BIOCHEM 192 mod 3 - Metabolism

Explain why ATP is considered the central energy intermediate of the cell.

ATP hydrolysis is energetically favourable, so it is paired with other reactions that are not energetically favourable, ATP hydrolysis joining a reaction decreases its Gibbs free energy so it is less than zero, thus the reaction is spontaneous. ATP is therefore used all over the body to drive cell function.

Describe the classes of macronutrients that provide energy (fuel molecules).

Carbohydrates: Are digested into monosaccharides

Lipids: are digested into fatty acids

Proteins: Are digested into amino acids

Nucleic acids: are digested into Nucleotides

Carbs, Lipids, Proteins also have uses as structural proteins 

What are the characteristics of coenzymes that are important in the metabolic pathways.

Some minerals are used as simple coenzymes. More complex ones are often made for Vitamins. The three important ones for metabolism are NAD, FAD, coA. NAD and FAD are redox reactants, so they are reduced/oxidised to balance out the reduction/oxidation done on the substrate.

In the metabolic pathways, energy is released from fuel molecules primarily by what kind of reactions.

Redox reactions, as H+ ions are removed from the substrate and exited into the intermembrane space of the mitochondria.

Briefly describe how carbohydrates are broken down during digestion to give glucose.

First complex carbohydrates are hydrolysed into glucose by amylase which breaks the glycosidic bonds, forming disaccharides which are broken into glucose by more specific enzyme e.g. sucrase for sucrose.

From there glycolysis takes place, breaking down glucose for ATP synthesis.

Describe how glucose is transported across membranes using the gut epithelial cells as an example.

Glucose is polar so does not pass through the cell membrane, so requires active transport proteins or faciliated diffusion.

Gut epithelial cells: SGLT: Symport of glucose and Na+ into the epithelial cell - glucose up concentration gradient - Na+ down concentration gradient

Na+ concentration increases in the cell

Describe why certain cell types depend or prefer to use glucose as a fuel molecule.

The brain uses glucose for ATP synthesis since using fatty acids requires oxygen which could risk depriving neurons of oxygen, and FA  ATP synthesis is too slow for sustaining the brain adequately.
Also eyes, white muscle tissue, 

State the key features of glycolysis

Conversion of one molecule of glucose (6 carbons) to two molecules of pyruvate (3 carbons) Energy conserved in ATP and NADH (detail tomorrow) Pyruvate may be further metabolised aerobically or anaerobically

Describe the overall organization of glycolysis and where energy is either invested, captured and released as heat.

Reaction 1: Glucose + ATP ➔ glucose-6-phosphate + ADP ΔGo’= -17 kJ/mol

: Invested some energy to get the molecule into the right form.

Glucose is then split into two pyruvate molecules, releasing some energy. The rest of the reactions happen to two pyruvate molecules.

Understand how energy coupling can be used to drive unfavourable reactions in metabolic pathways.

Combining a favourable reaction like ATP hydrolysis with an unfavourable one sums the two reactions’ Gibbs free energy value, so ATP hydrolysis can push the combined reaction to be favourable.

Describe how the events in key reactions of glycolysis lead to the conversion or capture of energy.

• ATP invested: Hexokinase + phosphofructokinase use ATP to activate glucose.

• NADH made: Glyceraldehyde-3-phosphate is oxidized → NAD⁺ reduced to NADH (captures electrons).

• ATP generated: High-energy intermediates (1,3-BPG, PEP) donate phosphate to ADP by substrate-level phosphorylation → ATP profit.

• Net gain: 2 ATP + 2 NADH per glucose, with energy also released as heat

Describe the fates of pyruvate under different conditions and why lactate is made under anaerobic conditions.

• Aerobic: Pyruvate → acetyl-CoA → citric acid cycle + oxidative phosphorylation (max ATP).

• Anaerobic (animals): Pyruvate → lactate (via lactate dehydrogenase).

• Why lactate? Regenerates NAD⁺ from NADH so glycolysis can keep making ATP when oxygen is low

Describe the basic structure of a fatty acid and triacylglycerol (TAG)

Fatty Acids have long carbon chains with a Carboxyl group at the end.
Triacylglycerol consists of a glycerol group bound to three fatty acids.

Describe the role of pancreatic lipase and bile salts in the digestion of triacylglycerol.

