BCHM 403 Lecture Notes - Lecture 3: Phosphorylase Kinase, Electrochemical Gradient, Ester

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plumgerbil611

15 Sep 2016

School

Binghamton University

Department

Biochemistry

Course

BCHM 403

Professor

Musselman

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Document Summary

#2: rxn is glucose + atp to give glucose-6-phosphate + adp. Note the lower value for h than for g. when [s] is at normal blood glucose level, h will be working close to vmax while g isn"t even working at half vmax. So the liver is allowing other cells to take up the glucose. This also happens when blood glucose level is lower or higher than normal. What is important is that the liver always allows other cells to take up the glucose preferentially: there are at least 2 conformations for a: more active r and less active t forms. At very high [s], the vi of a will be at vmax whether inhibitor or activator is present. With b, even at very high [s], the binding of inhibitor will still lower activity while binding of activator will raise activity since it is vmax that changes: glycogen phosphorylase catalyzes the breakdown of glycogen reserves by phosphorolysis.

Related Questions

i need question number nine please

Case Study Section 2 â glycolysis
Based on âMonday at the Metabolic Clinic, Adventures in Glycolysisâ by Nancy Boury (National Center for Case Study Teaching in Science)

Background:
You have been chosen for a very competitive undergraduate clinical internship at St. Visintainerâs Hospital and Metabolic Clinic working with Dr. Saccharo, an expert in enzyme deficiency disorders related to glycolysis. Before your first day Dr. Saccharo has asked that you review the reactions of glycolysis and the concept of isoenzymes.

Recall that isoenzymes are groups of enzymes that catalyze the same reaction in that they use the same reactants to product the same products. They may have different genes, tissue expression, developmental timing of expression, and affinities for their substrates. As an example, phosphofructokinase-1 has 3 isoenzyme forms: PFK-L is expressed in the liver and the gene is found on chromosome 21; PFK-M is expressed in the muscle and the gene is found on chromosome 12; and PFK-P is expressed in platelets and the gene is found on chromosome 10.

Question 1:
If a person would be deficient in all 3 forms of PFK-1, this person would .
A. Have lower than normal glycogen stores.
B. Have more mitochondrial activity than normal.
C. Be dead.
D. Produce more energy per glucose molecule because glycolysis would be unregulated.

It is now Monday morning and you are ready to start seeing patients with Dr. Saccharo.

Patient 1:
Ann is a teenager and avid golfer who was referred to the clinic after being refused at the blood drive and tiring easily on the high school golf course during practice. Ann is examined and a blood sample was obtained for analysis of a glycolysis related metabolic panel. The results of her panel is below (levels: + = normal, - = decreased; ++= increased):
Blood Metabolic Panel
Blood Glucose +
Glucose-6-phosphate ++
Fructose-6-phosphate ++
Fructose-1,6,bisphosphate ++
Glyceraldehyde-3-phosphate ++
1,3-bisphosphoglycerate ++
Phosphoenolpyruvate ++
Pyruvate -
ATP -
Red Blood Cell Concentration -
Question 2:
Assuming that Dr. Saccharo is correctly assuming that Ann has a defect in glycolysis, what glycolytic enzyme is the most likely to have the defect based on the blood metabolic profile?
A. Hexokinase
B. Phosphofructokinase
C. Triose Phosphate Isomerase
D. Pyruvate Kinase
E. Aldolase

Patient 2:
Marie is a 32-year-old mother of three complaining of fatigue and muscle cramps with exercise. She had always blamed her intolerance to exercise on her sedentary lifestyle. However, she recently joined a gym and after a week of aerobics classes went to her physician, who ordered a series of blood tests. The blood work came back with abnormal results, leading to her muscle biopsy and referral to the metabolic clinic. Marieâs blood was subjected to the same metabolic panel used before with the following results:
Blood Metabolic Panel
Blood Glucose +
Glucose-6-phosphate ++
Fructose-6-phosphate ++
Fructose-1,6,bisphosphate -
Glyceraldehyde-3-phosphate -
1,3-bisphosphoglycerate -
Pyruvate -
ATP -
Red Blood Cell Concentration -

Marieâs muscle biopsy was also analyzed and showed an excess of glycogen.

Question 3:
What is the most likely enzyme deficiency for Marie?
A. Hexokinase
B. Phosphofructokinase
C. Triose Phosphate Isomerase
D. Pyruvate Kinase
E. Aldolase

Question 4:
If you wanted to test the ability of red blood cells to complete glycolysis what compound would you try to detect?
A. Fructose-6-phosphate
B. Aldolase
C. Pyruvate
D. Phosphofructokinase
E. Dihydroxyacetone phosphate

Question 5:
If you used a sample of Marieâs blood for this, what compound could you add to enable these cells to complete glycolysis?
A. Glucose
B. Fructose-1,6-bisphosphate
C. Insulin
D. Glucagon
E. Fructose-6-phosphate

Patient 3:
Leo is a 25-year-old accountant that is not anemic, has perfect teeth, but has experienced two fainting spells recently. One happened after accidentally drinking a non-diet soda; the other after eating ânaturally sweetenedâ fruit salad. His dentist referred him to Dr. Saccharoâs clinic. Dr. Saccharo suspects Leo may have Hereditary Fructose Intolerance (HFI) and has recommended a closely monitored fructose tolerance test.

