Comprehensive Notes on Carbohydrate, Lipid, and Protein Metabolism
- Three major pathways to know: glycolysis, Krebs cycle (citric acid cycle), and the electron transport chain (ETC).
- Glycolysis overview
- Occurs in the cytosol (cytosol of the cell).
- Glucose is broken down to pyruvate; yields two pyruvate molecules per glucose molecule.
- Net ATP produced from glycolysis: ext{Net ATP} = 2. (not a large amount, but it provides immediate energy)
- Pyruvate then moves from the cytosol into the mitochondria, specifically into the mitochondrial matrix.
- Pyruvate is converted to acetyl-CoA in the mitochondria.
- This acetyl-CoA then enters the Krebs cycle.
- Krebs cycle (citric acid cycle) overview
- Purpose is to generate high-energy electron carriers (NADH, FADH2) and other intermediates rather than large amounts of ATP directly.
- Start with oxaloacetate, cycle through, and end with oxaloacetate again.
- Major products: NADH and FADH2 (high-energy hydrogen carriers).
- These carriers feed into the ETC to extract more energy.
- Electron transport chain and chemiosmosis
- NADH and FADH2 donate electrons to the ETC; protons are pumped into the intermembrane space to generate a proton gradient.
- The gradient drives ATP production via ATP synthase.
- Molecular oxygen acts as the final electron acceptor, forming water when it accepts electrons.
- Large supply of high-energy hydrogen bonds (from NADH/FADH2) and the proton gradient drive the synthesis of ATP.
- Overall ATP yield from one glucose molecule
- Approximately ext{ATP per glucose} ext{ is in the range } 32 ext{--}38.
- Acetyl-CoA production and entry into Krebs cycle
- Pyruvate from glycolysis is transported into the mitochondrial matrix and converted to acetyl-CoA.
- Each glucose molecule yields two acetyl-CoA molecules to feed the Krebs cycle.
- Summary of energy flow (carbohydrates)
- Glucose → glycolysis in cytosol → pyruvate (2) → acetyl-CoA (2) → Krebs cycle → NADH/FADH2 → ETC → ATP
- Net ATP per glucose: 2 ext{ (glycolysis)} + ext{additional ATP from NADH/FADH2 in mitochondria}
ightarrow ext{total } 32 ext{--}38 per glucose.
- Lipid types and digestion
- Common lipids: triglycerides, steroids, etc.
- Lipids are broken down into fatty acids by lipase (salivary lipase and pancreatic lipase).
- Triglyceride structure: three fatty acids bound to a glycerol backbone (triacylglycerol).
- Lipid digestion begins in the mouth with lingual lipase; some digestion occurs in the stomach; most digestion occurs in the small intestine with bile emulsification aiding absorption.
- Absorption and transport
- Fatty acids are absorbed in the small intestine and re-form into chylomicrons, which are lipoproteins (lipids + proteins) that transport fats through the lymphatic system.
- Chylomicrons travel through the lymphatics and eventually enter the bloodstream via the subclavian vein.
- Lipids cannot travel freely in blood due to water incompatibility; lipoproteins solve this transport issue.
- Lipoproteins: LDL and HDL (and chylomicrons)
- Chylomicrons: transport dietary triglycerides; very high triglyceride content; low protein content.
- LDL (low-density lipoprotein): carries cholesterol to tissues; contains more lipid and cholesterol; ~20% protein; often called "bad cholesterol" when elevated because it deposits cholesterol in tissues and vessel walls.
- HDL (high-density lipoprotein): scavenges excess cholesterol and returns it to the liver; higher protein content (≈50% protein) and lower cholesterol content; called "good cholesterol" because it helps remove cholesterol from blood.
- LDL delivers cholesterol for steroid hormones (estrogen, testosterone, aldosterone) and cell membranes; cholesterol is embedded in cell membranes and used to synthesize hormones and membranes.
- Lipid energy and energy yield
- Lipids are a very efficient energy source: they yield about E{ ext{lipid}}
oughly 9.4 ext{ kcal/g}, while carbohydrates yield E{ ext{carb}}
oughly 4 ext{ kcal/g} and proteins yield E_{ ext{protein}}
oughly 4.3 ext{ kcal/g}. - Beta-oxidation: fatty acids are broken down two carbons at a time to form acetyl-CoA, which then enters the Krebs cycle and the ETC to produce large amounts of ATP.
