Biochemistry: Carbohydrates Flashcards
1
Q
ETC Complex I Inhibitors
A
BPAR
Barbiturates - CNS depressant
Piericidin A - NADH dehydrogenase inhibitor, antibiotic
Amytal - barbiturate derivative
Rotenone - pesticide
2
Q
ETC Complex II Inhibitors
A
MCT
Malonate - competitive inhibitor of the enzyme succinate dehydrogenase
Carboxin - fungicide
TTFA - Thenoyltrifluoroacetone, a chemical compound used pharmacologically as a chelating agent
3
Q
ETC Complex III Inhibitors
A
AD
Antimycin A - piscicide (fish poison)
Dimercaprol/BAL - also called British anti-Lewisite, is a medication used to treat acute poisoning by arsenic, mercury, gold, and lead
Complex III and/or IV inhibition: ETC will no longer work!
4
Q
ETC Complex IV Inhibitors
A
CCSH
Cyanide
Carbon monoxide
Sodium azide - gas-forming component in many car airbag systems
Hydrogen sulfide
Complex III and/or IV inhibition: ETC will no longer work!
5
Q
Examples of compounds that increase the permeability of the inner mitochondrial membrane to protons, ETC proceeds without establishing proton gradient
Name?
Effects?
Examples?
A
Name: Uncouplers
Effects: Increased oxygen consumption, decreased NADH/NAD and FADH/FAD ratio, decreased ATP synthesis
Examples: Synthetic - 2,4 dinitrophenol (pesticide), aspirin (hyperpyrexia in overdose leads to ETC uncoupling); Uncoupling protein - thermogenin (brown fat)
6
Q
ATP Synthase Inhibitor
A
a. k.a. Complex V Inhibitors
ex. Oligomycin - a macrolide
7
Q
GLUT 1 transporter found in
A
Brain Colon Kidney Placenta RBCs
Glucose uptake
8
Q
GLUT 2 transporter found in
A
Kidney
Liver
Pancreas
Small intestine (BM)
Rapid uptake or release of glucose
9
Q
GLUT 3 transporter found in
A
Brain
Kidney
Placenta
Glucose uptake
10
Q
GLUT 4 transporter found in
A
Adipose tissue
Heart muscle
Skeletal muscle
Insulin-stimulated glucose uptake
11
Q
GLUT 5 transporter found in
A
Small intestine (lumen)
Absorption of glucose
12
Q
SGLT 1 transporter found in
A
Kidney
Small intestine
Sodium-dependent active uptake of glucose against a concentration gradient
13
Q
What is the rate-limiting step and associated enzyme in glycolysis?
A
Fructose-6-phosphate –> Fructose-1,6-bisphosphate
Enzyme: Phosphofructokinase-1 (PFK-1)
14
Q
What is glycolysis for?
A
Major pathway for glucose metabolism that converts glucose into 3 carbon compounds to provide energy
15
Q
Where does glycolysis occur?
A
In the cytosol of all mammalian cells
16
Q
What is the substrate of glycolysis?
A
Glucose
17
Q
What are the end-products of glycolysis?
A
2 molecules of either pyruvate or lactate
18
Q
Fates of Pyruvate (3 carbons)
Process, Enzyme, Product
A
- Gluconeogenesis, Pyruvate carboxylase (4 carbons), Oxaloacetate
- Citric acid cycle, Pyruvate dehydrogenase complex (2 carbons), Acetyl CoA
- Fermentation, Pyruvate decarboxylase, Ethanol
- Anaerobic glycolysis, Lactate dehydrogenase, Lactate
19
Q
Coenzymes (essential co-factors) in Pyruvate –> AcetylCoA
A
Thiamine phosphate (Vitamin B1) FAD (Vitamin B2) NAD+ (Vitamin B3) Coenzyme A (contains pantothenic acid, Vitamin B5) Lipoic acid (Arsenic binds to this)
20
Q
Glycolysis clinical correlates:
Deficiency of which enzyme causes hemolytic anemia?
A
Aldolase A
21
Q
Glycolysis clinical correlates:
Most common enzyme defect in glycolysis, causes Congenital hemolytic anemia
A
Pyruvate kinase
Step 10: Phosphoenolpyruvate –> Pyruvate
22
Q
Glycolysis clinical correlates:
Low exercise capacity, especially on high carbohydrate diets, Step 3
A
(Fructose 6 phosphate –> Fructose 1,6 bisphosphate + ADP)
(Muscle) phosphofructokinase 1
23
Q
Glycolysis clinical correlates:
Pyruvate dehydrogenase deficiency causes ___, treat with
A
Congenital lactic acidosis
Ketogenic diet, since increase in lactate plus decreased AcetylCoA leads to psychomotor retardation and death
24
Q
Glycolysis clinical correlates:
Requires treatment during pregnancy and is caused by mutations that decrease activity of glucokinase
A
Maturity Onset Diabetes in the Young Type 2 (MODY 2)
25
Glycolysis clinical correlates:
| Competes with inorganic phosphate as a substrate for glyceraldehyde 3P dehydrogenase, no NADH and no ATP is produced
Arsenic poisoning
26
Glycolysis clinical correlates:
| Causes potentially fatal pyruvic and lactic acidosis, inhibits thiamine absorption
Chronic alcoholism
27
Classic amphibolic pathway
| Final common pathway for the metabolism of carbohydrates, lipids and proteins
Citric acid cycle/ Tricarboxylic acid cycle/ Krebs cycle
28
What is the citric acid cycle for?
Major pathway for ATP formation
| Provides the substrates for gluconeogenesis, amino acid and fatty acid synthesis
29
Where does the citric acid cycle occur?
In all cells with mitochondria
All ingredients needed are in the mitochondrial matrix, except for succinate dehydrogenase which is in the inner mitochondrial membrane
30
What is the substrate of the citric acid cycle?
Acetyl CoA
31
What are the end-products of the citric acid cycle?
1 - FADH2
1 - GTP
2 - CO2
3 - NADH
32
What is the rate-limiting step and associated enzyme in the citric acid cycle?
Isocitrate --> alpha ketoglutarate
| Enzyme: Isocitrate dehydrogenase
33
What is the rate-limiting step and associated enzyme in the citric acid cycle?
Isocitrate --> alpha ketoglutarate
| Enzyme: Isocitrate dehydrogenase
34
Enzymes that produce NADH/FADH
All are dehydrogenases!
1. Isocitrate dehydrogenase (isocitrate to alpha ketoglutarate)
2. Alpha ketoglutarate dehydrogenase (alpha ketoglutarate to succinyl CoA)
3. Succinate dehydrogenase (succinate to fumarate) --> the only FADH producing
4. Malate dehydrogenase (malate to oxaloactetate)
35
Products in the steps of the citric acid cycle
Cindy Is Kind So She Forgives More Often
```
Citrate
Isocitrate
(alpha) Ketoglutarate
Succinyl CoA
Succinate
Fumarate
Malate
Oxaloacetate
```
36
What is gluconeogenesis for?
Process of synthesizing glucose from non-carbohydrate precursors, in order to prevent hypoglycemia during a fast
37
Where does gluconeogenesis occur?
Mitochondria and cytosol
90% in the liver
10% in the kidney
*40% in kidney if prolonged fast, hence hypoglycemia in renal failure patients
38
What are the substrates of gluconeogenesis?
Intermediates of glycolysis and the TCA, except for Acetyl CoA
Glycerol and propionyl CoA from triacylglycerols
Lactate through the Cori cycle
Carbon skeletons of glucogenic amino acids
39
What is the product of gluconeogenesis?
Glucose
40
What is the rate-limiting step and its enzyme in gluconeogenesis?
Fructose 1,6 bisphosphate --> Fructose 6 phosphate
| Enzyme: Fructose 1,6 bisphosphatase
41
What do steps 1 and 2 of gluconeogenesis reverse in glycolysis?
Step 1: Pyruvate --> Oxaloacetate
Enzyme: Pyruvate carboxylase
Step 2: Oxaloacetate --> Phosphoenol pyruvate
Enzyme: Phosphoenolpyruvate carboxykinase
Reverses Step 10: pyruvate kinase which converts phosphoenolpyruvate to pyruvate
42
What do carboxylases do and what is the required co-factor?
Attach a carbon atom using CO2 as a substrate, require biotin as a co-factor
43
What does step 9 of gluconeogenesis reverse in glycolysis?
Fructose 1,6 bisphosphate --> Fructose 6 phosphate
Enzyme: Fructose 1,6 bisphosphatase
Reverses step 3: Phosphorylation of Fructose 6 phosphate to Fructose 1,6 bisphosphate by PFK 1
44
What does step 11 of gluconeogenesis reverse in glycolysis?
Glucose 6 phosphate --> Glucose
Enzyme: Glucose 6 phosphatase
Step shared with glycogenolysis, so glucose may exit the cell and enter bloodstream
Reverses step 1: Glucose to glucose 6 phosphate by enzyme hexokinase
45
What is the Cori cycle?
Occurs in the liver, lactate from skeletal muscle is converted back to glucose through gluconeogenesis
46
What is the significance of the Cori cycle?
Prevent lactic acidosis in the muscles
47
What regulates gluconeogenesis?
