MCAT Biochemistry Chapter 12: Bioenergetics and Regulation of Metabolism

Biologcial Systems

• Biological studies are often performed on the cellular or subcellular level rather than the entire organism; these are considered closed systems

  • These systems have internal energy (U) and can have done on them in the form of heat

Physiological Conditions

• Biochemical analysis works well under standard conditions except pH; at 1 M concentration of protons, pH would equal 0 

• Modified standard state

  • [H+] ions 10^-7 M and the H is 7 ; ΔG is given the special symbol ΔG^°’, indicating that it is standardized to the neutral buffers used in biochemistry  

ATP

provides energy to the body in a readily available form

• The negative charge on its high energy phosphate bonds experience repulsive forces with one another 

Role of ATP

• is a mid-level energy carrier formed from substrate-level phosphorylation 

  • As a mid-level energy carrier, can easily pick up leftover energy and not waste the amount of energy a higher level carrier would

  • Provide about 30 Kj/mol under physiological conditions

Free Energy and Key Metabolic Phosphate Compounds

ATP Cleavage

• transfer of a higher-energy phosphate group from ATP to another molecule 

  • With phosphoryl group transfer, the overall free energy can be determined through summing free energies of individual reactions 

  • Phosphoryl Group Transfers can be used to form a phosphate group as reactant 

    • Ex: ATP donates phosphate group to glucose to form glucose-6-phosphate in glycolysis 

ATP hydrolysis

most encountered in coupled reactions using ATP as an energy source 

• the addition of water to break apart a phosphate molecule from ATP structure forming ADP or AMP

• ADP and P_i molecules that form after hydrolysis are stabilized by resonance, accounting for its very negative ΔG value 

Biological Oxidation and Reduction

• Oxidation reduction reactions are characteristic of oxidoreductase enzymes and are present in ATP synthesis/other biochemical pathways

  • See general chemistry chapters 11 and 12 (mostly 12)

Electron Carriers

• Several molecules in cytoplasm act as high energy electron carriers ; are soluble

  • Include NADH, NADPH, FADH₂ ubiquinone, cytochromes, and glutathione 

• There are also membrane bound electron carriers within inner mitochondrial membrane 

  • Ex: flavin mononucleotide (FMN)

  In general, proteins with prosthetic groups containing iron-sulfur clusters are particularly well suite for electron transport 

Flavoproreins (mostly FAD or FMN)

• Electron carriers containing a modified vitamin B₂ 

• Are nucleic acid derivatives 

• Most notable for presence in mitochondria and chloroplasts 

• Also function as coenzymes in oxidation of fatty acids, decarboxylation of pyruvate, reduction of glutathione

Homeostasis

•  physiological tendency toward a relatively stable state that is maintained and adjusted, often with expenditure of energy 

  • Reactions can proceed such that equilibrium is put off for a long time 

  • mediates metabolic stress

Postprandial (absorptive or well-fed) state

• Occurs shortly after eating (lasts 3-5 hours), and is marked by greater anabolism and fuel storage 

• Blood glucose levels rise and stimulate release of insulin (targets liver, muscle, adipose tissue)

  • Converts excess glucose to fatty acids (activates triacylglycerol synthesis) in adipose 

  • Encourages protein synthesis in muscles 

  • Promotes glucose entry in muscle/adipose tissue

Postaborptive (Fasting) State

utilizes counterregulatory hormoens

• have effect ons skeletal muscle, adipose, and the liver which are opposite to insulin;

  • glucagon : stimulates release of glucose in blood

• Gluconeogenesis processes gradually grow (max velocity at ~12hrs)

  • ↑epinephrine ↓insulin simulates release of amino acids from skeletal muscle and fatty acids from adipose tissue to provide carbon skeletons for gluconeogenesis 

Counterregulatory Hormones

• have effect ons skeletal muscle, adipose, and the liver which are opposite to insulin; include… 

  • Glucagon: stimulates release of glucose in blood

  • Cortisol

  • Epinephrine

  • Norepinephrine

  • Growth hormone 

Prolonged Fasting (starvartion)

• Levels of glucagon and epinephrine are markedly decreased 

• Gluconeogenic activity continues and plays an important role in maintaining blood glucose levels during prolonged fasting and depleted glucagon reserves

• Lipolysis is rapid resulting in excess Acetyl-CoA and production of ketone bodies

• Several weeks: 

  • Body and brain have shifted to ketone bodies as major energy source

  • Maintains amino acid quantities for essential protein functions

Hormone Regulation of Metabolism

• Water soluble peptide hormones are able to rapidly adjust metabolic processes of cells via second messenger cascadeds 

• Fat-soluble amino acid derivative hormones and steroid hormones enact-longer rance effects by exerting regulatory actions at transcriptional level

Insulin

• Peptide hormone secreted by B-cells of pancreatic islets 

• Tissues requiring insulin for effective uptake of glucse are adipose and resting skeletal muscle 

Tissue in which Glucose uptake is not affectd by insulin

• Nervous tissue 

• Kidney tubules 

• Intestinal mucosa 

• Red blood cells 

• Beta cells of pancrease 

Metabolic Effects of Insulin

• Increases

  • Glucose and triacylglycerol uptake by fat cells; 

  • glucagon synthesis

  • Lipoprotein lipase activity (clears VLDL and chylomicrons from blood)

  • Triacylglycerol synthesis in adipose tissue and the liver from acetyl-CoA

• Decreases 

  • Triacylglycerol breakdown (lipolysis)  in adipose tissue 

  • Formation of ketone bodies by the liver 

Glucagon

• Peptide hormone secreted by alpha cells of pancreatic islets

• Acts through secondary messengers 

Metabolic Effects of Glucagon

• Increases liver glycogenolysis 

  • activates glycogen phosphorylase/inactivates glycogen synthase 

• Increased liver gluconeogenesis 

• Increased liver ketogenesis and decreased lipogenesis 

• Increased lipolysis in the liver 

• Promoted by especially basic amino acids and low plasma glucose

Functional Relationship of Glucagon and Insulin

• Enzymes phosphorylated by glucagon are generally dephosphorylated by insulin 

• Enzymes phosphorylated by insulin are generally dephosphorylated by glucagon 

Glucocorticoids (metabolism)

• Secreted by adrenal cortex; are responsible for part of the stress response

  • During fight or flight; helps rapidly mobilize glucose from the liver to fuel actively contracting muscle cells while fatty acids are released from adipocytes

Cortisol

• glucocorticoid that promotes mobilization of energy stores through degradation and increased delivery of amino acids/lipolysis; elevates blood glucose levels 

  • Inhibits glucose uptake in tissue

  • Enhances activity of glucagon, epinephrine and other catecholamines

Catecholamines

• Are secreted by adrenal medulla; increase the activity of liver and muscle glycogen phosphorylase, promoting glycogenolysis 

• Increase lipolysis in adipose tissue 

• Include epinephrine and norepinephrine

Thyroid Hormones

• Increase the basal metabolic rate;

  • thyroxine (T₄) : increase occurs after 7 hour latency 

  • Triiodothyronine (T₃): produces a more rapid increase in metabolic rate

  • Accelerate cholesterol clearance form plasma and rate of glucose absorption

Liver and Metabolism

• Maintains a constant level of blood glucose under a wide range of conditons

• synthesize ketones when excess fatty acids are oxidized 

• Post meal, increase in insulin stimulates glycogen synthesis and fatty acid synthesis in the liver 

• Well fed state (after a meal):

  • Extracts excess glucose and use it to replenish glycogen stores

  • derives energy from oxidation of excess amino acids 

Adipose Tissue and Metabolism

• Elevated insulin stimulate glucose uptake and fatty acid release from VLDLs and chylomicrons 

• Glucose metabolised in adipocytes provide glycerol phosphate for triacylglycerol synthesis 

• hormone -sensitive lipase: activated by decreased insulin and increased epinephrine in fat cells, allowing fatty acids to be released

Skeletal Muscle and Metaboilism

Metabolism differs in skeletal muscle beased on resting and active states

Resting Muscle Metabolism

• After meal

  •  insulin promotes glucose uptake in skeletal muscle/replinishes glycogen stores

• In fasting state

  • Uses fatty acids derived from free fatty acids circulating in bloodstream, 

  • Ketone bodies used if fasting state is prolonged

Active Muscle Metabolism

• Primary fuel used to support muscle contraction depends on magnitude and duration of exercise 

• Moderately high-intensity continuous exercise

  • oxidation of glucose and fatty acids are imporatnt 

  • After 1-3 hours: glycogen stores become depleted, intensity drops to level that be supported by fatty acids 

Creatine Phosphate

important in ative muscle metabolism

• transfers a phosphate group to ADP to form ATP 

Cardiac Muscle Metabolism

• Prefer fatty acids as main fuel source 

• Use ketones when present during prolonged fasting 

Brain Metabolism

• Blood glucose levels tightly regulated to maintain sufficient continuous glucose supply 

  • Hypoglycemic conditions: hypothalamic centers sense drop in glucose and release glucagon/epinephrine 

• Uses ketone during periods of prolonged fasting 

Integrative Metabolism

• allows accurate measurements of respiratory quotient

  • Quotient differs depending on fuels being used by the organism 

    • Usually around 0.8 (indicating consumption of both fats and glucose)
      

Equation 12.3: Respiratory Quotient

RQ = CO₂ produced/ O₂ produced 

Calorimeters (BMR)

• measure basal metabolic rate (BMR) based on heat exchange with the environment 

  • Can be estimated based on age, weight, height, gender

Regulation of Body Mass

• Mass of carbohydrates and proteins 

  • Relatively stable but can be modified slightly by periods of prolonged starvation or significant muscle-building activities

• Lipids

  • Primary factor in gradual change of body mass over time 

  • Energy consumed > energy expended = fat stores accumulate 

  • Energy deficit = decrease in weight is observed

Basal Metabolic Rate (BMR) and Mass

• As individuals increase in basal metabolic rate, a caloric excess causes an increase in body mass until equilibrium is reached between new basal metabolic rate and existing intake 

• Deliberate alterations of body mass require alterations above the threshold (equilibrium) level 

  • This alteration is larger in negative energy balance than positive 

  • Larger changes must be made to lose than gain weight

Equation 12.4: BMI (body mass index)

BMI = mass / height²