Amino Acid Synthesis & Folate Cycle Learning Objectives

Which amino acid is the primary source of NH4+ for making amino acids?

Glutamate (main amino-group donor)

What are the steps in the process of glutamate being the primary source of amino groups?

1. Free NH4 is incorporated into a-ketoglutarate

2. Catalyzed by glutamate dehydrogenase

3. Produces glutamate

4. Glutamate donates its amino group to other carbon skeletons by transamination to make other AA

What molecules can provide carbon skeletons for amino acids?

Pyruvate, 3-phosphoglycearte, OAA, a-ketoglutarate

What are the metabolic pathways in which important carbon skeleton intermediates come from?

Glycolysis and Citric Acid Cycle

What are the amino acids synthesized from carbon skeletons that are from the glycolysis intermediate pyruvate?

Alanine, valine, leucine

What are the amino acids synthesized from carbon skeletons that are from the glycolysis intermediate 3-phosphateglycerate?

Serine, cysteine, glycine

What are the amino acids synthesized from carbon skeletons that are from the TCA cycle intermediate a-ketoglutarate?

Glutamate, glutamine, proline, arginine

What are the amino acids synthesized from carbon skeletons that are from the TCA cycle intermediate oxaloacetate ?

Aspartate, asparagine, methionine, threonine → Isoleucine, lysine

What is the proteinogenic amino acid that is synthesized in the Urea cycle?

Arginine

What is the vitamin whose derivative is a cofactor for amino acid transaminases?

The vitamin is B6 (pyridoxine), its derivative is PLP

What is the role of vitamin B6 derivative pyridoxal phosphate (PLP)?

PLP acts as a cofactor for transaminases and carries the amino group temporarily during transamination reaction. It does this by converting between PLP and PMP

→ amino-group shuttle in transamination

What is the cofactor used to transfer several different one-carbon units during cellular reactions?

Tetrahydrofolate (THF)

Name 5 different one-carbon units THF can transfer:

What is the vitamin in which THF cofactor is derived from?

THF is derived from folate (Vitamin B9)

What human population advised to ingest adequate levels of B9?

Pregnant women are advised to take B9 because adequate folate intake helps prevent neural tube defects in the fetus, such as spina bifida

What are donors of one-carbon units that operate in the folate cycle?

Serine, glycine, formaldehyde, formate, B12

What are acceptors of one-carbon units that operate in the folate cycle?

dUMP-dTMP, purine precursors, B12

What is the correct order of major one-carbon acceptors?

THF → B12 → SAM

What is the role of dihydrofolate reductase in DNA synthesis?

DHFR regenerates reduced folate cofactors needed for one-carbon transfer reactions that support DNA synthesis

What is the cause of phenylketonuria (PKU)?

PKU is caused by a defect in the gene encoding phenylalanine hydroxylase

What are the symptoms of PKU?

Acid buildup, fair/light skin, retardation

What is the treatment of PKU?

Reduced phenylalanine in the diet

Alanine

Aspartate

Glutamate

What is the alpha-precursor of alanine?

What is the alpha-precursor of Aspartate?

What is the alpha-precursor of Glutamate?