Amino Acid and Nucleotide Metabolism

Flashcards covering topics discussed in the lecture notes.

Amino Acids

Precursors of many specialized biomolecules including vitamins, hormones, and pigments. Also used for host defenses, cellular redox balance, and energy metabolism.

Neurotransmitters

Amino acids are precursors. Glutamate makes GABA (g-aminobutyrate). GABA is an inhibitory neurotransmitter; underproduction is associated with epileptic seizures.

Histamine

Synthesized from histidine and is a powerful vasodilator in animal tissues. Cetirizine blocks histamine H1 receptors.

Phenylketonuria (PKU)

A condition resulting from diminished phenylalanine hydroxylase activity. Deficiencies in (BH4)-regeneration can also give rise to PKU.

PKU Symptoms

Accumulation of phenylalanine results in elevated side-reactions, which affects brain development and can cause seizures. High phenylalanine levels prevent transport of other amino acids across the blood-brain barrier.

Atypical PKU (BH4 deficiency)

To treat PKU resulting from tetrahydrobiopterin (BH4) deficiency, the precursors (DOPA and 5- hydroxytryptophan) are also supplemented in the diet.

PKU Treatment

Affected individuals must avoid consuming phenylalanine and monitor protein intake. Enzyme infusions can also be effective (Phenylalanine ammonia lyase converts Phe to cinnamic acid).

Nucleosides

Adenine makes Adenosine, Guanine makes Guanosine, Cytosine makes Cytidine, Thymine makes Deoxy-thymidine, Uracil makes Uridine

Nucleotides

Adenine makes AMP, Guanine makes GMP, Cytosine makes CMP, Thymine makes dTMP, Uracil makes UMP

Nucleotide Uses

Precursors for DNA and RNA, carriers of energy (ATP, GTP), cofactors (FAD, NAD, SAM, CoA), and second messengers (cGMP).

Purine Salvage Pathway

Recycle free bases and nucleosides. Adenine + PRPP makes AMP + PPi. Guanine and Hypoxanthine are salvaged by hypoxanthine-guanine phosphoribosyltransferase.

Lesch Nyhan Syndrome

Rare defects in hypoxanthine-guanine phosphoribosyltransferase gene (HPRT1 – X- linked) results in mental retardation, hostility, impaired kidney function, acute gouty arthritis.

Pyrimidine Salvage

Uracil -> Uridine -> UMP, Cytidine -> Uridine, Thymine -> Deoxy-thymidine -> dTMP, Cytidine -> CMP.

Dihydropyrimidine Dehydrogenase (DPD or DPYD)

Reduces uracil and thymine in pyrimidine degradation. Mutations can lead to Dihydropyrimidine Dehydrogenase Deficiency.

Purine Degradation (AMP)

AMP loses phosphate, then deaminated to inosine, ribose is cleaved to hypoxanthine, oxidized to xanthine, then oxidized to uric acid.

Purine Degradation (GMP)

GMP loses phosphate, ribose is cleaved to yield free guanine, deaminated to yield xanthine, then oxidized to uric acid.

Gout

An evolutionary loss of urate oxidase leads to uric acid accumulation. Joints become painful due to deposition of sodium urate crystals. Often results from under-excretion of uric acid.

Gout Treatment

Allopurinol inhibits xanthine oxidase, diminishing uric acid production. Dietary and lifestyle choices: reducing intake of meat/seafood, consuming adequate vitamin C, limiting alcohol/fructose and avoiding obesity. Also treat with non-steroidal anti-inflammatory drugs and painkillers.