Test: Chemistry and Metabolism of Amino Acids- 2 - NEET PG MCQ

Glycine, which possesses the smallest R group, can fit into compact spaces and causes bends in the alpha helix. It is commonly found in beta turns.

• An amino acid capable of both protonation and deprotonation refers to those that can function as a buffer.
• An amino acid with a pKa equal to the pH of its environment possesses the greatest buffering capacity.
• The pKa of the imidazole group in histidine ranges from 6.5 to 7.4.
• At a pH of 7, the imidazole group of histidine can serve as a buffer.

• Glycine, Alanine, and Valine are solely glucogenic.
• However, Alanine serves as the primary glucogenic amino acid.

During extended fasting, there is a heightened rate of gluconeogenesis. Alanine, which is derived from muscle, serves as one of the substrates for gluconeogenesis. This process is referred to as the Glucose Alanine Cycle or the Cahill Cycle. Consequently, the plasma concentration of alanine increases during prolonged starvation.

• Transamination involves the conversion of a pair of amino acids and a keto acid.
• The keto acid produced from alanine through transamination is pyruvate.
• Oxaloacetate is the keto acid generated from aspartate during transamination.
• From glutamate, the resulting keto acid is α-ketoglutarate.
• This process is freely reversible.
• Transamination focuses on concentrating an amino group of nitrogen as L-glutamate.
• L-glutamate is the sole enzyme that experiences a significant degree of oxidative deamination in mammals.
• This reaction occurs via a ping-pong mechanism.
• It plays a crucial role in the biosynthesis of nutritionally non-essential amino acids.
• The mechanism is specific for one pair of substrates, while being nonspecific for others.
• Pyridoxal phosphate serves as the coenzyme.

The primary transport form of ammonia from various tissues, including the brain, is glutamine. In contrast, the transport form of ammonia from skeletal muscle is alanine.

The transport form of ammonia from the brain and the majority of other tissues is in the form of glutamine. This amino acid plays a crucial role in the metabolism of nitrogen and helps to maintain the balance of nitrogen within the body. In particular:

• Ammonia is primarily converted into glutamine to facilitate its transport.
• This conversion helps prevent toxicity from excess ammonia.
• Glutamine is then transported to the liver, where it can be further processed.

• Transporters for Neutral Amino Acids
• Transporters for Basic Amino Acids and Cysteine
• Transporters for Imino Acids and Glycine
• Transporters for Acidic Amino Acids
• Transporters for Beta Amino Acids (Beta Alanine)

• Oxoprolinuria: Caused by a deficiency in Oxoprolinase, leading to oxoprolinuria.

• Hartnup's Disease: Results in malabsorption of neutral amino acids, including the essential amino acid tryptophan. The defective protein identified is SLC6A19, the primary luminal sodium-dependent neutral amino acid transporter in the small intestine and renal tubules.
• Blue Diaper Syndrome (Drummond Syndrome): Involves indicanuria where tryptophan is specifically malabsorbed. The defect manifests only in the intestine and not in the kidney. Intestinal bacteria convert unabsorbed tryptophan to indican, causing the bluish tint in urine after hydrolysis and oxidation.
• Cystinuria: Dibasic amino acids such as cystine, ornithine, lysine, and arginine are absorbed via the Na-independent SLC3A1/SLC7A9 in the apical membrane, which is defective in cystinuria. This is the most common disorder associated with amino acid malabsorption.
• Lysinuric Protein Intolerance: Involves a defect in the SLC7A7 carrier at the basolateral membrane of intestinal and renal epithelium, preventing the delivery of cytosolic dibasic cationic amino acids into the paracellular space in exchange for Na⁺ and neutral amino acids.
• Oasthouse Urine Disease (Smith Strang Disease): A methionine-preferring transporter in the small intestine is thought to be affected, leading to a cabbage-like odour due to the presence of 2-hydroxybutyric acid, valine, and leucine.
• lminoglycinuria: Characterised by the malabsorption of proline, hydroxyproline, and glycine, resulting from a defect in the proton amino acid transporter SLC36A2.
• Dicarboxylic Aciduria: Linked to dysfunction in the excitatory amino acid carrier SLC1A1. This condition is associated with neurological symptoms, including POLIP (polyneuropathy, ophthalmoplegia, leukoencephalopathy, intestinal pseudo-obstruction).

Reactions of the Urea Cycle occur primarily in two locations: the first two reactions take place in the mitochondria, while the subsequent reactions occur in the cytoplasm.

• Carbamoyl Phosphate Synthetase-1 (CPS-I): Carbamoyl Phosphate is produced from the condensation of CO₂, ammonia, and ATP. CPS-I is considered the rate-limiting (pacemaker) enzyme in this pathway. It is only active when N-Acetyl Glutamate, an allosteric activator, is present. This step requires 2 moles of ATP.
• Transfer the carbamoyl group from Carbamoyl Phosphate to ornithine, resulting in the formation of citrulline. The following steps occur in the cytoplasm.

• Argininosuccinate Synthetase: This enzyme links the amino nitrogen from aspartate to citrulline, providing the second nitrogen for urea. This reaction necessitates ATP and utilises two inorganic phosphates.
• Argininosuccinate Lyase: This enzyme catalyses the cleavage of argininosuccinate into arginine and fumarate.
• Arginase: This enzyme hydrolytically cleaves arginine, releasing urea and reforming ornithine, which then re-enters the mitochondria.

Remember: All enzymes found in the cytoplasm begin with the letter 'A'.

• Carbamoyl-phosphate synthase I - Class 6 (Ligase).
• Ornithine carbamoyl transferase - Class 2 (Transferase).
• Argininosuccinate synthase - Class 6 (Ligase).
• Argininosuccinate lyase (Arginino-Succinase) - Class 4 (Lyase).
• Arginase - Class 3 (Hydrolase).

The location of urea production occurs in the mitochondria and cytosol of the liver. The amino acids that play a nearly exclusive role in the urea cycle are:

• Ornithine
• Citrulline
• Argininosuccinate

Four amino acids that do not experience any net loss or gain in the urea cycle include:

• Ornithine
• Citrulline
• Argininosuccinate
• Arginine

An increased level of ammonia in the blood indicates a potential urea cycle disorder. Therefore, the answer pertains to an enzyme within the urea cycle.

The processes occurring in two compartments include:

• Heme Synthesis
• Urea Cycle
• Gluconeogenesis

• Glutamate Dehydrogenase - oxidative deamination.
• Argininosuccinate Synthetase - urea cycle.
• Alpha Ketoglutarate Dehydrogenase and Isocitrate Dehydrogenase - TCA cycle.
• Fumarase - TCA cycle.

Glutamate Dehydrogenase (GOH). Liver Glutamate Dehydrogenase (GOH) is subject to allosteric inhibition by ATP, GTP, and NADH.

• Liver Glutamate Dehydrogenase (GOH) is allosterically activated by ADP.
• The reaction is reversible but predominantly favours the formation of Glutamate.
• It can utilise either NAD⁺ or NADP⁺.

In the given case clue to diagnosis are:

• High glutamine: Usually seen in hyperammonemia. Because Ammonia is the transport form of ammonia from brain and most other tissues. So in hyperammonemia Glutamine level is elevated.
• Increased uracil in urine can be seen in Ornithine Transcarbamoylase defect because as OTC defective, carbamoyl phosphate in mitochondria spills to cytoplasm. Then it enters into Pyrimidine synthesis. Pyrimidine intermediates and pyrimidines can accumulate. Hence, Uracil in urine.

The initial two phases of the urea cycle occur in the mitochondria, while the subsequent three stages take place in the cytoplasm. Ornithine reacts with Carbamoyl Phosphate to produce citrulline, facilitated by the enzyme OTC. Disorders can be linked to any of the steps involved in urea cycle disorders.

The nitrogen in urea is derived from ammonia and aspartate. ATP is necessary for both CPS-I and argininosuccinate synthetase. Among the five reactions involved, three take place in the cytoplasm. Therefore, the majority occur primarily in the cytoplasm. An increase in urea synthesis is observed with a high protein intake.

Statement b is incorrect because the rate-limiting enzyme of the urea cycle is carbamoyl phosphate synthase-I, not ornithine transcarbamoylase. Statement d is also incorrect because fumarate, not malate, is a byproduct of the urea cycle. The other statements are correct: urea is formed from ammonia, the cycle requires energy (ATP), and one nitrogen of urea comes from aspartate.

• Amino acid dehydrases for amino acids containing a hydroxyl group, such as serine and threonine.
• Histidase for histidine.
• Amino acid desulfhydrases for amino acids that have a sulfhydryl group, specifically cysteine and homocysteine.

Conservative mutation refers to the substitution of one amino acid with another that has similar properties. The characteristics of various amino acids are as follows: