Biochemistry 3380G Lecture Notes - Lecture 11: Insulin Resistance, Gluconeogenesis, Blood Sugar

1. Integrated metabolism

A. A molecule of glucose that you eat can eventually be transformed into part of a fatty acid that you store. Circle the pathways/cycles below that are part of this overall flow of carbon atoms. Cross out any that are not.

Gluconeogenesis, beta-oxidation, citric acid cycle, glycolysis, urea cycle, fatty acid synthesis

B. Trace the metabolic path of this glucose molecule through the enzymes it encounters along the way to being made into fat. Write all the enzymes in the list below into the proper places in the figure below. If the enzyme is not used, write its name in a “not used" column. If it is used, write the enzyme in the order that the carbon atoms from glucose encounter the enzymes.

Pyruvate dehydrogenase, fumarase, aldolase, lactate dehydrogenase, pyruvate kinase, acetyl CoA carboxylase, fatty acid synthase, hexokinase, carnitine acyltransferase, ATP synthase

B. What is the minimum number of glucose molecules that would be necessary to be the carbon source for synthesis of a 16-carbon fatty acid through this pathway?

C. How many net glucose can be made from one molecule of a 16-carbon fatty acid?

2. Describe each cycle/transport system (compounds, compartments, tissues) and explain its purpose:

A. citrate transport system

B. Cori cycle

C. glucose/alanine cycle

3.

Explain the logic of these pathway regulations:

A. Phosphofructokinase, not hexokinase, is the main regulation site of glycolysis.

B. SuccinylCoA inhibits the entry of acetyl CoA into the citric acid cycle.

C. NADH inhibits pyruvate dehydrogenase.

D. Citrate inhibits the citric acid cycle and activates acetyl-CoA carboxylase.

E. Insulin leads to activation of glycogen synthase.

10- With respect to regulation of fatty acid metabolism chose the FALSE statement from those below?

a) ACC and FAS synthesis is stimulated by Insulin

b) ACC and FAS synthesis is stimulated by the well-fed state

c) Starvation leads to an increase in the synthesis of ACC and FAS.

d) Adipose tissue levels of lipoprotein lipase also are increased by insulin and decreased by starvation.

e) The long-term regulation of fat metabolism is achieved by alteration of the rate of enzyme synthesis and turn-over

14-With respect to the clinical significance of ketogenesis, which of the statements below are FALSE?

a) The Ketone bodies are relatively strong acids

b) The increase of ketone bodies in the blood lowers the pH of the blood.

c) The acidification of the blood by an increase of ketone bodies in the blood is dangerous because it impairs the ability of hemoglobin to bind oxygen

d) A severe increase of ketone bodies in the blood occurs in untreated insulin-dependent diabetes mellitus.

e) none of the above

15-With respect to ketogenesis, which statement below is FALSE?

a) Acetoacetate and b-hydroxybutyrate are major substrates for the biosynthesis of neonatal cerebral lipids.

b) In early stages of starvation, the heart and skeletal muscle consumes primarily ketone bodies to preserve glucose for use by the brain.

c) The fate of the products of fatty acid metabolism is determined by an individual's physiological status.

d) Ketogenesis takes place only in the liver.

e) all of the above

16- When the body is deficient in oxaloacetate

a) acetyl CoA from the b-oxdiation pathway cannot enter the citric acid cycle

b) oxaloacetate is diverted to gluconeogenesis

c) acetyl CoA is diverted to form the ketone bodies

d) all of the above are true

e) none of the above

17- The synthesis of ketone bodies involves

a) synthesis of acetoacetyl-CoA by reversal of the thiolase reaction of fatty oxidation

b) synthesis of b-hydroxy-b-methylglutaryl-CoA (HMG-CoA)

c) cleavage of HMG-CoA to acetoacetate.

d) b-Hydroxybutyrate is produced by reduction of acetoacetate.

e) all of the above

18- Which of the statements about ketone body production is FALSE?

a) Ketone bodies are produced when there is more acetyl-CoA in the liver than can be oxidized in the citric acid cycle.

b) Ketone bodies production is not a normal process, and occurs only in diabetes or starvation

c) The ketone bodies produced in the body are the free acids and not the CoA esters.

d) When fatty acid oxidation in the liver is uncontrolled, ketone body production becomes excessive and life-threatening because these acidic compounds lower the pH of blood

e) When fatty acid oxidation

19- In which of the following ways can the 4-carbon compound acetoacetyl CoA produced in fatty acid degradation be further metabolized?

a) It can break down further to form acetyl CoA,

b) It can be converted to the ketone bodies

c) It can be used for synthesis of cholesterol and its many deriv­atives.

d) It can do all of the above

e) It can do none of the above

20- Acetyl CoA from the beta-oxidation pathway cannot enter the citric acid cycle in which of these circumstances?

a) periods of fasting

b) periods of starvation

c) diabetes

d) when the body is deficient in oxaloacetate

e) all of the above