3. Glucose and Carbohydrate Metabolism (Part II) Flashcards
1
Q
Which enzyme allows the conversion of glycogen to glucose?
A
Glucose-6-phosphatase
2
Q
Where is glucose-6-phosphatase present?
A
Solely in the liver, kidney, and gut
3
Q
Why can’t muscle glycogen export glucose?
A
- Because muscle does not possess glucose-6-phosphatase
- Glucose is the only substance within the pathway that may cross the plasma membrane
4
Q
Which cells may synthesize glucose from gluconeogenic precursors?
A
Hepatocytes (liver)
5
Q
Describe the Cori Cycle.
A
- Glycogen is converted to lactate in muscle tissue.
- Lactate is transported to the liver.
- Lactate is converted to glucose.
- Glucose is transported to muscle.
6
Q
Describe the Glucose-Alanine Cycle.
A
- Pyruvate in peripheral cells accepts an amino group, synthesizing alanine.
- Alanine travels to the liver, where it becomes pyruvate.
- Pyruvate becomes glucose through gluconeogenesis.
- Glucose is transported to peripheral tissues.
7
Q
What is the brain’s requirement for glucose per day?
A
120 grams (480 kilocalories)
8
Q
How much glucose does hepatic glycogen availability store per day?
A
190 grams
9
Q
How much water does the liver store?
A
- 4 grams of water for every gram of glycogen (190 grams per day)
- Kilogram of both water and glycogen
10
Q
What explains rapid weight loss during a fasting state (or a very low-calorie diet)?
A
- Glycogen stores are broken down to maintain the brain’s glucose requirement
- Promotes a rapid loss of water through the loss of glycogen
11
Q
Why would some people call gluconeogenesis, glucopaleogenesis?
A
Because the glucose that we’re synthesizing during gluconeogenesis is not new, as we are regenerating glucose from precursors
12
Q
What are gluconeogenic precursors?
A
Amino acids, pyruvate, and glycerol
13
Q
How does glycerol relate to glucose?
A
- Three-carbon unit from TG
- Originally synthesized from glucose
14
Q
How does pyruvate relate to glucose?
A
- Product of glycolysis
- Generated from glucose
15
Q
How do amino acids relate to glucose?
A
The carbon skeleton is synthesized from glucose
16
Q
Where does gluconeogenesis occur? What is it stimulated by?
A
- In the liver
- Stimulated by glucagon and gluocorticoids when plasma glucose is low
17
Q
Why would stress hormones encourage gluconeogenesis? Give examples of these hormones.
A
- To increase the availability of glucose in order to respond to the crisis at hand (fight-or-flight)
- Cortisol, epinephrine
18
Q
What occurs to muscle during a fast?
A
- Gluconeogenesis breaks down protein to allow for the utilization of glucogenic amino acid precursors
- While protein catabolism is not ideal, survival instincts prevail over muscle mass
19
Q
How long does it take for glycogen stores to become exhausted?
A
Around 24 hours
20
Q
How is glucose homeostasis maintained at first during a fast?
A
- Glycogenolysis
- Gluconeogenesis
21
Q
What does the oxidation of fatty acids create? When does this occur?
A
- During a long-term fast
- Creates Acetyl-CoA
22
Q
What occurs to Acetyl-CoA when there is no oxidation of glucose?
A
- Acetyl-CoA accumulates
- Joins together to form ketone bodies
23
Q
What are the three ketone bodies?
A
- Acetoacetate
- Acetone
- 3-hydroxybutyrate
24
Q
What is the function of ketone bodies?
A
- May be transported in circulation and utilized in the brain for energy purposes
- Good survival mechanism if fasting, as it provides a protein-sparing effect, while feeding the brain with energy
25
Why does Acetyl-CoA accumulate when there is no glucose oxidation?
- Anaplerosis is required to regenerate TCA cycle intermediates
- If there is no glucose, the precursors from glycolysis (pyruvate) may not be utilized for anaplerosis
- Acetyl-CoA is produced faster than it is removed in the TCA cycle
- Also, fatty acid B-oxidation occurs in the absence of glucose, which causes Acetyl-CoA to accumulate
26
What occurs when ketone bodies are overproduced?
- Cause metabolic ketoacidosis
- Decreases pH of the blood
- Impacts the brain
- Potentially fatal
27
What is the life-threatening problem of untreated diabetes?
Ketoacidosis
28
What occurs first during a long-term fast: protein breakdown or fat breakdown?
Protein breakdown, then fat breakdown (producing ketone bodies)
29
How is substrate utilization measured?
- CO2 that we are producing and the O2 that we consume in relation to normal room air
- Indirect calorimetry
30
What is the equation for the respiratory quotient?
RQ = CO2 produced/O2 consumed
31
What is the RQ if an individual is solely burning carbohydrates?
1.0
32
What is the RQ if an individual is solely burning fat?
0.7
33
Why is the RQ lower if an individual is burning fat?
