Download Regulation of carbohydrate metabolism

Regulation of carbohydrate
metabolism
Overview of the major
pathways of glucose
metabolism
Regulation of gluconeogenesis and
glycolysis:
 inactivation of the glycolytic enzymes and activation
of the enzymes of gluconeogenesis
1. Pyruvate ↔ PEP
Pyruvate kinase - inactivation by cAMP
(glucagon)
Phosphoenolpyruvate carboxykinase induced by glucagon, epinephrine, and
cortisol
2. Fructose 1,6-P ↔ Fructose 6-P
Phosphofructokinase - activated
by fructose 2,6-P
Fructose 1,6-bisphosphatase - inhibited
by fructose 2,6-P
3. Glucose 6-P ↔ Glucose
Glucokinase - high Km for glucose,
induced by insulin
Glucose 6-phosphatase - induced during
fasting
Metabolism of
glycogen
Regulation of glycogenolysis in the liver by
glucagon:
cAMP → protein kinase A:
1. inactivates glycogen synthase
2. activates glycogen phosphorylase
Regulation of glycogenolysis in muscle:
Regulation of liver and muscle glycogen metabolism:
State
Regulators
Response
Fasting
Glucagon ↑, Insulin ↓
cAMP ↑
Glycogen degradation ↑
Glycogen synthesis ↓
Carbohydrate meal
Glu ↑, Glucagon ↓, Insulin ↑
cAMP ↓
Glycogen degradation ↓
Glycogen synthesis ↑
Exercise and stress
Adrenalin ↑
cAMP ↑, Ca2+-calmodulin ↑
Glycogen degradation ↑
Glycogen synthesis ↓
Fasting (rest)
Insulin ↓
Glycogen synthesis ↓
Glucose transport ↓
Carbohydrate meal (rest)
Insulin ↑
Glycogen synthesis ↑
Glucose transport ↑
Exercise
Epinephrine ↑
AMP ↑, Ca2+-calmodulin ↑,
cAMP ↑
Glycogen synthesis ↓
Glycogen degradation ↑
Glycolysis ↑
Liver
Muscle
Glucose homeostasis:
 maintenance of blood glucose levels near 80 to 100 mg/dL (4,4-5,6 mmol/l)
 insulin and glucagon (regulate fuel mobilization and storage)
Hypoglycemia prevention:
1. release of glucose from the large glycogen stores in the liver (glycogenolysis)
2. synthesis of glucose from lactate, glycerol, and amino acids in liver (gluconeogenesis)
3. release of fatty acids from adipose tissue (lipolysis)
Hyperglycemia prevention:
1. conversion of glucose to glycogen (glycogen synthesis)
2. conversion of glucose to triacylglycerols in liver and adipose tissue (lipogenesis)
Major sites of insulin action on fuel
metabolism:
The storage of nutriens
•
glucose transport into muscle and
adipose tissue
•
glucose storage as glycogen
(liver, muscle)
•
conversion of glucose to TG
(liver) and their storage (adipose
tissue)
•
protein synthesis (liver, muscle)
•
inhibition of fuel mobilization
Major sites of glucagone action
on fuel metabolism:
Mobilization of energy stores
1. release of glucose from liver
glycogen
2. stimulating gluconeogenesis from
lactate, glycerol, and amino acids
(liver)
3. mobilizing fatty acids (adipose
tissue)
Repetition:
1. 3 key enzymes for the regulation of glycolysis (their activation). The
role of Fructose 2,6-P in the regulation of glycolysis and
gluconeogenesis.
2. 3 key sites for the regulation of gluconeogenesis (their activation).
3. The signal pathway for the activation of glycogen degradation by
glucagon.
4. Main regulators of glycogen degradation in liver and muscle.
5. Pathways preventing hypoglycemia and hyperglycemia.
The highest-energy phosphate
bond in ATP is located between
which of the following groups?
• Adenosine and phosphate
• Ribose and phosphate
• Two hydroxyl groups in the ribose
ring
• Two phosphate groups
ATP
AMP
ADP
Which of the following statements
correctly describes reduction of one of
the electron carriers, NAD+ or FAD?
• NAD+ accepts two electrons as hydrogen
atoms to form NADH2.
• NAD+ accepts two electrons that are each
donated from a separate atom of the
substrate.
• NAD+ accepts two electrons as a hydride
ion to form NADH.
• FAD releases a proton as it accepts two
electrons.
• FAD must accept two electrons at a time.
+H-H-
A patient has just suffered a
heart attack. As a
consequence, his heart would
display which of the following
changes?
• An increased intracellular O2
concentration
• An increased intracellular ATP
concentration
• An increased intracellular H+
concentration
• A decreased intracellular Ca2+
A patient diagnosed with thiamine
deficiency exhibited fatigue and muscle
cramps. The muscle cramps have been
related to an accumulation of metabolic
acids. Which of the following metabolic
acids is most likely to accumulate in a
thiamine deficiency?
• Isocitric acid
• Pyruvic acid
• Succinic acid
• Malic acid
• Oxaloacetic acid
TPP
TPP
During exercise, stimulation of the
tricarboxylic acid cycle results
principally from which of the
following?
• Allosteric activation of isocitrate
dehydrogenase by increased NADH
• Allosteric activation of fumarase by
increased ADP
• A rapid decrease in the concentration
of four carbon intermediates
• Stimulation of the flux through a
number of enzymes by a decreased
NADH/NAD+ ratio
Coenzyme A is synthesized
from which of the following
vitamins?
•
•
•
•
•
Niacin
Riboflavin
Vitamin A
Pantothenate
Vitamin C
A 25-year-old female presents with chronic fatigue.
Results of a series of blood tests suggest that her red
blood cell count is low because of iron deficiency anemia.
Such a deficiency would lead to fatigue because of which
of the following?
•
•
•
•
•
Her decrease in Fe-S centers is impairing the transfer of
electrons in the electron transport chain.
She is not producing as much H2O in the electron transport
chain, leading to dehydration, which has resulted in fatigue.
Iron forms a chelate with NADH and FAD(2H) that is necessary
for them to donate their electrons to the electron transport chain.
Iron acts as a cofactor for α-ketoglutarate DH in the TCA cycle, a
reaction required for the flow of electrons through the electron
transport chain.
Iron accompanies the protons that are pumped from the
mitochondrial matrix to the cytosolic side of the inner
mitochondrial membrane. Without iron, the proton gradient
cannot be maintained to produce adequate ATP.
Which of the following would be
expected for a patient with an
OXPHOS disease?
• A high ATP:ADP ratio in the mitochondria
• A high NADH:NAD+ ratio in the mitochondria
• A deletion on the X chromosome
• A high activity of complex II of the electron
transport chain
• A defect in the integrity of the inner mitochondrial
membrane
Dinitrophenol acts as an uncoupler
of oxidative phosphorylation by
which of the following
mechanisms?
• Activating the H+-ATPase
• Activating coenzyme Q
• Blocking proton transport across the inner
mitochondrial membrane
• Allowing for proton exchange across the
inner mitochondrial membrane
• Enhancing oxygen transport across the
inner mitochondrial membrane
Consider the following experiment. Carefully
isolated liver mitochondria are incubated in the
presence of a limiting amount of malate. Three
minutes after adding the substrate, cyanide is
added, and the reaction is allowed to proceed
for another 7 minutes. At this point, which of the
following components of the electron transfer
chain will be in an oxidized state?
•
•
•
•
•
Complex I
Complex II
Complex III
Coenzyme Q
Cytochrome C
Limit