Hereditary Fructose Intolerance is a recessive disorder where individuals lack a functional copy of one isoform of the enzyme aldolase, specifically Aldolase B (also known as fructose-1-phosphate aldolase). In the liver, fructose is phosphorylated by Fructokinase to fructose-1-phosphate, then is cleaved by Aldolase B to glyceraldehyde and dihydroxyacetone phosphate. Fructose-1-phosphate is also a known allosteric inhibitor of Glycogen Phosphorylase, the primary enzyme responsible for releasing glucose from glycogen.

Question 6:
As compared to a normal individual that consumes fructose, a person with HFI who ingested fructose would have (select all that apply):
A. High levels of blood fructose
B. High levels of blood fructose-1-phosphate
C. High levels of blood glucose
D. Low levels of blood fructose
E. Low levels of blood glucose

That afternoon Leo undergoes the fructose tolerance test with the following results:

Question 7:
Based on the results of the test, what was the effect of giving Leo the intravenous fructose?
A. A rise in blood glucose levels
B. A decrease in blood glucose levels
C. An increase in glycogen stores
D. A rapid drop in blood pressure

However there were complications: Soon after the test Leo orders and drinks a cup of tea, but after half the cup Leo passes out. Dr. Saccharo orders two sequential blood glucose checks. The first was 50 mg/dl and 15 minutes later Leoâs blood glucose was down to 40 mg/dl. With those results Dr. Saccharo injected something into Leoâs IV and within minutes Leo was back to normal.

Question 8:
From these results does it appear that Leo has HFI?
A. Yes
B. No
C. It is unclear from the results

Question 9:
What did Dr. Saccharo inject into Leoâs IV line?
A. Insulin
B. Glucagon
C. Glucose
D. Fructose
E. Phosphofructokinase

Dr. Saccharo puts Leo on a restricted diet and orders follow-up visits.

Question 10:
Which of the following foods/ingredients would Leo NOT be allowed to eat?
A. Artificial sweeteners
B. High starch foods, such as potatoes
C. Sweet tea made with cane sugar
D. Any dairy products

Dr. Saccharo puts Leo on a restricted diet and orders follow-up visits.

Case Study Section 2 â glycolysis
Based on âMonday at the Metabolic Clinic, Adventures in Glycolysisâ by Nancy Boury (National Center for Case Study Teaching in Science)

Question 9:
What did Dr. Saccharo inject into Leoâs IV line?
A. Insulin
B. Glucagon
C. Glucose
D. Fructose
E. Phosphofructokinase

indigolocust876

Based on âMorgan: A case of Diabetesâ by Lisa Rubin and Clyde Freeman Herreid (National Center for Case Study Teaching in Science)

The Patient:

Morgan Water is a 27-year old Native American that lives on a reservation in Oklahoma. Nearly Â¼ of Morganâs tribe has diabetes but she has no direct family history of diabetes, heart disease, or other serious conditions. She is however obese (BMI = 32) and leads a sedentary lifestyle. Morgan has been suffering from an increasing persistence of symptoms including unusual thirst, dizziness, blurred vision, and numbness in her right foot. The symptoms have been developing over several months but as she is planning her wedding she attributed them to nerves. She is finally persuaded to see her family doctor. Her non-fasting blood glucose level was elevated so the doctor has her return the next morning for a fasting blood sample so they could more accurately measure her blood glucose and insulin. Her blood results are below:

Test	Morganâs values	Normal range	Pre-Diabetic range	Diabetic range
Plasma glucose, mg/dl	260	70 -139	140 - 199	â¥ 200
Fasting glucose, mg/dl	140	â¤ 99	100 - 125	â¥ 126
A1C, %	7.6	~ 5	5.7 â 6.4	â¥ 6.5
Fasting Insulin, mIU/ml	34	2 - 10	10 - 20	â¥ 20

Question 1:

Based on her history and blood results, what do you think is the most likely diagnosis for Morgan?

A. Type I Diabetes Mellitus

B. Type II Diabetes Mellitus

C. Pre-Diabetes

D. Cardiovascular Disease

Question 2:

What is the cause of Morganâs disease?

A. It is an auto-immune disorder that destroys the Î²-cells of her pancreas so she produces less

insulin than normal.

B. She has a genetic mutation that results in less insulin receptor being produced than normal.

C. She has developed insulin resistance, where her insulin receptors do not recognize the insulin her

body produces, likely due to her obesity.

D. There is no known cause, it can happen spontaneously.

Morgan is worried that she will have to spend the rest of her life giving herself injections but her doctor does not prescribe insulin injections.

