Test: Chemistry and Metabolism of Amino Acids- 3 - NEET PG MCQ

• Urinary metabolite associated with Vitamin B₆ deficiency: Xanthurenic acid.
• Urinary metabolites linked to Folic Acid deficiency: Formimino Glutamic acid and Homocystine.
• Urinary metabolites in Vitamin B₁₂ deficiency: Homocystine and Methyl Malonic Acid.

Metabolic by-products derived from Tyrosine include:

• Melanin
• Thyroxine
• Catecholamines (Dopamine, Epinephrine, Norepinephrine)

• Treatment for Classical PKU involves a diet low in phenylalanine.
• Another dietary therapy method includes the use of large neutral amino acids (LNAAs).
• Sapropterin dihydrochloride (Kuvan), a synthetic variant of BH₄, serves as a cofactor in patients with some residual PAH activity and is approved by the FDA to help decrease phenylalanine levels in PKU.
• Initial trials with recombinant phenylalanine ammonia lyase have shown promise, displaying reduced blood levels of phenylalanine during treatment.

• Alkaptonuria
• Albinism
• Pentosuria
• Cystinuria

• Normal life until the third or fourth decade
• Darkening of urine upon standing, the only sign in children
• In adults, ochronosis occurs, with alkapton bodies found in intervertebral discs, cartilage of the nose, pinna, etc.

• Alkalinisation which enhances urine darkening
• Benedict's test being positive in urine due to homogentisic acid acting as a reducing agent
• Positive ferric chloride test
• Positive silver nitrate test

The transformation of tyrosine into epinephrine consists of four consecutive stages:

• Ring hydroxylation,
• Decarboxylation,
• Side chain hydroxylation,
• N-methylation.

Amino acidurias and enzyme deficiencies include the following conditions

The final products resulting from the metabolism of Phenylalanine and Tyrosine are

Aminoaciduria enzyme deficiencies include:

Clinical manifestations of PKU typically present as follows:

• The affected infant appears normal at birth.
• If left untreated, significant cognitive impairment develops gradually.
• Delayed cognitive development may not be apparent during the first few months.
• Vomiting, which can sometimes be severe enough to be misdiagnosed as pyloric stenosis, may be an early indication.
• Affected infants generally have a lighter complexion compared to their unaffected siblings.
• Some may exhibit a mild seborrheic or eczematoid rash, which usually resolves as the child matures.
• These children often have a distinctive odour associated with phenylacetic acid, described as musty or mousey.

Neurological symptoms can include:

• Seizures in approximately 25% of cases.
• Spasticity and hyperreflexia.
• Tremors, with over 50% showing electroencephalographic abnormalities.

Common physical findings in untreated children include:

• Microcephaly.
• Prominent maxillae with widely spaced teeth.
• Enamel hypoplasia.
• Growth retardation.

• Serotonin (5 Hydroxy Tryptamine)
• Melatonin
• Niacin

• Melanin
• Thyroxine
• Catecholamines (Dopamine, Epinephrine, Norepinephrine)

Tyrosinemia Type I (also known as Tyrosinosis, Hereditary Tyrosinemia, or Hepatorenal Tyrosinemia) exhibits the following clinical manifestations:

• Initially, infants appear normal at birth, but symptoms typically arise between 2 and 6 months of age.
• An acute hepatic crisis usually marks the onset of the disease, often triggered by an intercurrent illness leading to a catabolic state.
• Common symptoms include:
• Fever
• Irritability
• Vomiting
• Hemorrhage
• Hepatomegaly
• Jaundice
• Elevated serum transaminases
• Hypoglycaemia
• An odour similar to boiled cabbage may be noticeable due to elevated methionine metabolites.
• As the individual ages, cirrhosis and eventually hepatocellular carcinoma may develop, although carcinoma is rare before the age of two.
• About 40% of affected children experience episodes of acute peripheral neuropathy resembling acute porphyria.
• These crises, often triggered by minor infections, are characterised by:
• Severe pain, frequently in the legs
• Hypertonic posturing of the head and trunk
• Vomiting
• Paralytic ileus
• Occasionally, self-inflicted injuries to the tongue or buccal mucosa
• Renal involvement manifests as a Fanconi-like syndrome, including:
• Normal anion gap metabolic acidosis
• Hyperphosphaturia
• Hypophosphataemia
• Vitamin D-resistant rickets
• Ultrasound examinations may reveal nephromegaly and nephrocalcinosis.
• Some infants may also present with hypertrophic cardiomyopathy and hyperinsulinism.

• Neurotransmitter in the brain
• Enhancement of mood
• Regulation of gastrointestinal motility
• Control of temperature
• Skin flushing resulting from vasoconstriction

Peculiar odours associated with various amino acidurias include:

Phenylketonuria arises from a lack of Phenylalanine Hydroxylase. A dietary limitation on Phenylalanine, coupled with the addition of Tyrosine, is essential since Tyrosine is a nonessential amino acid produced from Phenylalanine through the action of Phenylalanine Hydroxylase.

• Sulfur-containing amino acids include Cysteine and Methionine.
• The Guanidinium group is found in Arginine.
• Glycine is classified as a nonessential amino acid.

Biosynthesis of Glycine involves the following processes:

• Glycine Amino Transferase facilitates the formation of Glycine from Glyoxylate, Glutamate, and Alanine.
• It can also be produced from Serine through Serine Hydroxy Methyl Transferase, a reversible reaction.
• In invertebrates, Glycine is synthesised via the Glycine Synthase System.
• Additionally, it can be derived from Threonine using Threonine Aldolase.

Serine hydroxyl Methyltransferase

• By Glycine Synthase System in Invertebrates
• From Threonine by Threonine Aldolase

The Glycine Cleavage system comprises three enzymes along with an H Protein that is covalently bonded to a Dihydrolipoyl group. The three enzymes involved are:

• Glycine Dehydrogenase
• Amino methyl Transferase
• Dihydrolipomide Dehydrogenase

• Step I: Glycine Arginine Amidotransferase - This is the initial step in the kidney. The guanidino group from arginine is transferred to glycine, resulting in the creation of guanidinoacetic acid.
• Step II: Guanidinoacetate Methyltransferase - The second phase takes place in the liver. Here, creatine is produced, with S-adenosyl methionine acting as the methyl donor.
• Step III: Creatine Kinase - The third step occurs in the muscle, leading to the formation of creatine phosphate.
• Step IV: This final step happens spontaneously, resulting in the production of creatinine.

Glycine is transformed into Serine through the action of Serine Hydroxy methyl Transferase. The coenzymes needed for this process are Folic acid and Pyridoxal Phosphate.

Primary Hyperoxaluria Type I is the most prevalent variant of this condition. It arises from a deficiency in the peroxisomal enzyme alanine-glyoxylate aminotransferase, which is exclusively found in the liver peroxisomes and requires pyridoxine (vitamin B6) as a cofactor. This type involves a defect in protein targeting.

Primary Hyperoxaluria Type II (Glyceric Aciduria) is caused by a deficiency of D-glycerate dehydrogenase, part of the glyoxylate reductase enzyme complex.

Secondary Hyperoxaluria results from:

• Pyridoxine deficiency (the cofactor for alanine-glyoxylate aminotransferase)
• Ingestion of ethylene glycol
• High doses of vitamin C
• Administration of the anaesthetic agent methoxyflurane, which oxidises directly to oxalic acid
• Conditions such as inflammatory bowel disease or significant bowel resection (known as enteric hyperoxaluria)

Nonketotic Hyperglycemia is attributed to a defect in the Glycine Cleavage System.

• Glutathione is a tripeptide.
• It scavenges free radicals.
• Facilitates the transport of amino acids across the cell membrane.
• Maintains iron in the ferrous state, which helps to prevent the formation of methemoglobin.
• Functions as a coenzyme for specific enzymes.
• Involved in Phase II xenobiotic reactions during conjugation.

• PLP serves as the coenzyme for transsulfuration.
• The reaction is facilitated by the enzymes Cystathionine beta Synthase and Cystathionase.

The greater the presence of disulfide bonds, the more robust the keratin becomes. Cysteine plays a vital role in forming these disulfide bonds.