Cell Metabolism and Energy Production

Metabolism

• Human body releases energy from chemical bonds in nutrients, which breaks down to release energy
• Energy, water, and carbon dioxide are released during metabolism

Cellular Structure

• Cells are the work centers of metabolism, with similar structures
• Cells have two basic parts: nucleus and cytoplasm
• Mitochondria in cells are the power generators that contain energy-generating pathways

Energy-Yielding Nutrients

• Glucose is derived from carbohydrates
• Glycerol and fatty acids are derived from lipids (triglycerides)
• Amino acids are derived from proteins

Catabolic Pathways

• Stage 1: Hydrolysis of complex molecules to their component building blocks
• Stage 2: Conversion of building blocks to acetyl CoA
• Stage 3: Oxidation of acetyl CoA; oxidative phosphorylation
• Catabolic pathways involve complex to simple molecules, exergonic reactions, oxidations, and require NAD+
• Convergent process

Anabolic Pathways

• Precursor molecules are converted to complex molecules
• Endergonic reactions require ATP
• Anabolic pathways involve simple to complex molecules, endergonic reactions, reductions, and require NADPH
• Divergent process

Comparison of Catabolic and Anabolic Pathways

• Key differences between catabolic and anabolic pathways:
  • Direction of molecules (complex to simple vs simple to complex)
  • Energy requirement (exergonic vs endergonic)
  • Redox reactions (oxidations vs reductions)
  • Co-factors required (NAD+ vs NADPH)
  • Process type (convergent vs divergent)

Energy Currency and ATP-ADP Cycle

• ATP (adenosine triphosphate) is the energy currency in biological systems.
• ATP is broken down into ADP (adenosine diphosphate) and Pi (inorganic phosphate) through hydrolysis, releasing free energy to drive endergonic reactions.
• ATP is formed from ADP and Pi when fuel molecules are oxidized, and this cycle is the fundamental mode of energy exchange in biological systems.

Redox Reactions

• Oxidation: the loss of hydrogen and oxygen from a molecule.
• Reduction: the gain of hydrogen and oxygen by a molecule.

Regulation of Metabolism

• Intracellular signals that regulate metabolism include substrate availability, product inhibition, and allosteric activators.
• Intercellular communication involves chemical signaling through hormones, which trigger second messengers such as cAMP, cGMP, and Ca/phosphatidylinositol.

Metabolic Fuels

• Carbohydrates, lipids, and proteins are used as metabolic fuels, with glucose being the major metabolic fuel of most tissues.
• Glucose, fatty acids, and amino acids are used as energy sources.

Oxidative Phosphorylation

• The process involves the pumping of hydrogen ions into the outer chamber of the mitochondrion, driven by the electron transport chain.
• The energy generated is used to form ATP through oxidative phosphorylation.

Energy Metabolism Control

• Continual release of energy from glucose when cells don't need energy is a wasteful process.

ATP's Role in Glycolysis Control

• ATP inhibits the enzyme phosphofructokinase, controlling energy metabolism.

ADP's Role in Glycolysis Control

• ADP (and AMP) increases phosphofructokinase activity, having the opposite effect of ATP.
• When ATP is used by the cell, newly formed ADP and AMP turn on energy processes again.

Citric Acid Cycle's Impact on Glycolysis

• Citrate ion, formed in the citric acid cycle, strongly inhibits phosphofructokinase, preventing the glycolytic process.

ATP-ADP Cycle

• ADP and AMP are almost instantly returned to the ATP state after energy processes are turned on.

Anaerobic Release of Energy

• Anaerobic glycolysis is a lifesaving measure for up to a few minutes when oxygen becomes unavailable.
• Formation of lactic acid during anaerobic glycolysis allows for the release of extra anaerobic energy.
• Reconversion of lactic acid to pyruvic acid occurs when oxygen becomes available again.

Lactic Acid

• Lactic acid is used by the heart for energy.
• Lactic acid can be converted back to pyruvic acid when oxygen is available.

Pentose Phosphate Pathway

• The pentose phosphate pathway provides energy independently of the citric acid cycle enzymes.
• This pathway is an alternative for energy metabolism when certain enzymatic abnormalities occur in cells.

Blood Glucose

• Normal blood glucose concentration is around 90 mg/dl after 3-4 hours of fasting.
• Blood glucose levels rarely rise above 140 mg/dl after a meal containing carbohydrates, unless in cases of diabetes mellitus.
• The regulation of blood glucose concentration is closely related to the pancreatic hormones insulin and glucagon.

Protein Structure

• Amino acids combine into long chains through peptide linkages
• Some protein molecules consist of multiple peptide chains linked by hydrogen bonding between CO and NH radicals

Blood Amino Acid Concentration

• Normal concentration of amino acids in the blood: 35-65 mg/dl
• Amino acids exist in the blood primarily in the ionized state due to their acidic nature

Post-Prandial Amino Acid Concentration

• Amino acid concentration in the blood increases after a meal, but only by a few milligrams per deciliter

Amino Acid Regulation

• Renal threshold for amino acids: regulates plasma amino acid concentration
• Storage of amino acids as proteins in cells
• Release of amino acids from cells to regulate plasma amino acid concentration

Hormonal Regulation

• Growth hormone and insulin: increase formation of tissue proteins
• Adrenocortical glucocorticoid hormones: increase plasma amino acid concentration

Types of Plasma Proteins

• The three major types of protein present in the plasma are albumin, globulin, and fibrinogen.

Functions of Albumin

• Albumin provides colloid osmotic pressure in the plasma, preventing plasma loss from capillaries.

Functions of Globulins

• Globulins perform several enzymatic functions in the plasma.
• Globulins are responsible for both natural and acquired immunity of the body against invading organisms.

Functions of Fibrinogen

• Fibrinogen polymerizes into long fibrin threads during blood coagulation, forming blood clots that help repair leaks in the circulatory system.

Plasma Protein Formation

• The liver can form plasma proteins at a rate of up to 30 g/day.

Plasma Proteins as a Source of Amino Acids

• Plasma proteins serve as a source of amino acids for the tissues.

Deamination and Transamination

• Deamination is the removal of amino groups from amino acids.
• Transamination is promoted by several enzymes, including aminotransferases, which are derivatives of pyridoxine (Vitamin B6).

Protein Metabolism

• Urea diffuses from liver cells into body fluids and is excreted by the kidneys.

Protein Degradation

• 20-30 grams of protein are degraded daily, even when no proteins are consumed, known as obligatory loss of proteins.
• This degradation process involves deamination and oxidation of amino acids.

Effect of Starvation on Protein Degradation

• Proteins in tissues degrade rapidly, up to 125 grams daily, during starvation.
• As a result, cellular functions deteriorate rapidly.

Hormonal Regulation of Protein Metabolism

• Growth hormone stimulates protein synthesis by increasing transcription, leading to the creation of new cellular proteins.
• Insulin facilitates protein synthesis by accelerating the transport of specific amino acids into cells, which serves as a stimulus for protein synthesis.

Effects of Glucocorticoids on Protein Metabolism

• Glucocorticoids increase the breakdown of most tissue proteins, except in the liver, by enhancing the rate of extrahepatic protein degradation.

Effects of Testosterone on Protein Metabolism

• Testosterone promotes protein deposition in tissues, particularly in muscles, where it increases the deposition of contractile proteins.

Effects of Thyroxine on Protein Metabolism

• Thyroxine indirectly affects protein metabolism by increasing the overall metabolic rate of cells, leading to a subsequent impact on protein synthesis and breakdown.

Lipid Metabolism

• Triglycerides and other lipids are transported from the gastrointestinal tract to adipose tissue, skeletal muscle, and heart through lymph via chylomicrons.
• Lipoprotein lipase is synthesized in adipose tissue, skeletal muscle, and heart.

Transport of Free Fatty Acids

• Free fatty acids are transported in the blood in combination with albumin.
• Normally, 3 free fatty acids combine with 1 albumin.
• In diabetes and starvation, 30 free fatty acids combine with 1 albumin.

Types of Lipoproteins

• Very low density lipoproteins (VLDLs): • High concentrations of triglycerides. • Moderate concentrations of cholesterol and phospholipids.
• Intermediate-density lipoproteins (IDLs): • Derived from VLDLs with removed triglycerides. • Increased concentrations of cholesterol and phospholipids.
• Low-density lipoproteins (LDLs): • Derived from IDLs with almost all triglycerides removed. • High concentration of cholesterol. • Moderately high concentration of phospholipids.
• High-density lipoproteins (HDLs): • High concentration of protein (about 50%). • Low concentrations of cholesterol and phospholipids.

Fat Deposits

• Two major tissues in the body store large quantities of fat: adipose tissue and the liver.

Adipose Tissue Functions

• Stores triglycerides
• Provides heat insulation for the body
• Secretes hormones, such as leptin and adiponectin

Liver Functions in Lipid Metabolism

• Degrades fatty acids into small compounds for energy
• Synthesizes triglycerides from carbohydrates and proteins
• Synthesizes other lipids, including cholesterol and phospholipids, from fatty acids

Triglyceride Accumulation in the Liver

• Occurs during early stages of starvation
• Occurs in diabetes mellitus
• Occurs in conditions where fat is used for energy instead of carbohydrates
• Also occurs in lipodystrophy, where large amounts of lipids are stored

Triglycerides for Energy: ATP Formation

• Triglycerides are broken down into fatty acids and glycerol through hydrolysis.
• Fatty acids enter the mitochondria to undergo further degradation.
• Beta-oxidation degrades fatty acids into acetyl-CoA, which is then oxidized.
• The oxidation of fatty acids yields large amounts of ATP.

Acetyl-CoA Conversion and Transportation

• Two acetyl-CoA molecules condense to form one molecule of acetoacetic acid.
• Acetoacetic acid is transported in the blood to cells throughout the body for energy production.
• Part of the acetoacetic acid is converted into β-hydroxybutyric acid.
• Minute quantities of acetoacetic acid are converted into acetone.

Hormonal Regulation of Fat Utilization

• Epinephrine and norepinephrine directly activate hormone-sensitive triglyceride lipase, stimulating fat utilization.
• Corticotropin and glucocorticoids have a ketogenic effect, promoting the breakdown of fat for energy production.
• Growth hormone has a similar, but weaker, effect compared to corticotropin and glucocorticoids in activating hormone-sensitive lipase.
• Thyroid hormone triggers rapid mobilization of fat, facilitating its utilization for energy purposes.