Question 3:

Why would injections of insulin not help Morgan if she has hyperglycemia?

A. Her body is already producing excess insulin but not responding to it.

B. Her problem is with her insulin receptors responding to insulin.

C. Excess insulin will only exacerbate her insulin resistance.

D. All of the above.

Question 4:

Given Morganâs metabolic state, which of the following pathways would you expect to be active in Morganâs cells (select all that apply)?

A. Glycolysis

B. Gluconeogenesis

C. Î²-oxidation

D. Amino acid degradation

E. Protein synthesis

Based on âMorgan: A case of Diabetesâ by Lisa Rubin and Clyde Freeman Herreid (National Center for Case Study Teaching in Science)

The Patient:

Test	Morganâs values	Normal range	Pre-Diabetic range	Diabetic range
Plasma glucose, mg/dl	260	70 -139	140 - 199	â¥ 200
Fasting glucose, mg/dl	140	â¤ 99	100 - 125	â¥ 126
A1C, %	7.6	~ 5	5.7 â 6.4	â¥ 6.5
Fasting Insulin, mIU/ml	34	2 - 10	10 - 20	â¥ 20

The recommendation of Morganâs doctor was to improve her exercise, good nutrition, and weight loss. He recommends meeting with a nutritionist to assist Morgan in her weight loss goals. When Morgan got home and told her family the diagnosis they however had LOTS of suggestions on how she can lose weight. Below is a description of the advice given to her by three family members.

Best friend Savannah:

âYou know how Iâve been losing weight? Well, Iâve been on the Atkinsâ Diet. I heard about it on TV. Itâs great! You get to eat steak, chicken wings, and all the good stuff. All you have to do is limit carbohydrate intake. You should definitely give it a try. This diet has been around for years and it has worked for lots of people, including me.â

*Note: Atkinâs Diet recommends: 10% carbohydrates, 55% fats, 35% protein

Brother Alan:

âI think the best thing for you to do is exercise and stop eating all of that pizza and candy and food filled with fat. Our people never used to eat that junk. I say eat meals that are nutritionally balanced and high in fiber and low in refined sugars and saturated fats. And run a lot. Stop sitting around the house.â

Grandfather:

âMorgan, it is true that it is best to live in harmony and balance â to eat a nutritionally balanced diet that includes carbohydrates, proteins, and âgoodâ fats to meet your bodyâs needs. That is good. But look to your heritage. Our people were never overweight before we started eating âcivilizedâ food. Look to our native diet. I think you should look to traditional herbal remedies for help. What Alan says is true. Exercise is good. But it is sometimes not enough. Our people have always looked to natural medicine for cures. They will lift your spirits and energize you. Then you will lose weight and you will be healthy again. I hear the herbs from the diet shop are safe and good. But you must take them like the medicine label says. It canât hurt to try them.â

*Note: these herbal supplements Morganâs grandfather is recommending contain the herb

ephedra (ephedrine).

Question 5:

Given Morganâs metabolic state, what is the primary fuel source for her cells currently?

A. Carbohydrates (glucose)

B. Fats

C. Proteins

D. It is a balance of all three

Question 6:

Metabolic ketoacidosis is a common problem with diabetics, which is caused by which of the following?

A. Excessive oxidation of fatty acids, leading to an accumulation of ketone bodies in the blood.

B. Excessive oxidation of glucose, leading to an accumulation of ketone bodies in the blood.

C. Excessive oxidation of proteins, leading to an accumulation of ammonia in the blood.

D. Hyperglycemia.

Question 7:

Which weight loss suggestion is designed to achieve some level of ketosis?

A. Atkins Diet

B. Exercise

C. High fiber diet

D. Herbal treatments

Question 8:

One major side effect of the herbal supplement can be hot flashes and increased perspiration due to increased thermogenesis, what is the likely cause of the heat production?

A. Increasing the activity of phosphfructokinase-1.

B. Increasing the activity of the pyruvate dehydrogenase complex.

C. Increasing the activity of citrate synthase.

D. Increasing the activity of uncoupling proteins.

Question 9:

Would substituting fiber and complex carbohydrates (larger % cellulose) for the simple sugars and starches (high sucrose and amylose/amylopectin) help Morgan lose weight, why?

A. Yes, because complex carbohydrates like cellulose are largely indigestible so they pass through

the digestive tract without being absorbed.

B. Yes, cellulose contains less glucose residues than amylose or amylopectin.

C. Yes, because the fructose in sucrose is much more responsible for weight gain than the glucose.

D. No, because cellulose, amylose, and amylopectin are all composed of glucose so it doesnât

matter.

Question 10:

Which weight loss suggestion will lead to an increased need for gluconeogenesis?

A. Atkins Diet

B. Exercise

C. High fiber diet

D. Herbal treatments

BCHM 403 Lecture Notes - Lecture 3: Phosphorylase Kinase, Electrochemical Gradient, Ester

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