Amino Acid Metabolism and Related Disorders: Biochemistry Review

How many amino acids can humans synthesize de novo?

Humans can synthesize 11 of the 20 amino acids, which are considered nonessential.

What are the essential amino acids that humans must obtain from their diet?

The 9 essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

What pathways provide the starting materials for amino acid synthesis?

Starting materials come from glycolysis intermediates, TCA-cycle intermediates, and existing amino acids.

What is the first step in amino acid degradation?

Deamination or transamination is usually the first step to remove the nitrogen-containing amino group.

What are the two major ways the amine group is removed during amino acid degradation?

Transamination and oxidative deamination.

What happens to waste nitrogen during amino acid degradation?

Waste nitrogen is converted to ammonia and then to urea for excretion.

What is the primary defect in classical phenylketonuria (PKU)?

Classical PKU is caused by a deficiency in phenylalanine hydroxylase (PAH).

What distinguishes malignant phenylketonuria (PKU) from classical PKU?

Malignant PKU is usually due to dihydropteridine reductase (DHPR) deficiency, affecting BH₄ regeneration.

What is the fate of phenylalanine in the presence of PAH?

Phenylalanine is converted to tyrosine with the help of PAH and tetrahydrobiopterin (BH₄).

What are the types of homocystinuria and their causes?

Type I is caused by cystathionine β-synthase deficiency or vitamin B₆ deficiency; Type II is due to a deficiency in methyl-B₁₂ synthesis; Type III is due to a deficiency in N⁵-methyl-THF synthesis.

What is the role of tetrahydrofolate (THF) in homocysteine metabolism?

THF participates in the remethylation of homocysteine.

What is the role of vitamin B₁₂ in homocysteine remethylation?

Vitamin B₁₂ works with folate to regenerate methionine from homocysteine.

What is S-adenosylmethionine (SAM) and its function?

SAM is an activated methyl donor formed from methionine and ATP.

What is the significance of the carbon skeleton after deamination?

The carbon skeleton can enter central metabolism for energy production or glucose/ketone synthesis.

What are the glucogenic and ketogenic metabolic intermediates?

Glucogenic intermediates can be converted to glucose, while ketogenic intermediates can be converted to ketone bodies.

What is the relationship between homocysteine and methionine in metabolism?

Homocysteine can be converted back to methionine through remethylation processes.

What is the primary problem in malignant PKU?

The primary problem is the inability to regenerate BH₄, affecting neurotransmitter synthesis.

What is the effect of elevated homocysteine in homocystinuria?

All forms of homocystinuria result in elevated levels of homocysteine and its metabolites.

What is the significance of dietary restrictions in classical PKU treatment?

Dietary restrictions target the main problem of elevated phenylalanine levels but do not correct all neurological consequences.

What are the key results of type I homocystinuria?

Type I results in elevated homocysteine due to a deficiency in cystathionine β-synthase or vitamin B₆.

How does DHPR deficiency affect catecholamine synthesis?

DHPR deficiency leads to decreased BH₄ regeneration, which in turn affects catecholamine synthesis.

What are glucogenic amino acids?

Amino acids whose carbon skeletons become pyruvate or TCA-cycle intermediates that can support gluconeogenesis.

What are ketogenic amino acids?

Amino acids whose carbon skeletons become acetoacetate or its precursors.

Which amino acids are exclusively ketogenic?

Leucine and lysine.

What is the primary pathway affected in primary oxaluria type I?

Glycine degradation, specifically the glycine → glyoxylate → oxalate pathway.

What enzyme is deficient in primary oxaluria type I?

Glyoxylate transaminase.

What is the clinical consequence of glyoxylate transaminase deficiency?

Increased oxalate levels leading to kidney stones and kidney damage.

What is alkaptonuria caused by?

Inherited deficiency of homogentisate oxidase, leading to accumulation of homogentisic acid.

What is a notable symptom of alkaptonuria?

Urine turns brownish-black when exposed to air.

Which amino acids are involved in the phenylalanine/tyrosine degradation pathway?

Phenylalanine and tyrosine.

What is maple syrup urine disease (MSUD) caused by?

Deficiency of the branched-chain α-keto acid dehydrogenase (BCKD) complex.

Which branched-chain amino acids are affected in MSUD?

Leucine, isoleucine, and valine.

What type of enzyme is the BCKD complex?

An α-keto acid dehydrogenase complex that performs oxidative decarboxylation.

What are the clinical clues for MSUD?

Newborn with vomiting/lethargy, sweet-smelling urine, ketones/keto acids, and elevated branched-chain amino acids.

What is the fate of waste nitrogen in amino acid metabolism?

It is converted to urea.

What is the role of phenylalanine hydroxylase (PAH)?

It converts phenylalanine to tyrosine.

What are the two processes for nitrogen removal in amino acid metabolism?

Transamination and oxidative deamination.

What is the relationship between homocysteine and methionine?

Homocysteine can be converted back to methionine with the help of THF and vitamin B₁₂.

What is the consequence of a defect in the CBS enzyme?

It leads to homocystinuria I, characterized by increased homocysteine levels.

What is the significance of SAM in one-carbon metabolism?

SAM is an activated methyl donor involved in the methylation of various substrates.

What is the main clinical feature of classical PKU?

Deficiency of phenylalanine hydroxylase (PAH).

What is the difference between classical PKU and malignant PKU?

Classical PKU is due to PAH deficiency, while malignant PKU is due to a defect in DHPR/BH₄.

What is the metabolic fate of branched-chain amino acids?

They undergo transamination to form branched-chain α-keto acids, which are then processed by the BCKD complex.

What is the primary clinical clue for diagnosing alkaptonuria?

Dark urine upon exposure to air.