- Fatty acid molecule has more carbons than oxygens
| - More oxygen must be consumed from room air than glucose
34
What is the basal metabolic rate for a 70kg man?
- 1.0 kcal/kg/h
| - 1700 kcal/day
35
What is the basal metabolic rate for a 55kg man?
- 0.9 kcal/kg/h
| - 1200 kcal/day
36
Why is the basal metabolic rate lower in women than in men?
Because women possess less muscle mass
37
What percentage does the basal metabolic rate make up in total energy expenditure?
67%
38
What percentage does diet-induced thermogenesis make up in total energy expenditure?
10%
39
What is diet-induced thermogenesis?
The amount of energy expenditure above the resting metabolic rate due to the cost of processing food for use and storage
40
What is adaptive thermogenesis?
Energy needed to warm the body in a cool environment, and cool the body in a warm environment
41
What percentage does activity make up in total energy expenditure?
23% (highly variable)
42
Which component of energy expenditure may be modulated?
Activity
43
Where is GLUT1 present?
- RBCs
- Brain-blood barrier
- Fetus
44
Why is GLUT1 important?
- Because RBCs have no organelles (no TCA cycle) to produce energy
- Their only source of ATP is glycolysis, so they need glucose
45
Where is GLUT2 present?
- Liver
- B-cells of pancreas
- Kidney
- Small intestine
46
Where is GLUT3 present?
- Brain (neurons)
| - Placenta
47
Where is GLUT4 present?
- Muscle
- Heart
- Adipose tissue
48
Where is GLUT5 present?
Small intestine
49
Which GLUT transporter functions increase at low glucose concentrations?
GLUT1
50
Which GLUT transporter has high affinity at LOW concentrations?
GLUT3
51
Which GLUT transporter has high capacity and low affinity?
GLUT2
52
Which GLUT transporter is insulin-mediated?
GLUT4
53
Which GLUT transporter is the fructose transporter?
GLUT5
54
The effect of GLUT4 is immediate, what does that suggest?
That the GLUT4 transporter protein is not synthesized, but stored
55
How does insulin receptor signalling increase glucose entry?
Stimulates GLUT4 exocytosis and incorporation into the cell membrane
56
Which cells cannot synthesize glucose from gluconeogenic precursors?
Peripheral cells
57
What must glucose that is metabolized in peripheral cells be converted to in order to allow for gluconeogenesis to occur in the liver? What cycle is this?
- Lactate
| - Cori cycle
58
How much ATP does the Cori Cycle require?
- 4 ATP
| - It is energetically expensive
59
What are amino groups synthesized to in the liver through the Glucose-Alanine Cycle?
Urea
60
What energy sources does an individual rely on during a sprint?
- Creatine-phosphate
- Myoglobin
- Glycolysis
61
What energy sources does an individual rely on during a marathon?
Glycogen stores supply energy for 1 to 3 hours
62
How is the quantity of glycogen stores maximized for marathon running?
By carbohydrate loading (low glycemic index, high carbohydrate diet)
63
Which amino acids is creatine phosphate derived from?
Glycine and arginine
64
How does creatine phosphate provide energy?
The phosphate bonds store energy (high-energy bond)
65
Where is myoglobin found? What is its function?
- Found in muscle tissue
| - Provides an oxygen store
66
How does glycolysis provide energy when there is low oxygen?
Provides a small amount of energy, and produces lactate
67
What are the effects of hypoglycemia?
- May cause hypoglycemic coma
| - Ex: insulin shock when an individual with diabetes consumes too much insulin
68
What are the four major effects of hyperglycemia?
- Dehydration
- Glucosuria
- Ketoacidosis
- Cerebral edema (diabetic coma)
69
How does the pancreas function as an exocrine gland?
Produces digestive enzymes, which are secreted to the small intestine through the pancreatic duct
70
How does the pancreas function as an endocrine gland?
Produces hormones (insulin and glucagon), which are released in the blood stream
71
Where are insulin- and glucagon-producing cells found? What kind of cells are they?
- Islets of Langerhans
- Insulin: B-cells
- Glucagon: a-cells
72
How is insulin synthesized?
- Preproinsulin (single polypeptide chain)
- Proinsulin (signal sequence is removed, and contains three disulfide bonds)
- Mature insulin, composed of 2 polypeptide chains (removal of C-peptide)
73
How many polypeptide chains is insulin composed of? How are they linked? Are they synthesized in multiple units?
- 2 chains (or more)
- Linked by disulfide bonds
- Synthesized in a SINGLE unit
74
Insulin is a metalloprotein. Which ions does it contain?
Zinc
75
High blood glucose causes an increase of glucose entry within pancreatic cells through _______.
GLUT2
76
Increased ATP production due to the entry of glucose in pancreatic cells causes what?
- A potassium channel closes
| - Depolarization of the cell
77
What is the effect of depolarizing the pancreatic cell?
Opening of voltage-gated calcium channels
78
What does calcium activate within the pancreatic cell?