- The energy payoff from lipids is high because a single fatty acid can generate many acetyl-CoA units, feeding multiple rounds of Krebs cycle and ETC.
- Ketone bodies and ketosis
- Excess acetyl-CoA from fatty acid oxidation can exceed the Krebs cycle capacity, leading to production of ketone bodies.
- Ketone bodies are acidic; accumulation can cause ketoacidosis if unmanaged (dangerous due to blood pH drop).
- Ketosis refers to the presence of ketones in the blood; not inherently dangerous, but ketoacidosis is dangerous when pH drops significantly.
- Ketogenic diet: significantly lowers carbohydrate intake, increases fat metabolism, and can lead to ketosis; brain can use ketones for energy; not equivalent to diabetic ketoacidosis.
- When to avoid lipids as a sole energy source
- Although lipids provide high energy, excessive dependence on beta-oxidation can lead to ketone accumulation and acidosis if Krebs cycle flux is limited.
- Protein digestion and synthesis overview
- Proteins are essential for structure, enzymes, clotting factors, collagen, etc.
- Protein digestion begins in the stomach with hydrochloric acid (denaturation) and pepsin (cleaves peptide bonds);
- Amino acids are absorbed in the small intestine.
- Amino acids are used to synthesize new proteins following transcription and translation: DNA → mRNA → ribosome reads mRNA → amino acids linked into a polypeptide chain → protein folds into a functional structure.
- DNA is not used for energy; RNA is involved in transcription/translation, and some RNA may be degraded to nucleotides (uric acid is a byproduct when nucleotides are degraded).
- How amino acids feed energy (when necessary)
- Amino acids can be deaminated (removal of amino group) to form a molecule that can enter energy pathways.
- Deamination yields ammonia (toxic) that must be converted to urea for excretion via the urea cycle; this protects against ammonia toxicity.
- After deamination, transamination can rearrange the amino acid to form intermediates that enter metabolic pathways (e.g., pyruvate, acetyl-CoA, oxaloacetate).
- Some amino acids can be converted directly into pyruvate, acetyl-CoA, or other Krebs intermediates, enabling entry into carbohydrate metabolism.
- Essential vs nonessential amino acids
- Essential amino acids: cannot be synthesized by the body and must be obtained from the diet.
- Nonessential amino acids: can be synthesized by the body (though some can be influenced by transamination to form others).
- Complete proteins contain all 10 essential amino acids (animal products are typical sources); incomplete proteins lack one or more essential amino acids.
- Food combinations (e.g., rice and beans) can yield a complete protein profile by providing all essential amino acids across meals.
- Nucleic acids and energy
- Nucleic acids (RNA/DNA) are not used for energy; RNA can be broken down to nucleotides, which can yield uric acid; uric acid buildup can contribute to gout in susceptible individuals.
Nucleic acids and energy considerations
- RNA is involved in protein synthesis (transcription and translation) but DNA is not used for energy production.
- RNA breakdown can yield nucleotide components, which can be metabolized; uric acid is a byproduct of nucleotide breakdown and can be linked to gout if elevated.
Metabolic states: absorptive, post-absorptive, and starvation
- Absorptive state (up to ~4 hours after a meal)
- Nutrients from the meal are absorbed and utilized.
- Digestion of carbohydrates begins in the mouth (salivary digestion) and continues in the small intestine; lingual lipase begins fat digestion in the mouth.
- Post-absorptive state (fasting)
- Occurs after the absorptive window when nutrients are no longer being absorbed.
- Blood glucose levels begin to fall; glucagon is released from the pancreas.
- The liver begins glycogenolysis (glycogen breakdown) to release glucose into the bloodstream and gluconeogenesis to maintain glucose levels.
- Starvation state (prolonged fasting)
- Body is deprived of adequate nutrition for an extended period.
- Primary objective: protect the brain; shift to fat metabolism and ketogenesis to provide energy in the form of ketones when glucose is scarce.
- Ketones can be used by the brain for energy; when fat stores are depleted, the body may break down muscle protein to generate glucose via gluconeogenesis.
- Ketone buildup can lead to acidosis if unchecked; the body may switch to gluconeogenesis as a final effort to maintain glucose and energy balance.
- Basal metabolic rate (BMR) vs metabolic rate
- BMR: energy expended to maintain basic physiological functions at rest under specific conditions.
- Metabolic rate: energy expenditure during normal activities; typically higher than BMR due to activity.
- Typical BMR estimates (no activity)
- Males: about 1{,}800 ext{ kcal/day}.
- Adult females: about 1{,}400 ext{ kcal/day}.
- Energy use distribution
- Approximately 70 ext{%} of basal energy is used to maintain organ function.
- Approximately 20 ext{%} for physical activity.
- Remaining energy supports maintaining body temperature.
- Factors that influence BMR
- Body composition: more muscle mass increases BMR (muscle burns more calories at rest).
- Sex: males typically have higher BMR due to greater muscle mass and organ size.
- Age: BMR generally decreases with age.
- Hormones: thyroid hormone has a major role in regulating metabolic rate; higher thyroid hormone increases BMR, lower thyroid hormone decreases it.
- Energy balance and weight management
- Weight gain occurs when energy intake exceeds energy expenditure over time.
- Weight loss occurs when energy expenditure exceeds intake.
- Calorie counting and exercise are common strategies to achieve energy balance.
- Thermal regulation and heat transfer
- Body temperature is regulated around a set point (roughly 36–38°C, i.e., 96–101°F).
- Important to keep temperature within a narrow range to avoid protein denaturation and other issues.
- Hypothalamus contains heat loss and heat-promoting centers to regulate temperature.
- When cold: vasoconstriction, shivering, increased thyroid hormone production to raise metabolic rate, conserve heat.
- When hot: vasodilation, sweating, cooling via evaporation; thyroid hormone production may be adjusted to reduce heat production.
- Modes of heat transfer
- Conduction: heat transfer by direct contact (e.g., skillet to food).
- Convection: heat transfer via air movement (e.g., convection ovens, air surrounding objects).
- Evaporation: cooling via sweat evaporation.
- Radiation: heat transfer via electromagnetic waves (e.g., infrared).
- Perspiration types
- Insensible perspiration: water loss through skin and lungs that is not consciously noticed.
- Sensible perspiration: visible sweating that can be measured.
Quick review and cross-links
- Carbohydrate metabolism anchors energy production: Glycolysis in cytosol, pyruvate to acetyl-CoA, Krebs cycle, ETC, ATP production.
- Lipids offer a high-energy source via beta-oxidation to acetyl-CoA, feeding Krebs and ETC; lipids require transport via lipoproteins (chylomicrons, LDL, HDL) to move through blood.
- Proteins provide energy only when needed; amino acids undergo deamination and transamination for entry into energy pathways; ammonia must be converted to urea for excretion.
- Three metabolic states guide energy usage: absorptive, post-absorptive, and starvation; ketosis/ketone bodies become a key energy source during prolonged fasting or carbohydrate restriction.
- Basal metabolic rate and thermoregulation determine the baseline energy needs and how the body maintains homeostasis under varying conditions.
Quick practice questions (based on lecture content)
- Which molecules are referred to as good cholesterol because they carry excess cholesterol from tissues to the liver for storage or secretion in the body? Answer: High-density lipoproteins (HDL).
- What process is responsible for the breakdown of fatty acids? Answer: Beta-oxidation.
- When carbohydrates are unavailable, cells will switch to which energy source? Answer: Lipids (fatty acids) via beta-oxidation.
- Synthesis of new organic molecules is what metabolic state? Answer: Anabolism.
- Which organelle is the site that provides the energy currency under catabolic conditions (where ATP is produced from nutrient oxidation)? Answer: Mitochondria.
- The energy yield per gram is highest for which macronutrient? Answer: Lipids (approximately 9.4 ext{ kcal/g}).
- True or false: DNA is commonly used to generate energy in metabolism. Answer: False; energy is produced primarily from carbohydrates, lipids, and proteins; RNA/DNA are not used for energy.
- What is the fate of excess acetyl-CoA if the Krebs cycle is saturated? Answer: Ketone bodies are produced (ketogenesis).
- What are the two types of heat transfer? Answer: Conduction and convection (plus evaporation and radiation as additional mechanisms).
- What is the purpose of the urea cycle in protein metabolism? Answer: To convert toxic ammonia (from amino group deamination) into urea for excretion.
