Amyloid precursor protein (APP) is an integral membrane protein with important functions at synapses between nerve cells. It is cleaved within the membrane to release an extracellular peptide fragment called Ab. When Ab peptides accumulate, they can aggregate to form amyloid fibrils associated with Alzheimer’s disease

The cleavage of APP to Ab is catalyzed by Presenilin-1. Presenilin-1 is inhibited by transition state analogues specific for aspartyl proteases.

A. In one sentence, describe why transition state analogues are excellent competitive inhibitors of enzymatic activity.

B. Presenilin-1 has two important catalytic residues, Asp257 and Asp385, which cleave APP to Ab within the hydrophobic membrane. Describe TWO reasons why these catalytic aspartates have elevated pKa values.

C. During catalysis, there is a buildup of negative charge on the oxygen atom of the scissile amide bond. To stabilize the transition state, Asp385 donates a proton to the oxyanion that forms. To what amino acid would you mutate Asp385 to prevent proton transfer whilst having minimal impact on the rest of the protein? Will this amino acid still be able to stabilize the transition state via hydrogen bonding?

D. Aspartyl proteases directly activate water for hydrolysis without forming a covalent enzyme-substrate intermediate. Draw a mechanism for peptide hydrolysis. Clearly show Asp385 stabilizing the oxyanion transition state. Clearly show what role Asp257 may have.

Which of the following scenarios is an example of additivity?

In the muscle, when are glycolysis and the citric acid cycle both active and when are they both turned off?(2 points) When is only glycolysis active and when is only the citric acid cycle active?(2 points) Why? (2 points)

Which of the following statements about hemoglobin is false?

Which of the following statements about oxygen delivery to the body tissues is false?

Digestion is necessary because…

Which of the following is not a type of biomolecule that must be digested before it can be absorbed?

Which of the following is not a function of human blood?

Which of the following statements about human blood is false?

Which enzyme unwinds?

Which enzyme prevents supercoiling?

Which enzyme lays down RNA?

Which enzyme replaces the primer?

Which enzyme connects Okazaki fragments?

Your firm is considering leasing a $ 51000 copier. The copier has an estimated economic life of eight years. Suppose the appropriate discount rate is 9.1 % APR with monthly compounding. Classify each lease below as a capital lease or operating lease, and explain why:

a. A four-year fair market value lease with payments of $ 1145 per month.

b. A six-year fair market value lease with payments of $ 800 per month.

c. A five-year fair market value lease with payments of $ 920 per month.

d. A five-year fair market value lease with payments of $ 1010 per month and an option to cancel after three years with a$ 9400 cancellation penalty.

As illustrated in your text, identify two ways that Raphael's Madonna of the Meadow is similar to da Vinci's Madonna of the Rocks in style and/or composition, and two ways that it is different.

please answer all or explain.

11. Circle the statement that is not true for hemoglobin.

A.The R-state has a high affinity for diatomic oxygen.

B. 2,3-bisphosphoglycerate stabilizes the T-state.

C. Carbon monoxide stabilizes the R-state.

D. H⁺ ions stabilize the R-state.

12. Circle the statement that is not true for CO₂.

A. It is a non-polar molecule that can diffuse across cell membranes.

B. It can combine with terminal amines on proteins to form carbamates.

C. It is primarily transported in the blood as HCO₃.

D. It inhibits the release of O₂ from hemoglobin.

13. What environmental pressure is considered responsible for keeping the sickle cell gene in the human gene pool?

14. Circle the statement that is not true for an enzyme.

A. It reduces ΔG for a reaction.

B. It stabilizes the transition state in a reaction.

C. It increases the reaction rate in both the forward and reverse directions.

D. It has a catalytic site that is a crevice or cleft in the molecule.

15. What are the two types of cofactors that interact with enzyme? (8 points)

In Mediterranean countries, it is traditionally recommended to drink a glass of olive oil per day to stay healthy. Consider that olive oil is made of 100% of triglycerides. Among the fatty acids contained in these triglycerides, 70% are oleic acid (monounsaturated fatty acid with 18 carbons), 10% are linoleic acid (polyunsaturated fatty acid (2 unsaturations) with 18 carbons) and linolenic acid (polyunsaturated fatty acid (3 unsaturations) with 18 carbons), 10% are palmitic acid (saturated fatty acid with 16 carbons), and 10% are stearic acid (saturated fatty acid with 18 carbons).

B. Explain how these triglycerides are digested in the intestine.

C.Explain how these lipids are distributed to peripheral tissues (explain in detail how these lipids are transported from the intestine to the peripheral tissues (or extra-hepatic tissues) : how they are transported in the bloodstream and how they are distributed to the peripheral tissues)

D. Explain the different fates of these fatty acids in the post-prandial period in the following organs: a) skeletal muscles, b) adipose tissue and c) the brain. For each metabolic pathway involved, name the pathway, give the initial substrate(s) and the final product(s) and the ultimate goal of each pathway (please do not describe the whole pathway!). Then, describe the limiting step(s) of each pathway: give the substrate and the product of each limiting reaction and the name of the enzyme that catalyzes each limiting reaction. Finally, briefly explain how these pathways are regulated during the post-prandial period. (13.5 marks)