Lipids and proteins Biochemistry test 4

Lipolysis and Oxidation of Glycerol

• Lipolysis involves the hydrolysis of triacylglycerols by lipases
• Hormone-sensitive lipase converts triacylglycerols into free fatty acids and monoacylglycerol.
• Monoacylglycerol is further hydrolyzed into fatty acid and glycerol

Oxidation of Glycerol

• Glycerol phosphorylation is catalyzed by glycerol kinase, forming glycerol-3-phosphate
• Glycerol-3-phosphate oxidation is catalyzed by glycerol phosphate dehydrogenase, which forms dihydroxyacetone phosphate and NADH
• Isomerization involves the interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate

Energy Yield of Glycerol Oxidation

• Glycerol converts to Glycerol-3-phosphate which yields -1 ATP
• Glycerol-3-phosphate converts to Dihydroxyacetone phosphate which yields +3 ATP from NADH
• Glyceraldehyde-3-phosphate converts to Pyruvate which yields +5 ATP from NADH and ATP
• Pyruvate converts to Acetyl-CoA which yields +3 ATP from NADH
• Acetyl-CoA oxidation in the Krebs cycle yields 12 ATP
• Total ATP yield: 22 ATP

Fatty Acids Oxidation Stages

• Stage 1 (β-oxidation) involves the oxidation of fatty acids to yield acetyl-CoA
• Stage 2 involves Acetyl-CoA entering the citric acid cycle, producing CO₂
• Stage 3 involves electrons from oxidation passing through the mitochondrial respiratory chain to generate ATP via oxidative phosphorylation.

Fatty Acid Activation and Transfer

• Fatty acids must be esterified to Coenzyme A (CoA) before oxidation
• Catalyst: Acyl-CoA Synthases (Thiokinases) catalyzes this reaction on the outer mitochondrial membrane

Fatty Acid Activation Reaction

• Fatty acid + ATP converts to Acyladenylate + PPi
• Acyladenylate + HS-CoA converts to Acyl-CoA + AMP

Carnitine Palmitoyl Transferases (CPT)

• Carnitine Palmitoyl Transferases (CPT) facilitates fatty acid transfer across the mitochondrial inner membrane
• CPT I transfers fatty acid from CoA to carnitine
• CPT II transfers fatty acid back to CoA inside the mitochondria for β-oxidation

β-Oxidation Fatty Acids Pathway

• β-Oxidation Fatty Acids Pathway occurs in the mitochondrial matrix

β-Oxidation Steps

• Acyl-CoA Dehydrogenase creates a double bond, reducing FAD to FADH₂
• Enoyl-CoA Hydratase hydrates the double bond, forming L-3-hydroxyacyl-CoA
• Hydroxyacyl-CoA Dehydrogenase oxidizes hydroxyl to a ketone, generating NADH
• β-Ketothiolase cleaves the bond, releasing acetyl-CoA and a shortened fatty acyl-CoA
• Overall, Fatty acyl-CoA+FAD+NAD++HS−CoA converts to Fatty acyl-CoA (2C less)+FADH2​+NADH Acetyl - CoA

Energy Yield of Fatty Acid Oxidation (Palmitic Acid Example)

• Palmitic Acid (C16) undergoes 7 cycles of β-oxidation, yielding 8 Acetyl-CoA
• ATP yield per cycle:
• 7 FADH₂ yields 10.5 ATP
• 7 NADH yields 17.5 ATP
• 8 Acetyl-CoA yields 80 ATP (via TCA cycle)
• Total ATP yield: ~106 ATP per palmitate

Ketone Bodies

• When glucose is scarce (starvation/diabetes), Acetyl-CoA accumulates due to low oxaloacetate levels (used in gluconeogenesis)
• Excess Acetyl-CoA is converted to ketone bodies in the liver

Ketone Body Formation

• Acetoacetyl-CoA thiolase: Condenses two Acetyl-CoA to Acetoacetyl-CoA
• HMG-CoA synthase: Adds another Acetyl-CoA to HMG-CoA
• HMG-CoA lyase: Cleaves HMG-CoA to Acetoacetate
• β-hydroxybutyrate dehydrogenase: Converts acetoacetate to β-hydroxybutyrate
• Acetoacetate decarboxylase: Converts acetoacetate to acetone, which is excreted in breath/urine

Fate of Ketone Bodies

• Ketone bodies are transported in the blood to the brain, muscles, and other tissues where they are reconverted into Acetyl-CoA for energy

Synthesis of Fatty Acid

• Synthesis of Fatty Acid occurs in the cytoplasm and requires ATP and NADPH

Synthesis of Fatty Acid Enzymes

• Acetyl-CoA carboxylase and Fatty Acid Synthase complex

Steps of Fatty Acid Synthesis

• Activation involves the conversion of Acetyl-CoA to Malonyl-CoA
• Elongation cycle: Condensation, Reduction, Dehydration, Reduction
• Fatty acids are synthesized 2 carbons at a time

Synthesis of Triacylglycerols and Phospholipids

• Enzymes: Glycerol-3-phosphate acyltransferase, Phosphatidate phosphatase
• Steps: Fatty acids are added to the glycerol backbone
• Reactions: Phospholipid precursors like phosphatidic acid are formed

Triacylglycerol and Phospholipid Synthesis

• Triacylglycerol synthesis involves Glycerol-3-phosphate + Fatty Acyl-CoA forming Phosphatidic acid, which then forms Diacylglycerol and finally Triacylglycerol
• Phospholipid synthesis involves similar steps but includes the addition of polar head groups like choline, ethanolamine, and serine

Amino Acid Metabolism

• Carbon skeletons of amino acids are converted into Glucose (gluconeogenesis), Ketone bodies, or TCA cycle intermediates

Metabolic Pathways for Amino Acid Carbon Skeletons

• Gluconeogenesis: Some amino acids are converted into intermediates of the TCA cycle and used for glucose production
• Ketogenesis: Some amino acids can form ketone bodies
• Energy production: Carbon skeletons enter the TCA cycle and undergo oxidation for ATP generation
• Fatty acid synthesis: Certain amino acids contribute to fatty acid biosynthesis

Main Metabolic Fates of Amino Acids

• Deamination and transamination

Deamination

• The removal of an amino group from amino acids, which produces ammonia and a corresponding keto acid

Transamination

• The transfer of an amino group from one amino acid to a keto acid, forming a new amino acid and a different keto acid
• Key enzymes include aminotransferases (e.g., ALT, AST)

Urea Cycle

• The urea cycle occurs primarily in the liver to detoxify ammonia, which is produced from amino acid metabolism.

Steps and Enzymes

• Carbamoyl phosphate synthetase I converts ammonia and bicarbonate to carbamoyl phosphate
• Ornithine transcarbamylase forms citrulline from ornithine and carbamoyl phosphate
• Argininosuccinate synthetase adds aspartate to citrulline to form argininosuccinate
• Argininosuccinate lyase cleaves argininosuccinate into arginine and fumarate
• Arginase converts arginine into urea and ornithine

Products of Urea Cycle

• Urea (excreted in urine) and fumarate (which enters the TCA cycle)

Conversion of Amino Acids to Specialized Products

• Amino acids serve as precursors for various specialized biomolecules

Neurotransmitters

• Tyrosine converts to Dopamine, Epinephrine, and Norepinephrine
• Tryptophan converts to Serotonin

Hormones

• Tyrosine converts to Thyroid hormones

Other Biomolecules

• Glycine is a precursor for heme in Porphyrins (heme synthesis)
• Arginine, glycine, and methionine contribute to creatine biosynthesis
• Glutathione is derived from glutamate, cysteine, and glycine