Lecture 12: Biosynthesis

Gluconeogenesis: Understand what gluconeogenesis is and its significance for polysaccharide synthesis.
Building Blocks: Identify the origins of building blocks for amino acids, nucleotides, and fatty acids.
Bacterial vs Archaeal Lipids: Discuss the differences and similarities between bacterial and archaeal lipids.

Role of Polysaccharides:
- Essential in many bacteria as part of the cell wall and as storage for carbon and energy.
Synthesis of Polysaccharides:
- In prokaryotes, polysaccharides are synthesized using activated forms of glucose:
- Uridine diphosphoglucose (UDPG): Precursor used for molecules in the cell wall.
- Adenosine diphosphoglucose (ADPG): Precursor for glycogen.
- The process involves adding activated glucose to a preexisting polymer fragment.

Definition: Gluconeogenesis is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates.
Importance:
- Cells growing on carbon sources other than glucose must synthesize glucose for energy and biosynthesis.
Pathway:
- Starts with phosphoenolpyruvate (PEP), an intermediate in glycolysis.
- It proceeds in the reverse direction of the glycolytic pathway to produce glucose.
PEP Synthesis:
- Can be synthesized from oxaloacetate, which is an intermediate in the citric acid cycle.

Significance: Pentoses are critical for synthesizing nucleic acids:
- Ribose: Used in the synthesis of RNA.
- Deoxyribose: Used in the synthesis of DNA.
Formation:
- Produced by removing one carbon atom from a hexose (C6 sugars).
Pathway for Pentose Production:
- Major source is the pentose phosphate pathway.
- Glucose is oxidized to produce:
- CO2, NADPH, and ribulose 5-phosphate (precursor for several pentoses).

Product:
- Produces NADPH, which is a crucial reductant used in various biosynthetic reactions (e.g., deoxyribonucleotide production, fatty acid biosynthesis).
Output in Carbohydrate Formation:
- Also creates sugars with 4-7 carbons, which can be converted into hexoses for metabolic purposes (catabolic or biosynthetic).

Complex Pathways:
- Amino acid biosynthesis often involves lengthy and multi-step pathways.
Families of Amino Acids:
- Grouped based on structural relatedness and shared biosynthetic steps.
Carbon Skeleton Sources:
- Derived from intermediates of glycolysis or the citric acid cycle.
Amino Group Source:
- Typically obtained from inorganic nitrogen, such as ammonia (NH3).
Incorporation of Ammonia:
- Facilitated by enzymes: glutamate dehydrogenase or glutamine synthetase.
- Transfer of amino groups is managed by transaminase or glutamate synthase.

Purines:
- Constructed atom by atom from various carbon and nitrogen sources.
- Purine Skeleton: Inosinic acid, which serves as the precursor to adenine and guanine.
- Once purines are attached to ribose (in triphosphate form), they are ready for incorporation into DNA or RNA.
Pyrimidines:
- Also synthesized from a variety of carbon and nitrogen sources.
- Orotic Acid: Serves as the precursor for thymine, cytosine, and uracil.
- Pyrimidine Skeleton: Uridylate, which is utilized to derive all pyrimidines.

Importance of Lipids:
- Serve as structural components of membranes and carbon/energy reserves.
Fatty Acids:
- Major lipid components. In Archaea, they do not have fatty acids in their membrane lipids but utilize isoprene.

Process:
- Synthesized 2 carbons at a time using acyl carrier proteins (ACPs).
- ACPs hold the growing fatty acid until it reaches its final length.
Malonyl-ACP Formation:
- Each incorporated C2 unit originates from the C3 compound malonate.
- The third carbon is released as CO2, while malonate is attached to the acyl carrier protein to create malonyl-ACP.

Initial Components:
- Acetyl-ACP and Malonyl-ACP are key substrates.
Reaction Flow:
- Each addition of an acetyl unit derives from malonyl-ACP.
Final Product: Palmitate (16 carbon atoms).

Species Variation: Fatty acid composition varies between different species and within the same organism depending on growth temperature.
- Lower Growth Temperatures: Associated with shorter and more unsaturated fatty acids.
- Higher Growth Temperatures: Characterized by longer and more saturated fatty acids.
Common Fatty Acids: Most commonly found in bacteria have chain lengths between C12-C20.
Types of Fatty Acids:
- Can be unsaturated, branched, or contain odd numbers of carbon atoms. Unsaturated fatty acids contain one or more double bonds in their hydrophobic portions formed by desaturation of saturated fatty acids.

Process of Lipid Assembly:
- In Bacteria and Eukarya, fatty acids add to a molecule of glycerol.
- For simple triglycerides, all three glycerol carbons are esterified with fatty acids.
- Complex lipids involve adding phosphate, ethanolamine, carbohydrate, or polar substances to one of the glycerol carbons.
Archaeal Membrane Lipids:
- Constructed from isoprene forming phytanyl (C15) or biphytanyl (C30) side chains instead of fatty acids.
- The glycerol backbone retains a polar group (sugar, phosphate, sulfate, organic compound).
Membrane Architecture:
- In all three domains, polar groups are critical for forming appropriate membrane architectures (hydrophobic interior, hydrophilic surfaces).

What is gluconeogenesis and why is it significant for polysaccharide synthesis?
Identify the activated forms of glucose used in prokaryotic polysaccharide synthesis. What are their specific roles?
Describe the pathway of gluconeogenesis starting from phosphoenolpyruvate (PEP). What is its importance in cellular metabolism?
Explain the significance of pentoses in nucleic acid synthesis and describe the formation process from hexoses.
What is the pentose phosphate pathway and what are its main products?
Outline the biosynthesis pathways of amino acids and indicate the sources of their carbon skeletons and amino groups.
Compare the biosynthesis of purines and pyrimidines, indicating their precursors and formation processes.
Discuss the importance of lipids in biological systems and describe the fatty acid biosynthesis process.
Differentiate between the variations in fatty acid composition at lower and higher growth temperatures. What implications does this have for organisms?
How are bacterial and archaeal membrane lipids structurally different?