Sebenta de Bioquímica 2024/25 MIM UFP PDF

Sebenta de Bioquímica Paola Tuerlinckx 2024/25 MIM UFP Structural Biochemistry Carbohydrates Carbohydrates are one of the main macronutrients, alongside proteins and fats, that are vital for providing energy to the body. They are made up of carbon, hydrogen, and oxygen and are found in a wide rang...

Sebenta de Bioquímica Paola Tuerlinckx 2024/25 MIM UFP Structural Biochemistry Carbohydrates Carbohydrates are one of the main macronutrients, alongside proteins and fats, that are vital for providing energy to the body. They are made up of carbon, hydrogen, and oxygen and are found in a wide range of foods. The structure of carbohydrates is based on carbon (C), hydrogen (H), and oxygen (O) atoms, typically in the ratio of 1:2:1. Carbohydrates can vary significantly in size and complexity, ranging from simple sugars to long, complex molecules. Their structure can be broken down into three main types: 1. Monosaccharides (Simple Sugars):  Structure: Monosaccharides are the simplest form of carbohydrates and consist of a single sugar molecule. Common monosaccharides include: Glucose (or dextrose) → Preferred energy source of brain cells or cells without mitochondria (erythrocytes) →The main sources are starch and the disaccharides lactose, maltose and sucrose Fructose (or levulose or fruit sugar) → The male reproductive system uses fructose (incorporated into the semen) → Exists in large quantities in fruit. Also present in vegetables and honey Galactose → Required in the synthesis of biomolecules →lactose, glycolipids , phospholipids… Ring Structure: In solution, most monosaccharides exist as ring structures rather than straight chains. Glucose, for example, forms a six-membered ring. Carbohydrates can be classified in ketoses and aldoses, the upper part is different. - → Classified according to the number of carbon Optical Isomers (Enantiomers): Non-superimposable mirror images (e.g., D-glucose vs. L-glucose).  Epimers: Diastereomers that differ at only one specific chiral center (e.g., D-glucose vs. D-galactose at C- Diastereomers: Stereoisomers that are not mirror images and differ at one or more (but not all) chiral centers (e.g., D-glucose vs. D-mannose). Prof examples →D-ribose and L-ribose, and D-arabinose and L-arabinose are enantiomers →D-ribose and D-arabinose are diastereomers →D-glucose and D-galactose are epimers 1. Fischer Projection: A two-dimensional representation of the linear (open-chain) form of carbohydrates, showing the spatial arrangement of atoms around chiral centers. Vertical lines represent bonds going into the plane, while horizontal lines represent bonds coming out of the plane. 2. Haworth Projection: A three-dimensional representation of the cyclic (ring) form of carbohydrates, commonly used for sugars like glucose. It shows the spatial arrangement of atoms in the ring, with the oxygen atom as part of the ring structure and substituents (like hydroxyl groups) positioned above or below the ring.  α- and β-Anomers in Haworth projection: The two anomeric forms are labeled α and β based on the orientation of the hydroxyl group (-OH) on the anomeric carbon: α-Anomer: o The hydroxyl group attached to the anomeric carbon is on the opposite side of the ring relative to the CH₂OH group (carbon 6) in the D-sugar form. In glucose, this means the -OH group is positioned below the plane of the ring. o Example: In α-D-glucopyranose, the -OH on the anomeric carbon (C1) is down in the Haworth projection. β-Anomer: o The hydroxyl group attached to the anomeric carbon is on the same side of the ring relative to the CH₂OH group (carbon 6) in the D-sugar form. This means the -OH group is positioned above the plane of the ring. o Example: In β-D-glucopyranose, the -OH on the anomeric carbon (C1) is up in the Haworth projection. Mutarotation in when alfa or beta forms interconvert when dissolved in water Oxidation in the presence of oxidizing agents, metal ions (Cu2+), and certain enzymes.  →Oxidation of an aldehyde group gives rise to an aldonic acid →Oxidation of a terminal CH2OH gives rise to uronic acid → Oxidation of an aldehyde and CH2OH gives rise to a All monosaccharides are reducing sugars → Can be oxidized by weak oxidizing agents (e.g. Benedict's: Copper (II), sulfate in sodium carbonate and sodium citrate solution.) Reduction of aldehyde and ketone groups of monosaccharides gives rise to sugar alcohols (alditols) - Isomerization involves an intramolecular change of a hydrogen atom and a reattachment of the doble bond. Important derived monossacharides( a prof não especificou as funções de cada mas acho que percebemos melhor assim) 1. Uronic Acids: Definition: Uronic acids are derived from monosaccharides by the oxidation of the terminal hydroxyl group (-CH₂OH) on the last carbon, converting it into a carboxyl group (-COOH). Function: Uronic acids play crucial roles in the formation of glycosaminoglycans (components of connective tissue), and they are involved in detoxification processes, as they can combine with toxins for excretion. Examples: o D-Glucuronic acid: Formed by the oxidation of D-glucose at the C6 position. It is involved in the detoxification of substances in the liver and plays a role in forming glycosaminoglycans like hyaluronic acid and chondroitin sulfate.  o L-Iduronic acid: A stereoisomer of glucuronic acid found in glycosaminoglycans, especially in heparin and dermatan sulfate, important for anticoagulation and wound healing. o Galacturonic acid: Derived from D-galactose, it is a key component of pectin, a structural polysaccharide found in plant cell walls. 2. Amino Sugars: Definition: Amino sugars (or hexosamines) are derived monosaccharides where one hydroxyl group (usually on the C2 position) is replaced by an amino group (-NH₂). These sugars are essential in the synthesis of glycoproteins, glycolipids, and proteoglycans. Function: Amino sugars are crucial components of glycosaminoglycans, which are vital for the structure of connective tissues, as well as in the formation of bacterial cell walls and viral coatings. Examples: o D-Glucosamine: Formed by replacing the hydroxyl group at C2 of D-glucose with an amino group. It is a major component of chitin (insect exoskeletons and fungal cell walls) and glycosaminoglycans like hyaluronic acid. o D-Galactosamine: Derived from D-galactose with an amino group at C2. It is found in chondroitin sulfate, important for cartilage structure and function. o N-Acetylglucosamine (GlcNAc): A glucosamine derivative where the amino group at C2 is acetylated (linked to an acetyl group, -COCH₃). It is a building block of hyaluronic acid and is a part of the bacterial cell wall component peptidoglycan. 