MN15 - AA & Nucleotide Metabolism

What are the two components of amino acid catabolism?

The amino group (for nitrogen disposal via urea cycle) and the carbon skeleton (for carbohydrate or lipid metabolism).

What happens to the amino group during amino acid catabolism?

It is used for nitrogen disposal via the urea cycle.

What happens to the carbon skeleton of amino acids?

It enters carbohydrate metabolism (gluconeogenesis/TCA) or lipid metabolism (fatty acids/ketone bodies).

What are the 7 metabolic intermediates that amino acid carbon skeletons can form?

Pyruvate, oxaloacetate, fumarate, succinyl-CoA, α-ketoglutarate, acetyl-CoA, and acetoacetyl-CoA.

Which amino acids are purely ketogenic?

Leucine and lysine.

Which amino acids are both glucogenic and ketogenic?

Isoleucine, phenylalanine, tryptophan, and tyrosine.

What enzyme converts phenylalanine to tyrosine?

Phenylalanine hydroxylase.

Is phenylalanine to tyrosine conversion reversible?

No, it is irreversible.

What cofactor is required for phenylalanine hydroxylase?

Tetrahydrobiopterin (BH4).

What happens to BH4 during the reaction?

It is oxidized to BH2.

How is BH4 regenerated?

By dihydropteridine reductase.

What are major products derived from tyrosine?

Dopamine (catecholamines), thyroxine (thyroid hormone), melanin, fumarate, and acetoacetate.

What enzyme converts tyrosine to dopamine?

Tyrosine hydroxylase.

What enzyme converts tyrosine to melanin?

Tyrosinase.

What intermediate leads to fumarate and acetoacetate (from tyrosine)?

Homogentisate.

What enzyme metabolizes homogentisate (into fumarate + acetoacetate)?

Homogentisate oxidase.

Where are branched-chain amino acids primarily metabolized?

Muscle (not liver).

Are BCAAs essential amino acids?

Yes.

What is the first step of BCAA metabolism?

Transamination via B6-dependent aminotransferase.

What is the second step of BCAA metabolism?

Oxidative decarboxylation by BCKD complex.

What is the third step of BCAA metabolism?

FAD-linked dehydrogenations.

What type of amino acid is methionine?

Essential amino acid.

What important molecule is derived from methionine?

S-adenosylmethionine (SAM).

What is SAM's main function?

Major methyl group donor.

How is SAM formed?

Methionine condenses with ATP (all 3 phosphates removed).

What does SAM become after donating a methyl group?

S-adenosylhomocysteine (SAH).

What does SAH break down into?

Homocysteine and adenosine.

What happens to homocysteine when methionine is adequate?

Converted to cystathionine → cysteine (B6-dependent).

What happens to homocysteine during methionine deficiency?

Remethylated to methionine using N5-methyl-THF (B12-dependent).

What is the clinical significance of high homocysteine?

Causes oxidative damage and increases risk of vascular disease.

What vitamins are inversely related to homocysteine levels?

B6, B12, and folate.

What types of groups are transferred in one-carbon metabolism?

Methyl, methylene, and formyl groups.

What are the main carriers of one-carbon units?

THF derivatives and SAM.

What is the "active single-carbon pool"?

THF derivatives and SAM.

What vitamin is THF derived from?

Folic acid (vitamin B9).

What enzyme produces THF from folate?

Dihydrofolate reductase.

What cofactor is required for this reaction (folic acid → THF)?

NADPH.

What causes amino acid metabolism disorders?

Single-gene mutations causing enzyme deficiency.

What is the inheritance pattern of most AA metabolism disorders?

Autosomal recessive.

What is the general consequence of these disorders?

Accumulation of toxic metabolites leading to developmental abnormalities.

What enzyme is deficient in PKU?

Phenylalanine hydroxylase or BH4 reductase.

What accumulates in PKU?

Phenylalanine and phenylpyruvate.

What decreases in PKU?

Tyrosine and dopamine (if BH4 defect).

What are PKU symptoms?

Mousy urine odor, intellectual disability, developmental delay, hypopigmentation.

What is PKU treatment?

Low phenylalanine diet, tyrosine supplementation, or BH4 if needed.

What enzyme is defective in maple syrup urine disease?

Branched-chain α-ketoacid dehydrogenase (BCKD).

What accumulates in MSUD?

BCAAs and their ketoacids.

What are symptoms of MSUD?

Maple syrup urine odor, vomiting, ketoacidosis, intellectual disability.

What is treatment for MSUD?

Restrict BCAAs in diet.

What enzyme is deficient in homocystinuria?

Cystathionine synthase.

What accumulates in homocystinuria?

Homocysteine.

What decreases in homocystinuria?

Cysteine.

What are symptoms of homocystinuria?

Lens dislocation, long limbs, intellectual disability, thrombosis risk.

What is treatment for homocysteinuria?

Vitamin B12, folate, and methionine restriction.

What enzyme is deficient in albinism?

Tyrosinase.

What is the result of albinism?

Lack of melanin.

What are symptoms of albinism?

Hypopigmentation, vision problems, increased skin cancer risk.

What enzyme is deficient in alkaptonuria?

Homogentisate oxidase.

What accumulates in alkaptonuria?

Homogentisate.

What are symptoms of alkaptonuria?

Dark urine, ochronosis, early arthritis.

What is a nucleotide composed of?

A base (purine or pyrimidine), pentose sugar, and 1-3 phosphate groups.

What are purine bases?

Adenine and guanine.

What are pyrimidine bases?

Thymine, cytosine, and uracil.

What are the two pathways for nucleotide synthesis?

De novo and salvage pathways.

Where does de novo purine synthesis occur?

Mainly in the liver.

Where does purine salvage occur?

In all tissues.

What is the precursor of purine synthesis?

Inosine monophosphate (IMP).

What base does IMP contain?

Hypoxanthine.

What nucleotides are derived from IMP?

AMP and GMP.

What provides carbon atoms in purine synthesis?

N10-formyl THF and CO₂.

What provides nitrogen atoms in purine synthesis?

Aspartate and glutamine.

How are AMP and GMP regulated?

Feedback inhibition of their own synthesis.

What happens to AMP and GMP after synthesis?

Converted to ATP and GTP.

What enzyme converts ribonucleotides to deoxyribonucleotides?

Ribonucleotide reductase.

What is the purpose of purine salvage pathways?

To recycle bases using PRPP.

When is the pyrimidine ring synthesized?

Before attachment to ribose.

What enzyme catalyzes the first step of pyrimidine synthesis?

Carbamoyl phosphate synthetase II (CPS II).

What inhibits CPS II?

UTP and CTP.

What molecule is formed after cyclization of carbamoyl phosphate?

Orotic acid.

What does orotate combine with?

PRPP to form UMP.

What nucleotides are derived from UMP?

UTP and CTP.

How is dTMP formed?

dUMP is methylated by thymidylate synthase using N5,N10-methylene-THF.

What enzymes are involved in pyrimidine salvage?

Nucleoside phosphorylases.

What does uridine/cytidine phosphorylase do?

Adds ribose.

What does thymidine phosphorylase do?

Adds deoxyribose.

What does methotrexate inhibit?

Dihydrofolate reductase.

What does 5-fluorouracil inhibit?

Thymidylate synthase.

What does hydroxyurea inhibit?

Ribonucleotide reductase.