1. Circulating levels of glucagon
2. Availability of glucogenic substrates
3. Allosteric activation of hepatic pyruvate carboxylase by acetyl CoA
4. Allosteric inhibition of fructose 1,6 bisphosphatase by AMP
48
Where does the energy used in gluconeogenesis come from?
Fatty acid oxidation a.k.a. beta oxidation
49
What is the energy requirement of gluconeogenesis?
1. Cleavage of 6 high energy phosphate bonds
| 2. Oxidation of 2 NADH
50
Clinical correlates of gluconeogenesis:
| Excessive gluconeogenesis in response to injury and infection
Hyperglycemia in critically ill patients (stress hyperglycemia)
51
Clinical correlates of gluconeogenesis:
| Another state of excessive gluconeogenesis, glucose spills out in another fluid other than plasma
Glucosuria
52
Clinical correlates of gluconeogenesis:
| Hypoglycemic states and their description
Hypoglycemia during pregnancy - high fetal glucose consumption
Hypoglycemia in neonates - premature and LBW infants (little adipose tissue, undeveloped enzymes for gluconeogenesis)
Hypoglycemia in alcoholics - high amounts of cytoplasmic NADH from alcohol metabolim, intermediates of gluconeogenesis are diverted into alternate pathways, less glucose synthesis
53
Branched polymer of alpha-D-glucose
Glycogen
Branched for more efficient breakdown
Primary glycosidic bond: horizontal bond = alpha 1-4
Secondary bond: vertical bond = alpha 1-6
54
What is glycogenesis for?
Synthesis of glycogen during the well-fed state
55
Where does glycogenesis occur?
Cytosol of liver and muscle
56
What is the substrate of glycogenesis?
alpha-D-glucose
57
What is the product of glycogenesis?
Glycogen
58
What is the rate-limiting step in glycogenesis
Elongation of glycogen chains (creation of alpha 1-4 glycosidic bonds)
Enzyme: Glycogen synthase
59
Protein that serves as a primer for glycogen synthesis when glycogen is completely depletes
Glycogenin
Without this, residual glycogen fragments can accept glucose residues
60
What is the role of UDP glucose in glycogenesis?
Source of glucosyl residues that are added to the glycogen molecule ("Yaya", ihahatid si glucose para humaba si glycogen)
Enzymes: phosphoglucomutase, UDP-glucose pyrophosphorylase
61
Component and function of branching enzymes in glycogenesis
Amylo alpha 1-4 --> alpha 1-6 transglucosidase
Forms new alpha 1-6 bonds by transferring 5 to 8 glucosyl residues
62
What is glycogenolysis for?
Mobilization of stored glycogen during fasting state
63
Where does glycogenolysis occur?
Cytosol of liver and muscle
64
What is the substrate in glycogenolysis?
Glycogen
65
What are the products in glycogenolysis?
Glucose in liver
| Glucose 6 phosphate in muscle
66
What is the rate-limiting step in glycogenolysis?
Shortening of glycogen chains
| Enzyme: Glycogen phosphorylase
67
What is the coenzyme for shortening of glycogen chains? What is the enzyme?
Co-enzyme: Pyridoxal phosphate
| Enzyme: Glycogen phosphorylase
68
What is "limit dextrin"?
Last 4 glucosyl units remain in the shortening of glycogen chains, stop signal for glycogenolysis
69
Component and function of debranching enzymes in glycogenolysis
alpha 1-4 --> alpha 1-4 glucantransferase, amylo alpha 1-4 glucosidase
Cleavage of alpha 1-4 and alpha 1-6 bonds, yields free glucose from the cleavage of the alpha 1-6 bond
70
Glycogenolysis end products and enzymes for their conversion
Enzymes: phosphoglucomutase, and when present, glucose 6 phosphatase
End products:
Liver: glucose
Muscle: glucose 6 phosphate
71
Function of alpha 1-4 glucosidase or acid maltase
Lysosomal degradation of glycogen (1-3% of glycogen)
| Enzyme deficiency leads to Pompe disease
72
Presentation of glycogen storage diseases
Abnormal glycogen metabolism
Accumulation of glycogen in cells
12 types, due to enzyme deficiencies
73
Deficiency in glucose 6 phosphatase
Disease
Clinical features
Von Gierke Disease (GSD Ia)
```
Increased glycogen in renal tubule cells and liver
Hepatomegaly
Hypoglycemia (severe)
Lactic acidosis
Ketosis
Hyperlipidemia
```
74
Deficiency in lysosomal acid maltase
Disease
Clinical features
Pompe Disease (GSD II)
Increased glycogen in lysosomes
Juvenile onset: hypotonia, death from heart failure by age 2
Adult onset: muscle dystrophy
75
Deficiency in debranching enzyme
Disease
Clinical features