3. Deoxysugars: Definition: Deoxysugars are monosaccharides where one or more hydroxyl groups (-OH) have been replaced by hydrogen atoms (-H), "deoxygenating" the sugar. These sugars are vital components in various biomolecules, including DNA. Function: Deoxysugars are essential in the structure of important molecules like deoxyribonucleic acid (DNA) and in certain antibiotics and glycosides. Examples: o 2-Deoxyribose: The most important deoxysugar, it is the sugar component of DNA, where the hydroxyl group at C2 of ribose is replaced by a hydrogen atom. This small structural change gives DNA greater stability compared to RNA. o L-Fucose: A deoxy sugar derived from D-galactose (6-deoxy-L-galactose), found in glycoproteins and glycolipids, particularly in blood group antigens. o Rhamnose: A 6-deoxy-L-mannose, which is found in plant glycosides and bacterial cell walls. 2. Disaccharides:  Structure: Disaccharides are formed when two monosaccharide molecules are linked together via a glycosidic bond, which is a covalent bond between the carbon atoms of the sugar molecules. Examples include: o Sucrose: Glucose + Fructose (table sugar) α(1→2) glycosidic bond o Lactose: Glucose + Galactose (found in milk) β(1→4) glycosidic bond. o Maltose: Glucose + Glucose (found in malt products) Disaccharide with one (1,4) glycosidic bond. o Frutose.: is a disaccharide composed of fructose and glucose α(1→2) glycosidic bond. Glycosidic Bond: This bond is created by a dehydration reaction (removal of water) between two hydroxyl groups (-OH) on adjacent monosaccharides. 3. Oligosaccharides Short chains of monosaccharides (3-10 sugars) attached to proteins or lipids, functioning in cell recognition, signalling, and structural roles. N-Linked Oligosaccharides: Oligosaccharides attached to the nitrogen atom of the amino acid asparagine in proteins, following the sequence Asn-X-Ser/Thr. O-Linked Oligosaccharides: Oligosaccharides attached to the oxygen atom of the hydroxyl group of the amino acids serine or threonine in proteins. 4. Polysaccharides (Complex Carbohydrates): Structure: Polysaccharides are long chains of monosaccharide units, typically glucose, linked by glycosidic bonds. The number of monosaccharides in a polysaccharide can range from a few to thousands. The functions of this kind of carbohydrates are essentially energy reserve and structural material. Polysaccharides can be: o Linear: The chains of sugar molecules are straight. o Branched: The chains have multiple offshoots. Examples of polysaccharides include: o Starch: A storage form of glucose in plants. It consists of two types of polysaccharides—amylose (linear) and amylopectin (branched). Amylose- unbranched chains of D-glucose, linked by (1,4) glycosidic bonds.  Amylopectin -Branched polymer of D-glucose, with (1,4) and (1,6) glycosidic bonds. o Glycogen: The storage form of glucose in animals, similar to amylopectin but more highly branched. High abundance in liver and muscle cells. →D-glucose branched polymer, with (1,4) and (1,6) glycosidic bonds → The branch points of (1,6) occur every 4 glucose residues within the molecule and every 8-12 outside the molecule. o Cellulose: A structural polysaccharide found in the cell walls of plants. It consists of linear chains of glucose but with different glycosidic bonds, making it indigestible by humans. → Composed of D-glucoses linked by (1,4) glycosidic bonds. o Chitin: Found in the exoskeletons of insects and crustaceans, chitin is a polysaccharide made of modified glucose molecules. Lipids Lipids are a diverse group of hydrophobic or amphipathic organic compounds that are insoluble in water but soluble in nonpolar solvents (e.g., ether, chloroform). They play critical roles in biological systems, especially in energy storage, cell membrane structure, and signaling pathways. 1. Energy Storage: o Lipids, particularly triglycerides, are highly efficient energy storage molecules. They store more than twice the energy per gram as carbohydrates and are broken down through β-oxidation to release ATP. 2. Cell Membrane Structure: o Lipids, especially phospholipids and cholesterol, form the lipid bilayer of cellular membranes, providing a barrier that separates the cell from its environment while allowing selective permeability. 3. Signaling Molecules: o Lipids act as important signaling molecules in various pathways. Steroid hormones, eicosanoids (derived from arachidonic acid), and other lipid-based molecules regulate inflammation, metabolism, immune responses, and more. 4. Insulation and Protection: o In animals, lipids (in the form of adipose tissue) provide thermal insulation and protect vital organs by cushioning them. 5. Absorption of Fat-Soluble Vitamins: o Lipids are essential for the absorption of fat-soluble vitamins (A, D, E, K) in the intestine, as these vitamins are solubilized in dietary fats. Classification of Lipids: Lipids can be broadly classified into several categories based on their structure and function: 1. Fatty Acids: o Structure: Long hydrocarbon chains with a terminal carboxyl group (-COOH). o Types: ▪ Saturated fatty acids (no double bonds). ▪ Unsaturated fatty acids (one or more double bonds). o Functions: Serve as building blocks for more complex lipids; energy storage molecules; precursors for signaling molecules like prostaglandins. Cannot be synthesized → They have to be obtained through diet (vegetable oils, nuts, seeds, fish, etc.) → Linoleic acid (18:29,12 or 18:2 -6) →Linolenic acid(18:3 -3) 2. Triacylglycerols (Triglycerides): o Structure: Composed of three fatty acids esterified to a glycerol backbone. o Function: Major form of energy storage in animals; stored in adipose tissue. Upon hydrolysis, they release fatty acids, which can be oxidized to produce energy. Storage of fatty acids. 3. Phospholipids:  o Structure: Composed of two fatty acids, a glycerol backbone, and a phosphate group (which can be linked to other functional groups like choline, serine, etc.). o Function: Major components of cell membranes (forming lipid bilayers). They are amphipathic, with hydrophobic tails and hydrophilic heads, enabling the formation of bilayer membranes that are critical for cell compartmentalization. 4. Steroids: o Structure: Based on a four-ring carbon structure (steroid nucleus). o Examples: Cholesterol, steroid hormones (e.g., testosterone, estrogen). o Functions: Cholesterol is an essential component of cell membranes, modulating fluidity; steroids act as hormones involved in a variety of physiological functions like growth, metabolism, and reproduction. 