A&P Metabolism 1: Cellular Respiration and Metabolism

• Metabolism encompasses all chemical reactions in the body
• Metabolism is the sum of catabolism and anabolism

Catabolism

• Breaks down complex molecules into simpler ones
• Is an exergonic reaction that releases energy stored in molecules
• Is required for converting substrates to a 2-carbon molecule used by mitochondria to produce ATP

Anabolism

• Combines simple molecules into complex ones
• Is an endergonic reaction that requires energy
• Is required for replacing membranes, organelles, enzymes, and structural proteins

Cellular Catabolism

• Also known as aerobic metabolism or cellular respiration
• Requires oxygen and occurs in the mitochondria
• Captures 40% of energy to convert ADP to ATP, used for anabolism and other functions
• The remaining 60% of energy escapes as heat

Adenosine Triphosphate (ATP)

• ATP stores energy in the bonds between phosphate groups
• ATP is created in exergonic reactions: ADP + energy yields ATP
• ATP creation is demonstrated in catabolic reactions, like glycolysis
• Anabolic reactions require ATP; for example, glycogenesis
• ATP is the energy used in endergonic reactions and is the "energy currency" of the body

Utilization of Nutrients

• Nutrients come from diet and reserves

Utilization of Nutrient Reserves

• Reserves are mobilized when absorption across the digestive tract is insufficient to maintain normal nutrient levels
• Cells break down triglycerides and glycogen into fatty acids and glucose
• Adipocytes break down triglycerides to release fatty acids
• Skeletal muscle cells break down contractile proteins to potentially release amino acids

ATP Reserves

• Reserves are stocked when absorption by the digestive tract exceeds immediate nutrient needs
• Liver cells store triglycerides and glycogen
• Adipocytes convert excess fatty acids to triglycerides
• Skeletal muscles build glycogen reserves and use amino acids to increase numbers of myofibrils

Location of Resources

• Cells continuously absorb and catabolize glucose
• Nervous tissue requires a continuous glucose supply
• Other tissues can switch to fatty acid or amino acid catabolism during starvation, conserving glucose for nervous tissue; ketones can also be used

Oxidation-Reduction (REDOX) Reactions

• Oxidation and reduction are always paired
• Oxidation is the loss of electrons from a molecule, reducing its potential energy; involves loss of hydrogen atoms (dehydrogenation)
• Reduction is the gain of electrons by a molecule, increasing its potential energy
• When a molecule is oxidized, it often loses electrons (in the form of hydrogen atoms)
• Liberated hydrogen atoms must be accepted by another molecule to be reduced

Key Coenzymes

• NAD+ is reduced to NADH + H+
• FAD is reduced to FADH2
• These coenzymes are not proteins and facilitate greater ATP production

Glucose Metabolism

• Oxidation of glucose occurs during metabolism
• Glucose (C6H12O6) is split into 2 pyruvate molecules (C3H4O3) during glycolysis
• Glucose molecules lose 4 hydrogen atoms
• The 4 hydrogen molecules are then accepted by NAD+ to become NADH/ H+

Mechanisms of ATP Generation

Substrate-level Phosphorylation

• Direct transfer of a high-energy phosphate group from an intermediate to ADP
• Occurs in glycolysis, citric acid cycle, and phosphocreatine.

Oxidative Phosphorylation

• Electrons are removed and passed through an electron transport chain to oxygen

Carbohydrate Metabolism

• Glucose, the breakdown product of carbohydrates, is absorbed in the small intestine
• Glucose is the body's preferred energy source, most other saccharides are also converted to glucose

Reason for Glucose Preference

• Glucose is small, soluble, and easily distributed throughout body fluids

GLUT Transporters

• GLUT transporters bring glucose into the cell via facilitated diffusion
• Insulin increases the expression of these transporters in the plasma membrane, accelerating glucose entry into cells
• Glucose is trapped in cells after being phosphorylated

Fate of Glucose

• The fate of glucose depends on the needs of body cells

• ATP production is always the first step if immediate energy is needed

• Glycogen synthesis combines glucose molecules to form glycogen

• Amino acid synthesis is used to form proteins

• Triglyceride synthesis is the last resort when other storage is full, converting remaining glucose to fats

Glycolysis Steps

• Formation of acetyl coenzyme A
• Citric Acid Cycle reactions
• Electron transport chain reactions

Main Stages of Glucose Catabolism

• There are 4 steps in the utilization of a glucose molecule
• Glycolysis
• Formation of acetyl coenzyme A
• Citric Acid Cycle reactions (Krebs cycle)
• Electron transport chain reactions

Anaerobic vs Aerobic Respiration

• Anaerobic respiration does not require oxygen and involves substrate-level phosphorylation
• Aerobic respiration requires oxygen and involves Krebs Cycle and oxidative phosphorylation

Glycolysis

• Cellular respiration always begins with glycolysis - First step
• Glycolysis begins with one glucose molecule
• Splits the 6-carbon glucose into two 3-carbon pyruvic acid molecules
• Occurs in the cytosol
• Glycolysis consists of 10 reactions
• Uses 2 ATP but generates 4 ATP ( a net gain of 2 ATP) and 2 NADH
• The first 5 steps use ATP and increase the potential energy of the molecules
• The final 5 steps generate 4 ATP

End Products of Glycolysis

• Two pyruvate molecules
• 4 ATP molecules (2 net ATP)
• 2 NADH

Rate-Limiting Step

• Is the slowest, irreversible step in a pathway
• Determines the rate at which the entire pathway is carried out
• Phosphofructokinase drives the rate-limiting step

Fate of Pyruvate

• Its fate depends on oxygen availability; if oxygen is scarce (anaerobic), it is reduced to lactic acid
• Under aerobic conditions, pyruvic acid is converted to acetyl coenzyme A and enters the Citric Acid Cycle
• If oxygen is available, it will go to the ETC to create more ATP

Formation of Acetyl Coenzyme A

• The second step in cellular respiration

• A transitional step between glycolysis and the Krebs cycle

• Each pyruvic acid is converted to a 2-carbon acetyl group, releasing one molecule of CO2 as a waste product

• Pyruvic acid enters the mitochondria first and then is converted to acetyl coenzyme A

• It takes place in the mitochondrial matrix

• Each pyruvic acid also loses 2 hydrogen atoms

• NAD + is ultimately reduced to NADH/H+

• Pyruvate Dehydrogenase breaks apart to create 2 CO2 and 2 NADH

Byproduct Per Molecule

• 2 CO2 which is waste product
• 2 NADH which will go to ETC to create more ATP

The Cori Cycle

• If oxygen is scarce (anaerobic), it is reduced to lactic acid
• 2 pyruvic acid + 2NADH+2H+→ 2 Lactic acid and 2 NAD+
• Once lactic acid is produced, it quickly diffuses out of the cell and enters the blood
• Hepatocytes can convert lactic acid to glucose
• Other oxygenated tissue can reduce lactic acid back into pyruvate to be used

Key Facts About Glucose Transport

• Glucose enters the cell through GLUT transporters via facilitated diffusion
• Once glucose enters the cell, it is immediately phosphorylated, trapping it inside

Glycolysis starting and end points

• A glucose molecules starts glycolysis
• Two pyruvate molecules are the end product of glycolysis

Net Gain

• 2 net ATP is a net gain

Citric Acid Cycle

• the cycle is also known as Kreb's Cycle or TCA Cycle
• In anaerobic conditions glucose can be replenished, but not sustainably with net loss.
• This process requires oxygen and is an aerobic respiration
• Takes place inside the matrix of the mitocondria
• A series of redox reactions transfer energy to coenzymes
• The overall function removes hydrogen atoms from specific organic molecules and transfers them to coenzymes

Final Products

• Transfers Hydrogen atoms
• 2 CO2 (4 CO2 per glucose molecule: waste product)
• 3 NADH (6 NADH per glucose molecule: will go to ETC to create more ATP)
• 1 FADH2 (2 FADH2 per glucose molecule: will go to ETC to create more ATP)
• 1 ATP (2 ATP per glucose molecule)

Electron Transport Chain (ETC)

• A series of electron carriers called cytochromes in the inner mitochondrial membrane
• Electrons from NADH and FADH2 oxidize
• Each electron carrier has an increasing affinity for electrons down the chain
• As electrons pass, energy is released
• Stored energy in electrochemical gradient creates ATP
• Final electron acceptor is 02 and water formed

Functions

• Produces >90% of ATP used in the body

• Lack of oxygen stops the ETC

• Blocking cytochromes stops the ETC as well

• Example, poisons such as cyanide can block cytochromes

• With no ETC, the citric acid cycle stops

• Cells die from lack of ATP

• Proton-motive force: is the gradient

• Chemiosmosis: movement of hydrogen ions back into the matrix

• ATP synthase: uses the movement of energy to generate ATP

• The complex is bound to the inner mitochondrial membrane

Total ATP

• NADH: yields 8 ATP
• FADH2 : yields 2 ATP
• 4 ATP total from Glycolysis and Citric Acid Cycle
• The total ATP is 32 ATP per glucose molecule
• In an anaerobic environment, pyruvic acid reduces to form lactic acid and diffuses into the blood to travel to the liver

Acetyl CoA

• Acetyl CoA is formed in the Mitochondrial matrix
• Reduced coenzymes that carry potential energy

Citric Acid Cycle

• The CO2 that it produces diffuses out of mitochondria, then the plasma membrane, into the blood where it is transported to the lungs to be exhaled

Explore the processes of cellular respiration and metabolism. Key topics include coenzymes, glycolysis, ATP generation, and the role of catabolism. Understand how glucose is utilized and how energy is balanced within a cell.