- Activates insulin gene expression via CREB (Calcium Responsive Element Binding Protein)
- Calcium is also stored in vesicles to allow for fast response
- Calcium allows for the exocytosis of insulin
79
Which processes do the signalling proteins of the insulin receptor function to increase?
- Glycogen synthesis
- Fat synthesis
- Protein synthesis
- Growth and gene expression
- Amino acid influx
- Glucose influx
80
What is the cause of T1DM? What percentage of diabetics possess T1DM?
- Cell-mediated autoimmune B-cell destruction, which causes a tremendous decrease in insulin production
- Genetic predisposition
- 5-10% of all cases of diabetes
81
Which scientists discovered the protein insulin?
- Charles Best
- Rederick Banting
- University of TOronto
82
What is the peak age of onset of T1DM? What weight do individuals with T1DM have?
- During puberty
| - Normal or underweight
83
What is urinalysis?
Measures glucose and ketone concentration in urine
84
What is fasting plasma glucose concentration? What is the normal quantity and the diabetic quantity?
- Diabetics: over 7.0 mM/L
| - Normal: 5 mM/L
85
What is oral glucose tolerance? What is the diabetic quantity?
Diabetics: over 11 mM/L
86
What is the normal and diabetic range of glycated hemoglobin?
- Normal: 3.5 to 5.5%
| - Diabetics: over 6.5%
87
Which test measures long-term glucose control? Why?
- Glycated hemoglobin
| - Because hemoglobin is a long-lived protein
88
Apart from genetic predisposition, what could also cause T1DM?
Viral infection
89
In T1DM, serum lab tests for antibodies to what?
- Antibodies to glutamic acid decarboxylase (GAD), a protein found in pancreatic cells
- If the pancreatic cells are damaged, GAD would be found in the serum
90
What is the treatment for T1DM?
- Balance insulin shots (short- or long-acting) with their activity and food intake
- Islet cell transplantation
91
Which glycated hemoglobin value is measured to determine blood glucose concentrations?
Hemoglobin A1c
92
What is the hemoglobin A1c value in a healthy individual? What about in diabetics?
- Normal: 6%
| - Diabetics: 8% and above
93
What is the dichotomy in diabetes?
- Excess of blood glucose in the circulatory system
| - Deficit of blood glucose in many cells
94
T1DM results in a hyper_______ and hyper______ state.
hyperosmolar, hyperdiabetic
95
What is the long-term impact of T1DM on protein metabolism?
- There is an inappropriately high breakdown of protein and amino acid oxidation
- Translates into an increased requirement of protein
96
What is ketoacidosis manifested by?
- Ketones in the breath (acetone breath)
- Ketones in the blood (ketonemia)
- Ketones in the urine (ketonuria)
97
Which ketone may be detected in the breath?
Acetone
98
What transporters are present in the tubules of the kidney to absorb glucose from the lumen of the kidney to the blood?
- SGLT2 (lumen to cell)
| - GLUT2 (cell to blood)
99
What is glucose spilling into the urine directly related to?
- Concentration of glucose, and NOT insulin malfunctioning
| - There is a maximal rate at which SGLT2 can transport glucose
100
What is the maximal concentration at which SGLT2 can transport glucose in kidney tubules?
10 mM/L
101
What are the effects of an inhibitor of SGLT2? What are the side effects?
- More glucose lost in urine, which would lower blood glucose levels
- Increased urination (glucose pulls more water)
- Severe dehydration and excessive thirst
- General yeast infections
102
What are the acute issues of untreated diabetes?
- Hyperglycemia
| - Ketoacidosis
103
What are the chronic issues of untreated diabetes?
Angiopathy (pathology of blood vessels)
104
Which three microvascular issues arise with untreated diabetes?
- Retinopathy (eyes)
- Nephropathy (kidney)
- Neuropathy (nerve)
- Due to exposure to chronically high blood glucose
105
What occurs in nephropathy due to untreated diabetes?
- Exposure to chronically high blood glucose leads to the thickening of the glomerulus
- The nephron becomes leaking, allowing larger molecules to pass through
- Small proteins (e.g. albumins) leak out into the urine
106
What must be controlled during nephropathy?
Blood pressure, to decrease pressure within the kidney
107
What may nephropathy due to untreated diabetes result in?
Kidney failure, and the need for dialysis or a kidney transplant
108
Where is neuropathy due to uncontrolled diabetes primarily seen? What is it characterized by?
- Extremities, such as the feet
| - Stinging pain
109
What is a common way by which damage to blood vessels and tissues occur?
- Accumulation of advanced glycation-end products (AGEs)
- Ex: Hemoglobin A1c
- Glucose bound to the amino acids disrupt the functions of the proteins
110
What are potential physical complications due to untreated diabetes?
- Blindness
- Kidney failure and transplant
- Nerve pain
- Potential amputations
111
Which tissues can synthesize glucose from glycogen, and export glucose to other tissues? Why?
- The liver, kidney, and gut
| - Because they possess glucose-6-phosphatase
