LMR - AMINO ACIDS and PROTEINS

Glutamine-Transport form of ammonia from brain and intestine to liver

Alanine - Transport form of ammonia from muscle to liver

Urea Cycle

Urea Cycle Disorders – Common Features

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Minimization of Brain Damage

❖ low-protein diet as frequent small meals

❖ Avoid sudden increases in blood ammonia levels
❖ Provide sufficient protein for growth and development
❖ Phenylbutyrate/ Buphenyl – used in management of urea cycle disorders
➢ Metabolized to phenylacetate (active molecule)
➢ Phenylacetate + Glutamine = Phenylacetylglutamine ---→rapidly excreted by the
kidneys
➢ Scavenges nitrogen
➢ Does not require metabolism via the urea cycle
➢ Methionine acts as methyl donor in the process of methylation. In methionine, the
thio-ether linkage (C–S–C) is very stable.
➢ In SAM, due to the presence of a high energy bond, the methyl group is labile, and may
be transferred easily to other acceptors

Transmethylation Reactions

Arginine forms
❖ Creatinine
❖ Nitric oxide
❖ urea
Glycine forms
❖ Creatinine

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❖ Heme
❖ Purine nucleotides
❖ Glutathione

Transamination reactions:

Cystinuria

❖ Deficiency in transport of amino acids

❖ Abnormal excretion of [COAL]
➢ Cystine
➢ Ornithine

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 ➢ Arginine
➢ Lysine
“Inborn errors of metabolism” coined by Garrod’s tetrad

❖ Alkaptonuria
❖ Albinism
❖ Pentosuria
❖ Cystinuria

Pheochromocytoma

❖ Catecholamine producing tumor

❖ Arising from chromaffin cells of the adrenal medulla
❖ Epinephrine excess
❖ ↑3-hydroxy-4-methoxy mandelic acid or vanillyl mandelic acid (VMA)

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Argentaffinomas /Carcinoid tumours

❖ Serotonin by argentaffin cells

❖ Small intestine/Appendix
❖ Serum level of serotonin is increased
❖ 60% (instead of 1 %) tryptophan is diverted to serotonin-→ niacin deficiency (pellagra)
❖ ↑urine HIAA (5-Hydroxyindoleacetic acid)

Tumor lysis syndrome

❖ Release their contents into the bloodstream--spontaneously or in response to therapy

❖ Characteristic findings of:
➢ Hyperkalemia
➢ Hyperuricemia
➢ Hyperphosphatemia
➢ Hypocalcemia

Chaperones

❖ Attach to nascent polypeptide chains and prevent wrong folding

❖ Help in the assembly of tertiary and quaternary structure of proteins.

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Calnexin and Calreticulin

❖ Act as chaperones for correct folding of glycoproteins

❖ Prevent aggregation of glycans
Spectrophotometric Estimation

❖ Proteins absorb ultraviolet light at 280 nm.

❖ Due to phenylalanine, tyrosine and tryptophan in the protein.
❖ Quantitative analysis
cGMP

❖ Photo Transduction in the eye

❖ ANF : Aterial Natriuretic Factor
❖ NO : Nitric Oxide
Secondary, Tertiary & Quaternary levels of protein structure are preserved by:

❖ Noncovalent bonds
➢ Hydrogen bonds,
➢ Electrostatic bonds
➢ Hydrophobic
➢ Van der Waals forces

Denaturation of Protein

❖ Primary structure is retained

❖ Loss of biological activity
❖ ↓ Solubility ↑ Precipitability
❖ Reversible denaturation-in CRD when the urea is removed by dialysis, the subunits are
reassociated and biological activity of immunoglobulin is regained.
❖ Irreversible denaturation – boiling of egg

Type – 1 Tyrosinemia/ Tyrosinosis/ Hepatorenal Tyrosinemia

❖ Deficiency- fumaryl acetoacetate hydrolase

❖ Symptoms by 6 months and death rapid
❖ Cabbage like odour and hypoglycemia

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❖ Urine-tyrosine, parahydroxyphenylpyruvic acid (p-HPPA) and hydroxyphenyllactic acid
❖ Serum-tyrosine
❖ TT-Tyrosine and phenylalanine restricted diet

Alkaptonuria

❖ Deficiency of homogentisate oxidase

❖ Excretion of homogentisic acid in urine.
❖ Compatible with fairly normal life
❖ Blackening of urine on standing
❖ Ochronosis
❖ Treatment-with pHPPA oxidase inhibitors

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Bile acid conjugating amino acids:

Amino Acids – Based on Metabolism

A. Purely ketogenic: Leucine & Lysine

B. Ketogenic and glucogenic: Isoleucine, Phenylalanine, Tyrosine & Tryptophan
C. Purely glucogenic: All the remaining 14 amino acids are purely glucogenic

Main function of Golgi apparatus:

❖ Protein sorting

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❖ Packaging
❖ Secretion

Amino acids having non-polar side chains:

❖ Hydrophobic and lipophilic (interior)

❖ Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Phenylalanine and Tryptophan.

Amino acids having uncharged or non-ionic polar side chains:

❖ Hydrophilic (exterior)
❖ Glycine, Serine, Threonine, Cysteine, Tyrosine, Glutamine and Asparagine
❖ (Tyrosine and Cysteine may show hydrophobic character when present in the interior of
the protein)

Amino acids having charged or ionic polar side chains:

❖ Hydrophilic (surface)
a. Acidic amino acids: Negative charge: Aspartic acid and Glutamic acid. (Tyrosine is mildly
acidic).
b. Basic amino acids: Positive charge: Lysine, Arginine and Histidine

Pellagra

❖ Deficiency of Tryptophan and Niacin

❖ More in women (tryptophan metabolism is inhibited by estrogen Metabolites)
❖ Dermatitis
• Casal’s necklace-Increased pigmentation around the neck
• Precipitated by exposure to sunlight
❖ Diarrhea
❖ Dementia
❖ 60 mg of tryptophan =1 mg of nicotinic acid
❖ Pellagra like symptoms in the maize eating population due to Tryptophan deficiency in
maize.

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Titration curve of glycine; pH in Y-axis

Isoelectric Point

❖ Molecule carries no net charge

❖ All the groups are ionized but the charges cancel each other
❖ No mobility in an electrical field
❖ Solubility and buffering capacity will be minimum
❖ pI = pK1+ pK2/2
❖ pI of glycine =2.4 + 9.8/2 = 6.1

❑ ❑ ❑

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