Carbohydrate Metabolism

Glycolysis

Glycolysis is a central metabolic pathway that converts glucose into pyruvate, generating ATP and NADH. It occurs in the cytoplasm of cells and is the first step in cellular respiration.

• Phosphorylated Intermediates: Almost every intermediate in glycolysis contains a phosphate group. This prevents intermediates from diffusing out of the cell and helps conserve metabolic energy.

• Energy Investment vs. Energy Generation: Glycolysis consists of two phases:

  • Energy Investment Phase: Consumes 2 ATP per glucose molecule to phosphorylate intermediates.

  • Energy Generation Phase: Produces 4 ATP and 2 NADH per glucose molecule.

• Fate of Pyruvate: Pyruvate can be metabolized in several ways:

  • Converted to acetyl-CoA for entry into the TCA (Krebs) cycle (aerobic conditions).

  • Reduced to lactate (anaerobic conditions in animals).

  • Converted to ethanol and CO2 (alcoholic fermentation in yeast).

Example: In muscle cells during intense exercise, pyruvate is reduced to lactate to regenerate NAD+ for continued glycolysis.

Gluconeogenesis

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors, such as amino acids, lactate, and glycerol. It is essentially the reverse of glycolysis, with some bypass steps.

• Occurs mainly in the liver.

• Activated during fasting or starvation to maintain blood glucose levels.

Glycogenesis and Glycogenolysis

• Glycogenesis: The synthesis of glycogen from glucose for energy storage.

• Glycogenolysis: The breakdown of glycogen to release glucose when energy is needed.

Hormonal Regulation: Insulin vs. Glucagon

• Insulin: Promotes glucose uptake and storage (glycogenesis); activated in the fed state.

• Glucagon: Stimulates glycogen breakdown and gluconeogenesis; activated during fasting or low blood glucose.

Starvation Response: During starvation, the body increases gluconeogenesis and mobilizes fat stores for energy.

Lipid Metabolism

Digestion and Transport

• Lipids are digested in the small intestine and transported in the blood as lipoproteins (e.g., chylomicrons, VLDL, LDL, HDL).

Triacylglycerol Metabolism

• Mobilization: Stored triacylglycerols are hydrolyzed to release fatty acids and glycerol.

• Fate of Glycerol: Glycerol can enter glycolysis or gluconeogenesis.

β-Oxidation

β-Oxidation is the catabolic process by which fatty acids are broken down in the mitochondria to generate acetyl-CoA, NADH, and FADH2.

• Each cycle removes two carbons from the fatty acid chain as acetyl-CoA.

Lipogenesis

Lipogenesis is the anabolic process of synthesizing fatty acids from acetyl-CoA, primarily in the liver and adipose tissue.

Ketone Bodies and Ketogenesis

• Ketone Bodies: Water-soluble molecules (acetoacetate, β-hydroxybutyrate, acetone) produced from acetyl-CoA during prolonged fasting or carbohydrate restriction.

• Ketogenesis: The process of synthesizing ketone bodies in the liver.

Nucleic Acids and Genetics

Components of Nucleotides

• Phosphate group

• Pentose sugar: Ribose (RNA) or deoxyribose (DNA)

• Nitrogenous base: Purines (adenine, guanine) or pyrimidines (cytosine, thymine, uracil)

Nucleic Acids: DNA and RNA

• DNA: Double-stranded helix; stores genetic information.

• RNA: Single-stranded; involved in protein synthesis and gene regulation.

• Complementary Base Pairs: A-T (DNA), A-U (RNA), G-C.

DNA Replication

• Process by which DNA makes a copy of itself before cell division.

Types of RNA

• rRNA: Ribosomal RNA, forms ribosomes.

• mRNA: Messenger RNA, carries genetic code from DNA to ribosome.

• tRNA: Transfer RNA, brings amino acids to ribosome during translation.

Transcription and Translation

• Transcription: Synthesis of RNA from a DNA template (hnRNA processed to mRNA).

• Translation: Synthesis of proteins from mRNA template using ribosomes and tRNA.

• Codons: Triplets of nucleotides in mRNA that specify amino acids.

Mutations

• Point Mutations: Single nucleotide changes.

• Insertion/Deletion Mutations: Addition or loss of nucleotides, potentially causing frameshifts.

• Results: Can lead to altered or nonfunctional proteins.

Protein and Amino Acid Metabolism

Digestion

• Proteins are broken down into amino acids by proteases in the digestive tract.

Amino Acid Metabolism

• Transamination: Transfer of an amino group from one amino acid to a keto acid to form new amino acids.

• Oxidative Deamination: Removal of an amino group as ammonia, usually from glutamate.

• Urea Cycle: Converts toxic ammonia to urea for excretion.

• Glucogenic vs. Ketogenic Amino Acids:

  • Glucogenic: Amino acids that can be converted to glucose.

  • Ketogenic: Amino acids that can be converted to ketone bodies.

• Essential vs. Nonessential Amino Acids:

  • Essential: Must be obtained from the diet.

  • Nonessential: Can be synthesized by the body.

• Reductive Amination: Synthesis of amino acids by adding an amino group to a keto acid.

• Synthesis from Related Amino Acids: Some amino acids are synthesized from others (e.g., glutamine from glutamate, asparagine from aspartate, tyrosine from phenylalanine).

Metabolic Pathways: General Considerations

• Purpose: Each pathway serves a specific function (e.g., energy production, biosynthesis).

• Regulation: Pathways are activated or deactivated based on cellular needs and hormonal signals.

• Anabolic vs. Catabolic: Anabolic pathways build molecules; catabolic pathways break them down.

• Location: Pathways occur in specific cellular compartments (e.g., cytoplasm, mitochondria).

• Interconnections: Pathways are interconnected; intermediates can feed into multiple pathways.

• ATP Yield: Know the net ATP produced or consumed in each pathway.

ATP Equivalents from Electron Carriers

• 1 NADH → 2.5 ATP

• 1 FADH2 → 1.5 ATP

• 1 GTP → 1 ATP

Analyzing Reaction Steps

• Identify reactants and products.

• Determine the coenzyme involved (e.g., NAD+, FAD, CoA).

• Classify the enzyme (e.g., oxidoreductase, transferase, hydrolase).

• Describe the reaction type (e.g., oxidation, reduction, hydrolysis, condensation).

Key Equations

• ATP yield from NADH:

• ATP yield from FADH2:

• ATP yield from GTP: