BCH 4024: Exam 2, Lecture 20 Amino Acids

All amino acids are derived from

Intermediates of glycolysis, the citric acid cycle, or the pentose phosphate pathway, using carbon skeletons from these metabolic routes as the base for amino acid synthesis.

Nitrogen source for amino acid synthesis

The amino groups of new amino acids are donated primarily by glutamate and glutamine, which act as central nitrogen carriers in metabolism.

Essential vs nonessential amino acids

Nonessential amino acids can be synthesized by the body from metabolic intermediates, while essential amino acids must be obtained from the diet because humans lack the enzymes to produce them.

Alanine formation reaction

Alanine is synthesized by transamination of pyruvate using the enzyme alanine aminotransferase (ALT), which transfers an amino group from glutamate to pyruvate.

Amino-group donor for alanine synthesis

Glutamate donates its amino group to pyruvate, forming alanine and α-ketoglutarate in a reversible reaction catalyzed by ALT.

Physiological role of alanine

Alanine serves as a key amino acid in the glucose-alanine cycle, transporting amino groups from muscle to the liver, where it helps in gluconeogenesis and ammonia detoxification.

Aspartate formation reaction

Aspartate is synthesized by transamination of oxaloacetate via aspartate aminotransferase (AST), using glutamate as the amino donor.

Asparagine synthesis enzyme

Asparagine synthetase catalyzes the amidation of aspartate, converting its carboxyl group to an amide group.

Amide donor and energy requirement in asparagine synthesis

Glutamine provides the amide nitrogen through an ammonia tunnel, and the reaction requires ATP to activate aspartate.

Asparagine breakdown

Asparaginase hydrolyzes asparagine to aspartate and free ammonia, an important reaction in nitrogen metabolism and some leukemia treatments.

Key takeaway for aspartate/asparagine metabolism

Know the specific enzymes (AST, asparagine synthetase, asparaginase), the role of glutamine as an amide donor, and that ammonia is channeled and not released freely during biosynthesis.

Glutamate formation

Glutamate is produced by transamination of α-ketoglutarate or by reductive amination of α-ketoglutarate via glutamate dehydrogenase, using either NADH or NADPH.

Alternative glutamate source

Glutaminase hydrolyzes glutamine to glutamate and free ammonia, a key step in tissues like the kidney and liver.

Importance of glutamate

Glutamate acts as the main amino-group donor for transamination reactions, a neurotransmitter, and a precursor for glutamine, GABA, and other biomolecules.

Arginine synthesis pathway

Arginine is synthesized as part of the urea cycle, where ornithine is converted to arginine through intermediates such as citrulline and argininosuccinate.

Creatine synthesis precursors

Creatine is formed from arginine, glycine, and methionine in the liver, pancreas, and kidney before being transported to muscle and brain.

Phosphocreatine function

Phosphocreatine (creatine phosphate) serves as a rapidly mobilizable energy reservoir, regenerating ATP from ADP via the enzyme creatine kinase, especially in muscles and neurons.

Creatinine formation and clinical relevance

Creatinine is a spontaneous, irreversible breakdown product of creatine and phosphocreatine; its blood concentration reflects kidney function, since it is excreted via glomerular filtration.

Tyrosine synthesis

Tyrosine is synthesized from phenylalanine by the enzyme phenylalanine hydroxylase, which adds a hydroxyl group to the aromatic ring.

Cofactor required for phenylalanine hydroxylase

Tetrahydrobiopterin (BH₄) acts as a reducing cofactor, regenerated from dihydrobiopterin (BH₂) after the reaction.

Tyrosine classification and importance

Tyrosine is conditionally essential, meaning it becomes essential if phenylalanine intake is insufficient. It serves as a precursor for catecholamines (dopamine, norepinephrine, epinephrine), thyroid hormones, and melanin.

Phenylalanine hydroxylase deficiency

A deficiency causes phenylketonuria (PKU), leading to toxic buildup of phenylalanine and neurological impairment if untreated.

SAM synthesis

Formed from methionine and ATP by methionine adenosyltransferase (MAT), linking the sulfur of methionine to the adenosyl group of ATP.

Biological role of SAM

SAM is the universal methyl-group donor in the body, transferring methyl groups to DNA, RNA, proteins, phospholipids, neurotransmitters, and hormones.

Reactions requiring SAM

Important methylation reactions include the synthesis of creatine and epinephrine from norepinephrine.

After methyl donation

SAM becomes S-adenosylhomocysteine (SAH), which is hydrolyzed to homocysteine; homocysteine can be remethylated to methionine using vitamin B₁₂ and tetrahydrofolate.

Methionine cycle significance

This cycle regenerates methionine but does not synthesize it de novo, making methionine an essential amino acid.

Amino acids composing glutathione

Glutathione is a tripeptide made of glutamate, cysteine, and glycine, linked by an unusual γ-peptide bond between glutamate and cysteine.

ATP requirement in synthesis

Two ATP molecules are required—one to form γ-glutamylcysteine and another to add glycine, catalyzed by glutamate-cysteine ligase and glutathione synthetase.

Main biological functions

Glutathione acts as a major cellular antioxidant, maintaining sulfhydryl groups in proteins in their reduced state, reducing peroxides via glutathione peroxidase, keeping heme iron in Fe²⁺ form, and donating electrons in DNA and lipid protection.

Pathway connection for regeneration

NADPH from the pentose phosphate pathway is used by glutathione reductase to regenerate reduced glutathione (GSH) from its oxidized form (GSSG).

Definition of nitrogen balance

A measure of nitrogen intake versus nitrogen loss, indicating whether the body is in a state of protein synthesis (positive balance) or degradation (negative balance).

Determinant of anabolic vs catabolic amino acid metabolism

The cell's energy status and amino acid demand determine whether amino acids are used for protein synthesis or broken down for energy and nitrogen excretion.

Glutamate

main excitatory neurotransmitter

Aspartate

excitatory neurotransmitter

D-serine

co-agonist of N-methyl D-aspartate (NMDA) receptor type glutamate receptors

Glycine

inhibitory neurotransmitter within spinal cord, brainstem, and retina

Tyrosine-derived neurotransmitters

dopamine, norepinephrine, epinephrine (catecholamines)

Glutamate-derived neurotransmitters

GABA

Histidine-derived neurotransmitters

histamine, cimeditine

Tryptophan-derived neurotransmitters

serotonin

Catecholamines

fight or flight, emotional/physical stress response, made in brain/nerve tissue/adrenal glands

Histamine

vasodilator in animal tissues, decarboxylated histidine

GABA

vitamin B6 dependent, inhibitor neurotransmitter, reduces neuronal excitability

Serotonin

derived from Trp, role in mood, sleep, digestion, blood clotting, sexual desire