5. Glycolipids: o Structure: Lipids covalently bonded to carbohydrate groups thought an o-glycosidic bond.. o Function: Important components of the cell membrane, particularly in the nervous system; involved in cell recognition and signalling. 6. Sphingolipids: o Structure: Built around a sphingosine backbone rather than glycerol. o Function: Key components of cell membranes, particularly in nerve cells (myelin sheath). They play roles in signal transmission and cell recognition. → Contain long chains of amino-alcohols (sphingosine) → The nucleus is ceramide(precursors of glycolipids), an amide derived fatty acid of sphingosine  7. Waxes ( Como curiosidade): o Structure: Esters of long-chain fatty acids with long-chain alcohols. o Function: Serve as protective coatings in plants and animals (e.g., waxy cuticle on leaves, ear wax in mammals). Functions of Lipids in Biological Systems: Lipid Metabolism (vamos ver melhor nas páginas em frente): Synthesis: Lipogenesis is the process by which fatty acids and triglycerides are synthesized, primarily in the liver. Breakdown: Lipids are broken down via β-oxidation, producing acetyl-CoA, which enters the citric acid cycle for ATP production. Lipid metabolism is tightly regulated by hormones like insulin (stimulates fat storage) and glucagon (stimulates fat breakdown). Amino Acids Amino acids are organic molecules that serve as the building blocks of proteins. Each amino acid contains a central carbon atom (α-carbon) bonded to four different groups: an amino group (-NH₂), a carboxyl group (- COOH), a hydrogen atom, and a distinctive side chain (R group) that determines the properties and function of each amino acid. After the formation of peptides bonds we can have a polypeptide and a protein. pH = 7 → The carboxyl group is in the conjugate base form and the amine group is in the acid conjugate form. 1. Nonpolar, Hydrophobic Amino Acids These amino acids are nonpolar and avoid water: Glycine (Gly)  Alanine (Ala) Valine (Val) Leucine (Leu) Isoleucine (Ile) Methionine (Met) Proline (Pro) Phenylalanine (Phe) Tryptophan (Trp) Mnemonic: "GLAd VALiant LEaders In METal PROtect PHEarless TRoops." GLY = Glycine ALA = Alanine VAL = Valine LEU = Leucine ILE = Isoleucine MET = Methionine PRO = Proline PHE = Phenylalanine TRP = Tryptophan 2. Polar, Uncharged Amino Acids These amino acids are polar but not charged: Serine (Ser) Threonine (Thr) Asparagine (Asn) Glutamine (Gln) Cysteine (Cys) Tyrosine (Tyr) Mnemonic: "SERiously THRilled ASNice GLamorous CYSters TYRlessly."  SER = Serine THR = Threonine ASN = Asparagine GLN = Glutamine CYS = Cysteine TYR = Tyrosine 3. Acidic (Negatively Charged) Amino Acids These are acidic amino acids that are negatively charged: Aspartic Acid (Asp) Glutamic Acid (Glu) Mnemonic: "ASPiring GLUes are Acidic." ASP = Aspartic Acid GLU = Glutamic Acid 4. Basic (Positively Charged) Amino Acids These amino acids are positively charged: Lysine (Lys) Arginine (Arg) Histidine (His) Mnemonic: "LYRics ARGue HIStory." LYS = Lysine ARG = Arginine HIS = Histidine 5. Aromatic Amino Acids These amino acids have aromatic ring structures: Phenylalanine (Phe)  Tyrosine (Tyr) Tryptophan (Trp) Mnemonic: "PHE TYRannosaurus TRiumphs." PHE = Phenylalanine TYR = Tyrosine TRP = Tryptophan Phosphorylation Phosphorylation is the addition of a phosphate group (PO₄³⁻) to amino acids, which is essential for regulating protein function, signaling pathways, and enzyme activity. Amino acids modified: o Serine (Ser) o Threonine (Thr) o Tyrosine (Tyr) Glycosylation Glycosylation is the attachment of carbohydrate (sugar) molecules to amino acids, which is crucial for protein folding, stability, and cell-cell recognition. Amino acids modified: o Asparagine (Asn) (N-linked glycosylation) o Serine (Ser) and Threonine (Thr) (O-linked glycosylation Hydroxylation Hydroxylation is the addition of a hydroxyl group (OH) to amino acids, playing a critical role in stabilizing the structure of proteins like collagen. Amino acids modified: o Proline (Pro) o Lysine (Lys) Carboxylation Carboxylation is the addition of a carboxyl group (-COOH) to amino acids, which is important for blood clotting proteins. Amino acid modified: o Glutamate (Glu) Enzymes Enzymes are biological catalysts that accelerate chemical reactions in living organisms without being consumed in the process. They have specific active sites where substrates bind, leading to the formation of an enzyme- substrate complex. This facilitates the conversion of substrates into products by lowering the activation energy requ ired for the reaction. A catalyst is a property of the enzymes that increases the rate of reaction without changing it , it also decreases the energy of reaction. The enzyme work by a system of active site. Each type enzyme molecule contains an unique binding surface. Some enzymes only with cofator. This is a non-protein component , that could be for instance ions such as MG2+ and Zn2+.  Some enzymes only are presents if we have in our body some vitramines. Different tipes of enzymes Hydrolases: Enzymes that catalyze the hydrolysis of various bonds. For example, amylase breaks down starch into sugars Oxidoreductases: Enzymes that catalyze oxidation- reduction reactions. For example, dehydrogenases transfer electrons from one molecule to another. Transferases: Enzymes that transfer functional groups from one molecule to another. For example, kinases transfer phosphate groups. Isomerases: Enzymes that catalyze the rearrangement of atoms within a molecule(geometrical or structural changes). For example, phosphoglucose isomerase converts glucose-6-phosphate to fructose-6-phosphate. Ligases: Enzymes that join two molecules together using ATP. For example, DNA ligase joins DNA fragments together. Lyases: Enzymes that catalyze the breaking of various chemical bond ( C-C ,C-O ,C-N ) s by means other than hydrolysis and oxidation. It works as a atom elemination.For example, decarboxylases remove carboxyl groups from molecules. It generates doble bonds.. Michaelis-Menten Kinetics One of the foundational models in enzyme kinetics is the Michaelis-Menten equation, which describes how the reaction velocity (rate) of an enzyme-catalyzed reaction depends on the concentration of the substrate. The model assumes that the enzyme-substrate complex (ES) forms rapidly and reversibly, and that the reaction proceeds as follows: E+S↔ES→E+P Where: E is the enzyme. S is the substrate. ES is the enzyme-substrate complex. P is the product. The Michaelis-Menten equation is expressed as: Where: v is the reaction velocity. Vmax is the maximum reaction velocity when the enzyme is saturated with the substrate. [S] is the substrate concentration. Km (Michaelis constant) is the substrate concentration at which the reaction velocity is half of Vmax. It reflects the enzyme's affinity for the substrate—a lower Km indicates higher affinity. The Michaelis-Menten equation assumes steady-state conditions, where the formation and breakdown of the enzyme-substrate complex occur at the same rate. It is most applicable to simple enzyme-catalyzed reactions. Key Concepts in Michaelis-Menten Kinetics Vmax: The maximum rate of the reaction, representing the point at which all enzyme active sites are saturated with substrate. Km: Represents the substrate concentration at which the reaction velocity is 50% of Vmax. A low Km value suggests the enzyme has a high affinity for the substrate, while a high Km value indicates lower affinity. Turnover number (kcat): The number of substrate molecules converted into product by a single enzyme molecule per second under saturated substrate conditions. Lineweaver-Burk Plot (Double-Reciprocal Plot) The Lineweaver-Burk plot is a linearized version of the Michaelis-Menten equation and is used to determine enzyme kinetics parameters such as Vmax and Km more precisely. It’s based on the reciprocal form of the Michaelis-Menten equation: In this plot: Advantages of the Lineweaver-Burk plot include its ability to present data in a linear form, which can help visualize enzyme inhibition types, such as competitive, non-competitive, and uncompetitive inhibition. However, this plot can distort data at low substrate concentrations. Enzyme Inhibition Types Competitive Inhibition: The inhibitor binds to the active site of the enzyme, preventing the substrate from binding. It increases Km (lower affinity) but does not affect Vmax. In Lineweaver-Burk plots, competitive inhibitors shift the curve to the right. Non-Competitive Inhibition: The inhibitor binds to a site other than the active site (allosteric site), reducing the enzyme's ability to catalyze reactions. It decreases Vmax but does not change Km. Lineweaver-Burk plots show a change in slope with the same x-intercept. Allosteric enzymes are enzymes whose activity is regulated by the binding of molecules at specific sites other than the active site. These sites are called allosteric sites.  1. Acid-Base Catalysis In acid-base catalysis, a proton (H⁺) is transferred either to or from the reactants during the reaction, stabilizing transition states and facilitating bond cleavage or formation. Acid Catalysis: The catalyst donates a proton to a reactant, making it more electrophilic and prone to nucleophilic attack. Acidic amino acids like aspartate or glutamate often serve this function in enzymes. Base Catalysis: The catalyst accepts a proton from a reactant, increasing its nucleophilicity. Amino acids like histidine are common proton acceptors in enzyme active sites. Example: In the enzyme ribonuclease, histidine acts as both a general acid and a general base, donating and accepting protons at different steps of the RNA hydrolysis reaction. 2. Covalent Catalysis In covalent catalysis, the enzyme forms a transient covalent bond with the substrate, creating a more reactive intermediate. This mechanism involves nucleophilic attack by a functional group in the enzyme (such as the hydroxyl group of a serine or the sulfhydryl group of a cysteine) on the substrate, temporarily forming a covalent bond. The catalyst provides a nucleophile (e.g., an amino acid side chain in an enzyme) that forms an unstable covalent intermediate, which is then broken down in a subsequent step. This mechanism is common in proteases such as serine proteases, where a serine residue attacks the peptide bond. Example: In chymotrypsin, a serine residue in the active site forms a covalent bond with the substrate during peptide bond hydrolysis. The formation of this covalent intermediate lowers the activation energy of the reaction. 3. Metal Ion Catalysis In metal ion catalysis, metal ions participate directly in the catalytic process, often stabilizing negative charges, activating water molecules, or serving as electrophilic catalysts. Metal ions can also help in orienting the substrate properly within the active site. Stabilization of Charges: Metal ions like Zn²⁺ or Mg²⁺ stabilize the negative charges on reaction intermediates.  Water Activation: Metal ions can also help in the activation of water molecules, making them more nucleophilic for hydrolytic reactions. Example: The enzyme carbonic anhydrase uses a zinc ion (Zn²⁺) to activate a water molecule, facilitating the conversion of carbon dioxide to bicarbonate. The metal ion also stabilizes the negative charge in the transition state. Enzymes are really sensitive to PH, Temperatures and other mechanical and quimical effects. Amino acid metabolism I and II NONESSENCIAL amino acids are those who can be made by the body. Complete proteins : sufficient amounts of EAA Plant proteins- Do not contain 1 or more EAA Serine , cysteine and glycine can be obtained from phosphoglycerate…( we have to know which molecule synthetised the different aminoacids) We are in a nitrogen balance (amino acids because they are the molecules simplest with nitrogen) when the imput of n equals the loss Positive N balance- N impute the loss Negative N balance- When individual cannot replace losses with food sources How can amino acids be obtained and eliminate: Amino acids can be used in the synthesis of glucose , urea and ketone bodies and non-protein nitrogenous tissues constituents How can molecules go to the cell: Glutathione-It’s constituent by glutamyl, cysteine and glycine -it’s a three peptide. It has thiol group -SH present in cysteine. (GSH) Functions: -Involvement DNA and RNA synthetises -GSH acts as a reducing agent because it works in the synthesis of eicosanoids -protects cell from radiation -promotes the transport of amino acids 1. Synthesis of Glutathione (GSH) Glutathione is a tripeptide made from three amino acids: glutamate, cysteine, and glycine. Its synthesis occurs in two steps: Step 1: Glutamate and cysteine are joined together via the enzyme glutamate-cysteine ligase (GCL) (also known as gamma-glutamylcysteine synthetase). This forms gamma- glutamylcysteine. This is the rate-limiting step of glutathione synthesis and is tightly regulated by feedback inhibition from glutathione. Step 2: The enzyme glutathione synthetase catalyzes the addition of glycine to gamma- glutamylcysteine, forming glutathione (GSH). 2. Role of Gamma-Glutamyl Transpeptidase (GGT) Once glutathione is synthesized, it can participate in amino acid transport. This process is driven by the enzyme gamma-glutamyl transpeptidase (GGT), which is located on the outer surface of the plasma membrane. GGT transfers the gamma-glutamyl group from glutathione to an amino acid that needs to be transported into the cell. The reaction produces a gamma-glutamyl-amino acid and leaves behind cysteinylglycine. The cysteinylglycine is hydrolyzed by a dipeptidase to yield free cysteine and glycine, which can re-enter the cycle for further glutathione synthesis. 3. Amino Acid Transport and Recycling The gamma-glutamyl-amino acid complex formed by GGT allows the amino acid to enter the cell. Inside the cell, the enzyme gamma-glutamyl cyclotransferase breaks the bond, releasing the free amino acid and converting the gamma-glutamyl group to 5-oxoproline (pyroglutamate). 5-oxoproline is then converted back to glutamate by the enzyme 5-oxoprolinase, completing the cycle. This recycling is crucial because the released glutamate can be reused to synthesize more glutathione. The free amino acid is now available for various cellular processes, such as protein synthesis, energy production, or metabolic pathways. 4. Re-synthesis of Glutathione Once the amino acid is transported into the cell and glutamate is regenerated, the process starts over with the synthesis of new glutathione. Transaminases- normally glutamate is always present and alfa ketoglutarate too 1- The alfa amino acid that donate the alfa amine group 2- Alfa keto acid that accepts the alfa amine group We must know these pairs: -alfa-ketoglutarate/glutamate -Oxaloacetate/aspartate -Pyruvate/alanine We need to know the names of ALT(alanine aminotransferase), GPT(glutamate-pyruvate transaminase),AST( aspartate aminotransferase),GOT( glutamate-oxaloacetate transaminase) Oxidative deamination- we have the release of ammonia (NH4+/NH3), the presence of ammonia can cause mental retardation because it is really toxic for our brain Glutamate reacts with ammonia and creates glutamine Group amide  We can obtain ATP from amino acid, that’s why we do oxidative transamination. Brain cells convert toxin NH4+ into glutamine ----transport to the liver-----there it forms glutamate and NH4+. The urea cycle (hepatocytes) removes 90% of unnecessary N Urea diffuses and go into the bloodstream and its eliminate in the urine via the kidneys. Regulation of the urea cycle Nh4+ is toxic so our body has to take it off. Some hormones like glucagon and glucocorticoids are involving in altering enzymes synthesis rates. Like carbamoyl phosphate synthetase I is activated by N-acetylglutamate. Amino Acid Catabolism Initial Step: The catabolism of amino acids begins with the removal of the amine group. Utilization of Byproducts: The resulting compounds can be used to synthesize fatty acids, produce glucose, or generate energy. Glucogenic Amino Acids Degraded to form pyruvate or intermediates of the Krebs cycle. These intermediates can then be used in gluconeogenesis to produce glucose. Ketogenic Amino Acids Broken down into acetyl-CoA or acetoacetyl-CoA. These molecules can be converted into fatty acids or ketone bodies. We have to know every amino acid Carbohydrate metabolism I Metabolic Pathways: Pathways consist of sequential reactions leading from a starting molecule to a final product, typically with a loss of free energy. These pathways can be reversible or irreversible, depending on cellular needs and enzymes involved. Cells cannot usually store must substances of a metabolic pathway, so the pay a price (ATP) to be able to store energy in form of glycogen or triacylglycerols Many intermediated cannot go away of the cell Energy Storage and Utilization: ATP is the primary energy currency of the cell. Cells store energy in glycogen or triacylglycerols, though storage capacity is limited. During fasting, glucose is rapidly used, and gluconeogenesis enables glucose production from non-carbohydrate sources. Glucose Uptake and Transport: Glucose enters cells via insulin-dependent transport (e.g., muscle, adipocytes) or insulin-independent transport (e.g., liver, brain). The concentration gradient between blood and intracellular glucose drives uptake. Glycolysis: In anaerobic conditions, glycolysis converts glucose to lactate, producing 2 ATP molecules. In aerobic conditions, glycolysis produces pyruvate, which can enter the Krebs cycle via acetyl-CoA formation. Mature red blood cells rely solely on glycolysis for ATP production due to the absence of mitochondria. Tissue-Specific Metabolism:  The brain and CNS preferentially use glucose, oxidizing it to pyruvate and subsequently to CO₂ for energy. Adipose tissue uses glucose for glycogen, lipid synthesis, and energy production. During exercise, muscles may produce lactate to sustain ATP production under limited oxygen. Liver Metabolism: The liver plays a central role in maintaining glucose levels, using pathways like glycolysis, glycogen synthesis, and gluconeogenesis. It can synthesize glucose from lactate via gluconeogenesis and regulate glucose levels in the blood. He liver has two enzymes capable of catalysing the formation of glucose -6-P from glucose and ATP, hexokinase and glucokinase. Regulation and Control: Cells balance NAD+ and NADH to sustain glycolysis, especially under high- energy demand. Phosphoenolpyruvate and other intermediates are crucial for energy transfer within cells. Some chemical Inhibitors of glycolysis Iodoacetate and Iodoacetamide: These chemicals inhibit the enzyme glyceraldehyde-3-phosphate dehydrogenase by binding to its active site. This blocks the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, halting glycolysis in its middle stages. Fluoride: Inhibits the enzyme enolase, which converts 2-phosphoglycerate to phosphoenolpyruvate. This prevents the subsequent production of pyruvate and ATP in later steps.  Arsenate: Mimics inorganic phosphate and interferes with reactions where phosphate is normally added. It disrupts ATP formation by uncoupling reactions, especially at the glyceraldehyde-3-phosphate dehydrogenase step, resulting in reduced ATP yield. 2-Deoxyglucose: This glucose analog is phosphorylated by hexokinase but cannot proceed further in glycolysis. It effectively "traps" phosphate and stalls glycolysis, leading to decreased glucose utilization. Mercury and Heavy Metals: These metals can bind to enzymes like glyceraldehyde-3-phosphate dehydrogenase, inhibiting their activity and stopping glycolysis. Anaplerotic Reactions: These reactions replenish intermediates in metabolic cycles, such as the Krebs cycle, ensuring the continuity of energy production processes. Pentoses Phosphate pathway and gluconeogenesis Pentose phosphate pathway The big objective of the pentose Phosphate pathway is to produce NADPH which is a reducing agent essential for biosynthetic reactions , such as fatty acid and nucleotide synthesis. Gluconeogenesis Gluconeogenesis is the metabolic pathway that synthesizes glucose from non- carbohydrate precursors. This process is crucial for maintaining blood glucose levels during fasting, intense exercise, or when dietary carbohydrates are insufficient. Here are key points about gluconeogenesis: 1. Main Function: To produce glucose for tissues that rely on it as a primary energy source, such as the brain, red blood cells, and renal medulla. 2. Primary Location: Gluconeogenesis primarily occurs in the liver, with a smaller amount taking place in the kidneys, especially during prolonged fasting. 3. Precursors for Glucose Production: o Lactate: Produced by anaerobic glycolysis in muscles and red blood cells; converted to glucose in the liver (Cori cycle). o Amino Acids: Especially alanine and glutamine, derived from muscle protein breakdown, can be converted to intermediates that feed into gluconeogenesis. o Glycerol: Released from triglyceride breakdown in adipose tissue, converted to glucose in the liver. 4. Pathway and Enzymes: o Gluconeogenesis shares several steps with glycolysis but bypasses the three irreversible steps in glycolysis using unique enzymes: ▪ Pyruvate Carboxylase and PEP Carboxykinase bypass pyruvate kinase. ▪ Fructose-1,6-Bisphosphatase bypasses phosphofructokinase. ▪ Glucose-6-Phosphatase bypasses hexokinase/glucokinase. o These bypass reactions ensure that gluconeogenesis is a one-way process, distinct from glycolysis. 5. Regulation: o Gluconeogenesis is regulated by hormonal signals like glucagon (stimulating gluconeogenesis) and insulin (inhibiting gluconeogenesis). o It is also influenced by substrate availability and energy status, with high levels of ATP favoring gluconeogenesis. lide 16 - Glucose-6-Phosphate: Glucose-6-phosphate (G6P) is a key intermediate that cannot exit the cell. In the liver, G6P can be used for energy, stored as glycogen, or converted to free glucose for release into the bloodstream, helping regulate blood glucose levels. Slide 17 - Coordination of Cytosolic and Mitochondrial Enzymes: Gluconeogenesis involves enzymes in both the cytosol and mitochondria, requiring a coordinated transfer of intermediates between these compartments for efficient glucose synthesis. Slide 18 - Glucose Release and Metabolic Balance: Produced glucose-6-phosphate can be used for immediate energy, glycogen synthesis, or, in the liver, exported to the blood. This process in the liver is essential for maintaining overall metabolic stability Synthesis of Glucose from Glycerol (Slide 19): Glycerol is converted by glycerol kinase into glycerol-3-phosphate. This intermediate is then converted into dihydroxyacetone phosphate (DHAP) by glycerol-3-phosphate dehydrogenase, allowing it to enter the gluconeogenesis pathway. Gluconeogenesis from Odd-Chain Fatty Acids (Slide 20): Odd-chain fatty acids yield propionyl-CoA, which is converted into succinyl- CoA. Succinyl-CoA enters the Krebs cycle and eventually forms oxaloacetate, a precursor for gluconeogenesis.  Hexose Interconversion (Slide 21): This involves transformations among hexose sugars, facilitating various metabolic needs of the cell. Conversion of Mannose (Slide 23): Mannose is phosphorylated by hexokinase to form mannose-6-phosphate. Mannose phosphate isomerase converts mannose-6-phosphate to fructose-6- phosphate, which can then enter glycolysis or gluconeogenesis. Hormonal Regulation of Gluconeogenesis (Slide 24): Hormones like glucagon stimulate gluconeogenesis, while insulin inhibits it, maintaining blood glucose balance according to the body's needs. Impact of Ethanol on Gluconeogenesis (Slide 25): Ethanol metabolism in the liver produces excess NADH. High NADH levels shift pyruvate and oxaloacetate to lactate and malate, respectively, reducing the availability of these key intermediates for gluconeogenesis. This can inhibit gluconeogenesis and contribute to hypoglycemia in individuals consuming large amounts of alcohol. Kreb Cycle Oxidative Phosphorylation Result in the potential synthesis of 2 ATP Result in the potential synthesis of 3 ATP The redution of oxygen involves the formation of intermediate species potencially harmfull. The superoxide anion and hydrogen peroxide are highly reactive species that, if accumulated, can damage cells. Glycogen Metabolism OMAGODDD love this image The start of de novo glycogen synthesis seems to occur through a derivative of glycogenin, a self- glucosylating protein that provides a high molecular weight substrate adequate to the action of glycogen synthase. After the maturation of the molecule of glycogen, the bond glycogenin-glycogen is broken down Glucose Uptake Mechanism: Liver Cells: The liver uses an insulin-independent glucose transporter (GLUT2) that allows glucose to enter the liver cells freely, depending on blood glucose levels. This uptake helps the  liver to manage blood glucose by either storing excess glucose as glycogen or releasing it when needed. Muscle Cells: Muscle cells use an insulin-dependent glucose transporter (GLUT4). Insulin signals the muscle cells to take in glucose from the blood, which is especially important after meals when blood glucose levels are high. Glycogen Synthesis (Glycogenesis): In both liver and muscle cells, excess glucose is stored as glycogen, a branched polymer of glucose, to provide a readily available energy source. Key Steps in Glycogenesis: o Glucose-6-Phosphate Formation: Once glucose enters the cell, it is phosphorylated to glucose-6-phosphate (G6P), trapping it inside the cell. o Isomerization to Glucose-1-Phosphate: G6P is converted into glucose-1-phosphate (G1P) by the enzyme phosphoglucomutase. o Activation by UDP-Glucose: G1P is activated by binding with uridine diphosphate (UDP), forming UDP-glucose. o Glycogen Synthase: UDP-glucose is added to the growing glycogen chain by glycogen synthase, which is the primary enzyme for glycogen synthesis. o Branching Enzyme: Glycogen branching enzyme introduces branches in the glycogen molecule, increasing its solubility and making it easier to mobilize glucose quickly. Insulin promotes glucose uptake and glycogen synthesis in both liver and muscle by activating enzymes involved in glycogenesis. Glucagon (in the liver) and epinephrine (in the liver and muscle) stimulate glycogen breakdown (glycogenolysis) to increase glucose availability during low blood glucose or stress. Besides the hormonal control, glycogen synthesis is also influenced by high concentrations of free glucose in liver. High levels of glucose have a negative effect in the activity of the enzyme phosphorylase and stimulates the inactivation of this enzyme by