15.1 Overview of metabolic integration and regulation

Metabolic integration is all about keeping your body in balance. It's like a juggling act, where your cells constantly adjust how they use and store energy to meet your body's needs.

Enzymes are the key players in this balancing act. They speed up chemical reactions and can be turned on or off as needed, helping your body respond quickly to changes in energy demands or nutrient levels.

Metabolic Processes

Anabolism and Catabolism

• Metabolic homeostasis maintains a stable internal environment in the body by balancing anabolic and catabolic processes
• Anabolism builds complex molecules from simpler ones and requires energy input (ATP)
  • Examples of anabolic processes include protein synthesis, glycogen synthesis, and lipogenesis
• Catabolism breaks down complex molecules into simpler ones and releases energy (ATP)
  • Examples of catabolic processes include glycolysis, fatty acid oxidation, and amino acid catabolism
• Energy balance refers to the relationship between energy intake (from food) and energy expenditure (from physical activity and metabolic processes)
  • Positive energy balance occurs when energy intake exceeds expenditure, leading to weight gain
  • Negative energy balance occurs when energy expenditure exceeds intake, leading to weight loss

Metabolic Regulation and Homeostasis

• Metabolic homeostasis is maintained through the regulation of metabolic pathways by hormones, nutrients, and other signaling molecules
• Hormones such as insulin, glucagon, and cortisol play key roles in regulating glucose, lipid, and protein metabolism
  • Insulin promotes glucose uptake and storage, while glucagon stimulates glucose release from the liver
• Nutrients such as glucose, amino acids, and fatty acids can also regulate metabolic pathways through feedback mechanisms
  • High blood glucose levels stimulate insulin secretion, which in turn promotes glucose uptake and storage
• Disruptions in metabolic homeostasis can lead to metabolic disorders such as diabetes, obesity, and metabolic syndrome

Enzyme Regulation

Feedback Inhibition and Allosteric Regulation

• Feedback inhibition is a mechanism by which the end product of a metabolic pathway inhibits the activity of an enzyme earlier in the pathway
  • Example: ATP inhibits the activity of phosphofructokinase in glycolysis, preventing excessive ATP production
• Allosteric regulation involves the binding of a molecule (allosteric effector) to an enzyme at a site other than the active site, causing a conformational change that alters the enzyme's activity
  • Allosteric effectors can be activators or inhibitors, and they can be the substrate, product, or a different molecule altogether
  • Example: Fructose-2,6-bisphosphate allosterically activates phosphofructokinase in glycolysis, increasing its activity

Enzyme Regulation Mechanisms

• Enzyme activity can be regulated by various mechanisms, including:
  • Covalent modification: Addition or removal of chemical groups (e.g., phosphorylation, acetylation) that alter enzyme activity
  • Compartmentalization: Localization of enzymes in specific cellular compartments (e.g., mitochondria, peroxisomes) to control substrate access and pathway flux
  • Enzyme synthesis and degradation: Changes in the rate of enzyme synthesis or degradation can alter the total amount of enzyme available for catalysis
• These regulatory mechanisms allow cells to fine-tune metabolic pathways in response to changing energy demands and nutrient availability

Metabolic Integration

Metabolic Flux and Pathway Crosstalk

• Metabolic flux refers to the rate at which metabolites flow through a metabolic pathway
  • Flux is determined by the activities of enzymes in the pathway and the availability of substrates and cofactors
• Crosstalk between pathways occurs when metabolites or signaling molecules from one pathway influence the activity of enzymes in another pathway
  • Example: Acetyl-CoA, a product of fatty acid oxidation, can allosterically activate pyruvate carboxylase in gluconeogenesis, linking fat and carbohydrate metabolism
• Metabolic flux and pathway crosstalk allow cells to coordinate the activities of different metabolic pathways in response to changing energy demands and nutrient availability

Nutrient Sensing and Metabolic Adaptation

• Cells have evolved mechanisms to sense the availability of nutrients and adapt their metabolic activities accordingly
• Nutrient sensing pathways include:
  • AMP-activated protein kinase (AMPK): Senses cellular energy status (AMP:ATP ratio) and promotes catabolic pathways when energy is low
  • Mechanistic target of rapamycin (mTOR): Senses amino acid availability and promotes protein synthesis and cell growth when nutrients are abundant
• These nutrient sensing pathways can regulate metabolic enzymes and transcription factors to alter gene expression and pathway activity
  • Example: AMPK phosphorylates and inhibits acetyl-CoA carboxylase, reducing fatty acid synthesis when energy is low
• Metabolic adaptation allows cells to optimize their metabolic activities to match nutrient availability and energy demands, ensuring survival and growth under changing conditions