BIOC 3021 - Essay Exam 2

Asparagine basics

Neutral Polar, nonessential. (Asp, N)

ASNS gene

what gene codes for asparagine synthase?

asparagine synthase function

converts aspartic acid into asparagine alongside glutamine, which gets converted into glutamic acid

thought to help maintain the normal balance of the four amino acids in the body

importance of asparagine synthase reaction

links nitrogen metabolism with energy metabolism

asparagine is a precursor for:

aspartate, an amino acid that transmits signals between neurons

blood-brain barrier

asparagine is unable to cross this, so the brain relies on asparagine synthase

what does nonessential mean?

can be synthesized by the human body, not required to be in our diet

how is asparagine synthesized in humans?

through asparagine synthase, which converts aspartate and glutamine to asparagine and glutamate in an ATP-dependent amidotransferase reaction.

asparagine synthesis mechanism

1. Aspartate carboxyl is activated by an ATP-dependent process

2. Formation of β-aspartyl-AMP intermediate

3. Glutamine deamidation releases ammonia

4. Ammonia does nucleophilic attack on aspartyl, produces asparagine and glutamine

Features of R-group

amide, neutral polar (from carboxyamide), participates in hydrogen bond formation. In glycoproteins, the carbohydrates chain is often linked through this amide group.

asparagine role in body

Needed to produce many proteins as a precursor to other amino acids, break down toxic ammonia within cells, protein modification, and helps synthesize and release neurotransmitters

• Synthesis and N-glucosylation of proteins

• Nucleotide biosynthesis and ammonium metabolism

• An amino exchange factor

asparagine location in protein structure

usually found near beginning of alpha helices as “asx turns and asx motifs” due to its ability to form H-bonds, or as amide groups in beta sheets.

thought to “cap” hydrogen bond interactions that would be otherwise “capped” by the polypeptide backbone

asparagine regulates the uptake of?

serine, arginine, and histidine

asparagine as an intermediate

• breakdown produces malate, which can be oxidized in the citric acid cycle

• can also be hydrolyzed by asparaginase back into aspartic acid, a precursor to other amino acids, and ammonia

asparagine as a precursor

for those fasting (when cells are starved for nutrients), asparagine and aspartic acid are utilized as precursors for de novo synthesis of glutamine and alanine in muscle

asparagine deficiency effect on brain

affects the growth of neural stem cells during development, could also cause increased cell death in post-mitotic neurons or gilal cells either due to the accumulation of substrates or a deficiency in its products. (research still inconclusive)

deficency may also lead to an accumulation of aspartate/glutamate in the brain, resulting in more neuronal damage

asparagine deficiency

caused by a mutation in the ASNS gene, causes neurological problems after birth. pathology includes

• unusually small head size that worsens over time

• developmental delays in mental and motor skills

• exaggerated reflexes

• weak muscle tone

• epilepsy

• blindness

when is asparagine essential?

necessary and sufficient to suppress glutamine deficiency apoptosis without restoring levels of other nonessential amino acids or TCA cycle intermediates, eg. when the body is deficient in glutamine

purpose of asparagine in proteins

provides key sites for N-linked glycosylation, can modify protein chain with addition of carbohydrate chains. essential for proper protein folding, stability, and cell signaling

mechanism of asparagine deficiency

leads to reduced DNA, RNA, and protein synthesis, inhibition of cell growth, and activation of apoptotic cell-death mechanisms

what role does glutamine play in asparagine synthesis?

glutamine acts as a amide donor, transferring the amino group to aspartate and resulting in asparagine and glutamate.