a phosphatase. MOD B. LIPID METABOLISM I Lipid Class Structure Functions Fatty Hydrocarbon chain with a carboxyl Energy source, membrane component, precursor Acids group for signaling Acylglycerols Glycerol backbone with 1-3 fatty acids Energy storage, insulation, metabolic fuel Sphingosine backbone with fatty acid Membrane structure, signaling, nerve Sphingolipids (ceramide) insulation Four-ring steroid structure Membrane fluidity, hormone production, bile acid Sterols (cholesterol, etc.) synthesis Glycerol, two fatty acids, phosphate Membrane structure, signal transduction, Phospholipids group, polar head lung surfactant Ketone Small molecules: acetoacetate, beta- Alternative energy source during fasting or Bodies hydroxybutyrate low carbohydrate intake The process by which fatty acids are used to produce energy is called fatty acid oxidation, primarily occurring in the mitochondria of cells. This process involves several stages and pathways, with the ultimate goal of generating ATP, the main energy currency of cells. Lipolysis: In response to hormonal signals (like glucagon and epinephrine), stored triglycerides in adipose tissue are hydrolyzed by hormone-sensitive lipase, releasing free fatty acids (FFAs) and glycerol into the bloodstream. Fatty Acid Activation & Transport: FFAs are taken up by cells (e.g., muscle, liver) and activated in the cytoplasm to fatty acyl-CoA using ATP. Long-chain fatty acids are transported into the mitochondria via the carnitine shuttle (CPT I, translocase, CPT II).  Beta-Oxidation: In the mitochondrial matrix, beta-oxidation occurs. Fatty acyl-CoA is progressively shortened by 2-carbon units with each cycle, producing: Acetyl-CoA (which enters the Krebs cycle), NADH and FADH₂ (which feed into the electron transport chain). ATP Production: Acetyl-CoA enters the TCA cycle, generating more NADH and FADH₂. NADH and FADH₂ drive ATP synthesis via the electron transport chain and oxidative phosphorylation.  Degradation of odd fatty acids is done in the same way, with production of acetyl-CoA, and in the last cycle remains one molecule of three carbons, propionyl CoA. Vit. B12 Propionyl-CoA can be converted into succinyl-CoA that enters the Krebs cycle. Pernious anemia - Results from deficiency in vitamin B12 - Leads to the acumulation of methylmalonyl-CoA -Leads to the acumulation of odd chain fatty acids The oxidation of unsaturated fatty acids follows a similar process to that of saturated fatty acids, using the beta-oxidation pathway to break down the fatty acid chain and produce energy. However, unsaturated fatty acids have one or more double bonds, which require additional enzymatic steps to rearrange these bonds for proper degradation. Ketone bodies During prolonged fasting or low carbohydrate intake, the body increases fat breakdown for energy, releasing large amounts of acetyl-CoA from fatty acid oxidation. However, without sufficient oxaloacetate (which is diverted for gluconeogenesis to produce glucose), acetyl-CoA cannot enter the Krebs cycle in the liver. The liver converts the excess acetyl-CoA into ketone bodies through a process called ketogenesis. Certain organs (heart and skeletal muscle) can use ketone bodies as an energy source in normal conditions. During fasting periods, the brain uses ketone bodies as energy source. Since the liver does not have  ketoacyl-CoA transferase, it cannot use ketone bodies as energy source Fatty acid Synthesis Acetyl-CoA formed in the mitochondria from pyruvate is required for the synthesis of fatty acids that occurs in the cytoplasm. Acetyl-CoA cannot go out of the mitochondria, requiring to be transformed into a transportable substance and later recovered in the cytosol, with the return of the transporter component to the mitochondria NADPH is required for the reduction reactions of fatty acid synthesis. It is essential the presence of enough NADPH stores in the cytoplasm to support the synthesis of fatty acids and other reactions of synthesis. The main source is the pentose phosphate pathway, another source is the conversion of malate into pyruvate catalyzed by the malic enzyme. In the ER the sequence of reactions is similar to the ones catalyzed in the cytosol by fatty acid synthase, with malonyl-CoA acting as a source of two carbon units and NADPH as the reducing power. The reactions seem to be catalyzed by different enzymes. In most tissues, except brain, palmitic acid is converted exclusively to stearic acid. Thioesterase II is an enzyme expressed in the mammary tissue during lactation period. It interacts with fatty acid synthase and stops the synthesis of long chain fatty acids, being produced in relative abundance, medium chain fatty acids, having 8 to 12 carbons. For the introduction of double bonds in long chain fatty acids, it is required a flux of electrons and molecular oxygen. This sequence of reactions occurs in the endoplasmic reticulum. The specific enzyme delta-9-desaturase puts a double bond in carbon 9 (C9) of the fatty acid How it is regulated ? Citrate is an allosteric effector of acetyl-CoA carboxylase, the main regulatory point of the pathway. Malonyl-CoA is an inhibitor of carnitine acyl transferase I. Some diseases Von Gierke’s Disease (Type I): Caused by a deficiency of glucose-6-phosphatase in the liver, intestines, and kidneys. Leads to symptoms like fasting hypoglycemia, lactic acidemia, hyperlipidemia, and hyperuricemia. Managing the disease includes frequent carbohydrate intake to prevent hypoglycemia, even overnight. Pompe’s Disease (Type II): Caused by a deficiency of α-1,4-glucosidase in lysosomes, resulting in glycogen buildup. Affected patients, often children, may experience cardiomegaly and face early death due to heart failure. Cori’s Disease (Type III): Due to a debranching enzyme deficiency, which impairs glycogen degradation.  Leads to hepatomegaly (enlarged liver) that may decrease with age, and symptoms similar to a milder form of Von Gierke’s disease. McArdle’s Disease (Type V): Caused by a lack of muscle glycogen phosphorylase. Patients experience muscle cramps and inability to perform intense exercise due to a lack of accessible glycogen. May lead to muscle damage, with elevated creatine phosphokinase, aldolase, and myoglobin levels in the blood. Lactic Acidosis: Occurs when lactate accumulates due to low oxygen levels in tissues, causing a drop in pH and potential metabolic acidosis. Characterized by high lactate levels (>5mM), reduced pH, and low bicarbonate in the blood. Pyruvate Kinase Deficiency: Causes hemolytic anemia as mature red blood cells depend on glycolysis for ATP production, essential for maintaining cell shape and function. This deficiency affects Na+/K+ ATPase pumps, impairing the red blood cells' ability to maintain their biconcave shape and leading to hemolysis. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: Patients with this enzyme deficiency may develop hemolytic anemia when exposed to certain drugs (e.g., sulfa or anti-malarial drugs). G6PD deficiency impairs the pentose phosphate pathway, reducing NADPH needed for maintaining glutathione levels and protecting red blood cells from oxidative stress. Cholesterol Synthesis Cholesteryl esters represent the form of store of cholesterol derived from the diet or from biosynthetic sources. These esters can be synthetized in the cytosol of most cells or in plasma. We just need to know what is produced. Fasting Lipogenesis: A diet rich in excess carbohydrates and fats can stimulate the storage of fat through lipogenesis, converting these macronutrients into triglycerides stored in adipose tissue. Lipolysis: During calorie restriction or low carb/high-fat diets, stored fat is broken down into fatty acids for energy, especially as the body shifts to using fat as a primary fuel source. Carbohydrate Metabolism: Initially, glycolysis and glycogenolysis supply glucose.  Gluconeogenesis (from amino acids and glycerol) becomes crucial as glycogen depletes. Fat Metabolism: Lipolysis breaks down triglycerides into fatty acids for energy. Beta-oxidation and ketogenesis convert fatty acids into ketones, an alternative energy source for the brain and muscles. Protein Metabolism: In early fasting, amino acids from muscle breakdown support gluconeogenesis. Later, the body shifts to conserve muscle mass by relying more on fats and ketones. Fasting Stages: Stage 1 (0-12 hours): Glycogen is used for glucose, with fatty acids powering muscles. Stage 2 (12-48 hours): Fat breakdown increases, with ketones rising as a primary fuel source. Stage 3 (Several days): Muscle preservation intensifies; metabolic rate drops to conserve energy. Final Stage: Severe muscle and organ degradation if fasting persists. Hormonal Changes: Insulin decreases, and glucagon rises, promoting fat and glycogen breakdown.  Growth hormone protects muscle, while cortisol supports gluconeogenesis. Dietary Interventions: Strategies like caloric restriction and ketogenic diets mimic fasting benefits and may support metabolic health. CONCLUSAO Glycolysis: Converts glucose to pyruvate, generating 2 ATP and 2 NADH per glucose molecule, providing quick energy, especially under anaerobic conditions. Glycogenolysis: The breakdown of glycogen (stored glucose) in the liver and muscles, releasing glucose to maintain blood sugar or supply muscle energy. Glycogenesis: The synthesis of glycogen from glucose, storing excess glucose in liver and muscle for future energy needs. Gluconeogenesis: The formation of glucose from non-carbohydrate sources (e.g., amino acids, glycerol) primarily in the liver, maintaining blood glucose during fasting. Krebs Cycle (Citric Acid Cycle): Occurs in the mitochondria, oxidizing acetyl-CoA to produce NADH, FADH₂, and ATP, with CO₂ as a byproduct, central to energy production. Pentose Phosphate Pathway: Produces NADPH (for biosynthesis and antioxidant defense) and ribose-5-phosphate (for nucleotide synthesis) without ATP generation. Electron Transport Chain (ETC): Located in the mitochondrial membrane, it uses electrons from NADH and FADH₂ to generate ATP through oxidative phosphorylation. Ketone Body Production (Ketogenesis): In the liver, fatty acids are converted to ketone bodies (e.g., acetoacetate, beta-hydroxybutyrate) during low glucose states, providing an alternative energy source, especially for the brain. Urea Cycle: Converts ammonia (a toxic byproduct of amino acid breakdown) into urea in the liver, which is then excreted by the kidneys.  Fatty Acid Synthesis: Occurs in the cytoplasm, where acetyl-CoA is converted to fatty acids, primarily for energy storage or membrane production. Cholesterol Synthesis: Primarily in the liver, acetyl-CoA is converted to cholesterol, a vital component for cell membranes and a precursor for steroid hormones and bile acids. Central Hub: Metabolism 1. Carbohydrate Metabolism o Glycolysis ▪ Breaks down glucose to pyruvate. ▪ Produces ATP and NADH. ▪ Connects to: ▪ Krebs Cycle (pyruvate enters as acetyl-CoA). ▪ Pentose Phosphate Pathway (alternate glucose use for NADPH). ▪ Gluconeogenesis (reversal during fasting). o Glycogenolysis ▪ Breaks down glycogen to release glucose. ▪ Connects to: ▪ Glycolysis (glucose produced enters glycolysis). ▪ Gluconeogenesis (replenishes blood glucose in fasting). o Glycogenesis ▪ Synthesizes glycogen from glucose. ▪ Connects to: ▪ Glycolysis (when energy is needed, glycogen is broken down). ▪ Glycogenolysis (provides glucose for energy in fasting). 2. Energy Production Pathways o Krebs Cycle (Citric Acid Cycle) ▪ Oxidizes acetyl-CoA, producing NADH, FADH₂, ATP, and CO₂. ▪ Connects to: ▪ Electron Transport Chain (uses NADH and FADH₂ for ATP). ▪ Glycolysis (supplies acetyl-CoA).  ▪ Beta-Oxidation (fatty acids provide acetyl-CoA). o Electron Transport Chain (ETC) ▪ Uses NADH and FADH₂ to generate ATP. ▪ Connects to: ▪ Krebs Cycle (source of NADH/FADH₂). ▪ Beta-Oxidation (provides FADH₂ and NADH from fatty acid breakdown). ▪ Ketone Body Production (alternative energy source if ETC glucose is limited). o Pentose Phosphate Pathway ▪ Produces NADPH and ribose-5-phosphate. ▪ Connects to: ▪ Fatty Acid Synthesis (NADPH needed). ▪ Cholesterol Synthesis (requires NADPH). 3. Lipid Metabolism o Beta-Oxidation ▪ Breaks down fatty acids to acetyl-CoA. ▪ Connects to: ▪ Krebs Cycle (acetyl-CoA entry for energy). ▪ Ketone Body Production (when acetyl-CoA exceeds Krebs needs). o Ketone Body Production (Ketogenesis) ▪ Produces ketone bodies from excess acetyl-CoA. ▪ Connects to: ▪ Brain/Muscle (use ketones as fuel). ▪ Krebs Cycle (alternate pathway for acetyl-CoA). o Fatty Acid Synthesis ▪ Builds fatty acids from acetyl-CoA and NADPH. ▪ Connects to: ▪ Pentose Phosphate Pathway (source of NADPH).  ▪ Glycolysis (provides acetyl-CoA from glucose). 4. Amino Acid & Protein Metabolism o Urea Cycle ▪ Converts ammonia to urea for safe excretion. ▪ Connects to: ▪ Amino Acid Catabolism (source of ammonia). ▪ Gluconeogenesis (amino acids as substrates). o Gluconeogenesis ▪ Generates glucose from non-carb sources (amino acids, glycerol). ▪ Connects to: ▪ Amino Acid Catabolism (provides substrates). ▪ Glycolysis (provides substrates during fasting). 5. Sterol Metabolism o Cholesterol Synthesis ▪ Synthesizes cholesterol from acetyl-CoA. ▪ Connects to: ▪ Fatty Acid Synthesis (shares acetyl-CoA pool). ▪ Pentose Phosphate Pathway (provides NADPH).