OIA1003 AMINO ACID METABOLISM

Gastric Protein Digestion

Begins in the stomach with pepsin + HCl → forms short peptides.

Pancreatic Enzymes

Trypsin, chymotrypsin, carboxypeptidase hydrolyze polypeptides in the small intestine.

Brush Border Enzymes

Aminopeptidase breaks oligopeptides into free amino acids.

Amino Acid Transport

Absorbed via active transport, enter bloodstream → body cells

Amino Acid Pool

Total circulating free amino acids from: Dietary proteins, Liver synthesis, Protein turnover

Why Remove α-Amino Group?

It prevents oxidative degradation; removal is needed for energy extraction.

Step 1: Transamination

Transfers amino group to α-ketoglutarate → forms glutamate.

Transamination Enzymes

Aminotransferases, cofactor = pyridoxal phosphate (PLP) (Vit B6 derivative).

Diagnostic Enzymes

↑ ALT & AST in blood → liver or heart damage.

Step 2: Oxidative Deamination

Glutamate is deaminated by glutamate dehydrogenase → releases NH₄⁺.

Function

Converts toxic ammonia to urea, excreted in urine.

Location

Starts in mitochondria, ends in cytoplasm of liver cells.

Inputs of Urea Cycle

NH₃, CO₂, Aspartate, ATP

Outputs of Urea Cycle

Urea, ADP, Fumarate

Urea Cycle Steps

Carbamoyl phosphate

Citrulline

Argininosuccinate

Arginine

Urea + Ornithine

Glucogenic Amino Acids

Converted to pyruvate or TCA intermediates → glucose synthesis.

Ketogenic Amino Acids

Converted to acetyl-CoA or acetoacetyl-CoA → ketone bodies.

Dual-Action Amino Acids

Some are both glucogenic & ketogenic (e.g., isoleucine, phenylalanine).

Exclusively Ketogenic

Leucine and lysine.

Fate of Carbon Skeletons

All amino acids enter TCA cycle intermediates or glycolytic pathway.

Glucogenic Role (Starvation)

Catabolized to pyruvate, α-ketoglutarate, oxaloacetate → gluconeogenesis.

Ketogenic Role

Converted to acetyl-CoA → fuels ketogenesis in the liver.

Phenylketonuria (PKU) cause

Deficiency of phenylalanine hydroxylase.

PKU Pathology

Phenylalanine → phenylpyruvate (neurotoxic)

↓ Melanin → hypopigmentation

PKU Symptoms

Mental retardation, seizures, fair skin & blue eyes

PKU Treatment

Low-phenylalanine diet, avoid aspartame, supplement tyrosine

Maple Syrup Urine Disease (MSUD)

Defect in branched-chain α-keto acid dehydrogenase

MSUD Accumulation

Leucine, isoleucine, valine and their keto-acids → CNS damage

MSUD Signs

Vomiting, acidosis, maple syrup odor in urine

MSUD Treatment

Vomiting, acidosis, maple syrup odor in urine

Albinism

Defect in tyrosine metabolism → ↓ melanin

Albinism Symptoms

Hypopigmented skin, hair, eyes, light sensitivity

Homocystinuria

Deficiency of cystathionine β-synthase

Homocystinuria Markers

↑ Homocysteine & methionine in blood/urine

Homocystinuria Symptoms

Dislocated lens, skeletal defects, early atherosclerosis

Homocystinuria Treatment

Restrict methionine, supplement B6, B12, folate

Alkaptonuria

Deficiency of homogentisic acid oxidase

Alkaptonuria Signs

Black urine, arthritis, dark pigment in cartilage

Alkaptonuria Treatment

Low-phenylalanine/tyrosine diet

Overall Catabolism Flow

Transamination (PLP-dependent)

Oxidative deamination (NH₄⁺ release)

Urea cycle for nitrogen disposal

Carbon skeletons enter gluconeogenesis or ketogenesis