JNTU Pharm. D I Year MEDICIAL BIOCHEMISTRY Previous Question Paper (June/July - 2019 - R08)

Lipid metabolism is tightly regulated by hormones that control the balance between lipogenesis (fat storage) and lipolysis (fat mobilization). Insulin is the primary anabolic hormone; it promotes lipogenesis by stimulating acetyl-CoA carboxylase, the rate-limiting enzyme in fatty acid synthesis, and by increasing glucose uptake in adipose tissue to provide glycerol-3-phosphate for triglyceride synthesis. It also inhibits hormone-sensitive lipase (HSL), thereby preventing fat breakdown.

Conversely, catabolic hormones like glucagon, epinephrine, and cortisol stimulate lipolysis during fasting or stress. Glucagon and epinephrine bind to G-protein coupled receptors, activating adenylate cyclase to increase cyclic AMP (cAMP) levels. This activates protein kinase A, which phosphorylates and activates HSL, leading to the hydrolysis of stored triglycerides into free fatty acids and glycerol. Cortisol acts more slowly by promoting the expression of genes involved in lipolysis and inhibiting those involved in fatty acid storage, ensuring a steady supply of energy substrates during prolonged stress or starvation.

Co-enzymes are non-protein organic molecules, often derived from vitamins, that act as essential co-factors for enzyme activity by transferring chemical groups, electrons, or hydrogen atoms during metabolic reactions. Their importance lies in their ability to facilitate complex biochemical transformations that apoenzymes cannot perform alone, such as oxidation-reduction (e.g., NAD+, FAD), group transfer (e.g., Coenzyme A, pyridoxal phosphate), and isomerization.

In disease progression, co-enzyme deficiency or dysfunction disrupts metabolic pathways, leading to clinical pathologies. For example, a deficiency in thiamine pyrophosphate (TPP) impairs the pyruvate dehydrogenase complex, causing lactic acidosis and neurological damage as seen in Beriberi. Similarly, deficiencies in NAD+ or FAD disrupt the electron transport chain and TCA cycle, leading to cellular energy failure. Furthermore, the accumulation of metabolic intermediates due to impaired co-enzyme function can induce oxidative stress and cellular toxicity. Many chronic diseases, including diabetes and neurodegenerative disorders, are associated with impaired co-enzyme utilization, which exacerbates metabolic dysregulation and tissue damage.