Lipases: enzymes that hydrolyses TAGs to release FFA. Pancreatic lipase in small intestine hydrolyses fatty acids at positions 1 and 3, giving 2 FFA molecules and monoacylglycerol. 

Bile acids are produced from cholesterol in the liver. They have a cholesterol ring and hydroxyl or carboxyl groups. They surround FFA’s in a cell environment, hydrophobic ring pointing in, hydrophilic groups pointed outward.

Describe lipoproteins and explain their role in the transport of fatty acids around the body.

Lipoproteins acts as carriers for TAGS or FA;s by surrounding them in a membrane with a soluble outer layer. TAG’s in epithelial cells of the small intestine are packaged into chylomicrons which enter the blood through the lymph system. Lipoprotein lipase allows for the movement of free fatty acids through the capillaries to muscle and adipose tissue.

Fatty acids are the preferred fuel for what tissues. (3)

Red muscle, which is built for endurance, uses fat as a fuel source since it is more stable, produces more energy when oxidised and is 2/3 water.

Describe how free fatty acids are transported in the aqueous environments of the blood and cytosol.

Adipose lipase cleaves TAGs into FFA’s and glycerol. FFA’s passively diffuse into the blood where it binds to albumin and enters cell tissues. FFA’s travel through a cell membrane and bind to a Fatty-acid-binding-protein.

Describe how fatty acids are activated for oxidation.

• As fatty acids enter the mitochondria they are activated by being attached to acyl-CoA to make fatty acyl-CoA

• Fatty acyl-CoA pass from the cyotsol to the intermembrane space via the fatty acyl-CoA carrier protein in the outer membrane.

• Fatty acyl-CoA is reacted with carnitine to form fatty-acyl-carnitine which allows it to pass through the fatty acyl-carnitine carrier protein in the inner membrane into the matrix.

• Carnitine acyl-transferase II reverses the carnitine bond, forming again fatty acyl-CoA

Write the overall reaction for the oxidation of a saturated fatty acid with an even number of carbons and identify in which of the products the energy released during the oxidation of fatty acids has been conserved/captured.

The first three reactions in β-oxidation are oxidation, then hydration, then oxidation again. Energy isn’t directly captured from β-oxidation, it is stored in the reducing agents. FAD is reduced to FADH2 in the first step and NAD+ is reduced to NADH, H⁺.

The fourth reaction is a cleavage of the alpha and beta carbons, releasing Acetyl-CoA. CoASH is added to to the remaining carbon chain and it enters the cycle again, two carbons shorter.

Describe the key reactions in the citric acid cycle and how energy is conserved/captured in the citric acid cycle.

There are two main parts to the CAC: Release of Carbon and Regeneration of the original molecule.

• The first key reaction is the condensation of Acetyl-CoA and oxaloacetate. This releases some energy, but the two carbons for Acetyl-CoA will need to be removed.

• Then the first carbon is removed via

Describe how the citric acid cycle may be inhibited and the consequences of inhibition on energy metabolism.

• 1080 (Sodium Fluoroacetate) inhibits the CAC by reacting with oxaloacetate via citrate synthase to form fluorocitrate instead of just citrate. The following two reactions make citrate ready for decarboxylation. Both steps are catalysed by aconitase. Fluorocitrate is converted into a substrate that binds tightly to aconitase and inactivates the enzyme.

• This inhibition causies buildup of Acetyl-CoA, decrease in reduced coenzymes, decrease ATP

Explain the sequential digestion of proteins.

To break up proteins, proteases/peptidases are used to hydrolyze the peptide bonds. Endopeptidases hydrolyse specific bonds inside the protein, specified by the adjacent side chains. Exopeptidases hydrolyse bonds near the ends of the protein, carboxypeptidases release amino acids, di or tri peptides from the carboxy terminal of the protein, and aminopeptidases do the same for the amino terminal. 

Explain what is meant by zymogens and what their purposes are in the context of protein breakdown.

Proteases are dangerous in the body, so they are synthesized in their inactive form called zymogens. When these zymogens enter the gastrointestinal tract, the low pH activates them and they are capable of activation other proease zymogens.

Briefly describe the absorption of amino acid and peptide absorption from the intestine.

Peptides of four amino acids or longer have very little absorption. Co-transporters with H⁺ ions move di- and tri-peptides