4.2 Major Coenzyme Functions

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Thiamine pyrophosphate (TPP) acts as a coenzyme for multiple enzyme complexes:

• Pyruvate dehydrogenase complex (PDH) – Converts pyruvate into acetyl-CoA, a crucial step linking glycolysis to the Krebs cycle. Real-life relevance: When PDH is impaired, the brain—highly dependent on glucose—faces an energy shortfall, leading to confusion and neurological symptoms.

• α-Ketoglutarate dehydrogenase (KGDH) – Functions in the Krebs cycle, catalyzing the conversion of α-ketoglutarate to succinyl-CoA. Real-life relevance: Essential for maintaining ATP supply in neurons; reduced activity is implicated in Alzheimer’s and Parkinson’s disease.

• Branched-chain α-keto acid dehydrogenase (BCKDH) – Breaks down branched-chain amino acids (valine, leucine, isoleucine). Real-life relevance: Critical for muscle energy and recovery; deficiency affects athletes and patients with metabolic disorders.

• Transketolase – Key enzyme in the pentose phosphate pathway, facilitating ribose and NADPH production. Real-life relevance: Supports antioxidant defense and DNA synthesis; compromised activity increases oxidative stress in the brain.

• 2-Hydroxyacyl-CoA lyase 1 (HACL1) – Participates in peroxisomal α-oxidation of fatty acids. Real-life relevance: Important for lipid metabolism in neural tissue.

• 2-Oxoadipate dehydrogenase (OADH) – Involved in degradation of lysine and tryptophan. Real-life relevance: Affects neurotransmitter balance and mitochondrial health.