislocation, thrombosis and a marfanoid habitus.
- Glucogenic amino acids feed gluconeogenesis; the purely ketogenic amino acids are leucine and lysine.
- Nitrogen balance is positive during growth and pregnancy and negative in starvation, trauma and severe illness.
- The pI, or isoelectric point, is the pH at which an amino acid or protein carries no net charge and does not migrate in an electric field.
- Serum total protein and the albumin to globulin ratio help characterise liver disease, nephrotic syndrome and multiple myeloma.
Inborn errors of amino acid metabolism
- **Phenylketonuria:** Phenylalanine hydroxylase deficiency. Musty odour, intellectual disability if untreated.
- **Alkaptonuria:** Homogentisate oxidase deficiency. Dark urine on standing, ochronosis.
- **Maple syrup urine disease:** Branched-chain keto acid dehydrogenase defect. Sweet-smelling urine.
- **Homocystinuria:** Cystathionine beta-synthase deficiency. Lens dislocation, thrombosis.
NMC competencies in this chapter
- **BI5.1:** Structural organisation of proteins
- **BI5.2:** Metabolism of amino acids and the urea cycle
- **BI5.3:** Digestion and absorption of dietary proteins
- **BI5.4:** Common disorders associated with protein and amino acid metabolism
- **BI5.5:** Interpretation of laboratory results of protein analytes
Frequently Asked Questions
What are the four levels of protein structure?
Primary is the amino acid sequence, secondary is local folding into alpha-helices and beta-sheets, tertiary is the overall three-dimensional shape, and quaternary is the assembly of multiple subunits.
How does the body get rid of ammonia?
The liver converts toxic ammonia into water-soluble urea through the urea cycle, which is then excreted by the kidneys. A block in this cycle causes hyperammonaemia and encephalopathy.
What is the biochemical defect in phenylketonuria?
Deficiency of phenylalanine hydroxylase, which normally converts phenylalanine to tyrosine. Phenylalanine accumulates and causes intellectual disability unless a low-phenylalanine diet is started early.
Why does pyridoxal phosphate matter in amino acid metabolism?
It is the active form of vitamin B6 and the essential coenzyme for transamination reactions, which shuffle amino groups between amino acids and keto acids.
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