Cori Disease (GSD IIIa)
Fasting hypoglycemia
Hepatomegaly in infancy
Muscle weakness
Increased limit dextrin
76
Deficiency in branching enzyme
Disease
Clinical features
Andersen Disease (GSD IV)
Hepatosplenomegaly
Increased polysaccharide with few branch points
Death from heart or liver failure by age 5
77
Deficiency in muscle phosphorylase
Disease
Clinical features
McArdle Syndrome (GSD V)
Poor exercise tolerance
Muscle cramps and myoglobinuria but no lactic acidosis
Increased muscle glycogen (unable to use)
78
Deficiency in liver phosphorylase
Disease
Clinical features
Hers Disease (GSD VI)
Hepatomegaly
Hypoglycemia (Mild)
79
Phosphorylation of galactose
Step
Enzyme
Clinical manifestation
Galactose --> Glucose 1 phosphate (becomes glucose 6 phosphate to enter glycolysis)
Galactokinase
Galactokinase deficiency
80
Formation of UDP galactose
Step
Enzyme
Clinical manifestation
Galactose 1 phosphate + UDP glucose --> UDP galactose + Glucose 1 phosphate
Galactose 1 phosphate uridyl transferase (GALT)
Classic galactosemia
81
Use of galactose as a carbon source
Step
Enzyme
UDP-galactose --> UDP glucose
UPD hexase 4 epimerase
82
Galactokinase deficiency
Clinical presentation
Treatment
Benign
Galactosemia and glactosuria
Cataracts in early childhood
Eliminate sources of galactose from diet
83
Classic galactosemia
(galactose 1 phosphate uridyl transferase deficiency)
Clinical presentation
Treatment
```
Toxic
Galactosemia and galactosuria
Diarrhea, vomiting, jaundice
Poor growth, severe mental retardation and liver damage in children
Premature ovarian failure in females
```
Eliminate sources of galactose from the diet
Prenatal diagnosis is possible
Newborn screening is available
84
```
Phosphorylation of fructose
Step
Enzyme
Clinical presentation
Treatment
```
Fructose --> Fructose 1 phosphate
Fructokinase or hexokinase
Essential fructosuria: Benign and asymptomatic
85
```
Formation of DHAP and Glyceraldehyde
Step
Enzyme
Clinical presentation
Treatment
```
Fructose 1 phosphate --> DHAP + Glyceraldehyde
```
Aldolase B
(Aldolase A is in Glycolysis: reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate)
```
Hereditary fructose intolerance (fructose only requires facilitated diffusion):
Profound hypoglycemia and vomiting after consumption of fructose or sucrose
Jaundice, hemorrhage, hepatomegaly, liver failure, renal dysfunction, hyperuricemia, lactic acidosis, death
Symptoms appear after weaning from milk
Eliminate sources of fructose, sucrose and sorbitol from diet
86
Conversion of glucose to sorbitol
Step
Enzyme
Location
Glucose --> Sorbitol (reduction reaction, lose H)
Aldose reductase
Lens, retina, Schwann cells, liver, kidney, placenta, RBC, ovaries, seminal vesicles
87
Conversion of sorbitol to fructose
Step
Enzyme
Location
Sorbitol --> Fructose
Sorbitol dehydrogenase
Liver, ovaries, seminal vesicles
88
Lactose intolerance
Enzyme deficiency
Clinical presentation
Treatment
Lactase deficiency
Flatulence and diarrhea after ingestion of dairy products
(osmotic laxative)
90% of Asians and Africans
Reduce consumption of milk but may eat yogurt, cheese, brocolli for adequate calcium intake
Lactase-treated or containing products
89
Sucrase-isomaltase complex deficiency
Clinical presentation
Treatment
Intolerance of ingested sucrose
10% of Inuits in Greenland and Canada
Dietary sucrose restriction
Enzyme replacement therapy
90
Why can guinea pigs and primates not produce ascorbic acid?
Lack of L-gulonolactone oxidase
91
Alternative pathway for glucose oxidation in the liver
Does not produce ATP
Produce glucoronic and iduronic acid
Uronic Acid Pathway
92
Essential component of GAGs
| Required in the detoxification of insoluble compounds such as bilirubin, steroids, morphine and other drugs
Glucuronic acid
93
Essential pentosuria
Enzyme deficiency
Clinical presentation
Treatment
Xylulose reductase deficiency
Increased urinary xylulose
Benign with no clinical consequence
94
A.k.a. Hexose monophosphate shunt
Pentose phosphate pathway
95
What is the pentose phosphate pathway for?
NADPH production - it is a cofactor for many enzymes
Produces ribose 5 phosphate needed for nucleotide biosynthesis
Metabolic use of 5-carbon sugars
Does not consume nor produce ATP
96
Where does the pentose phosphate pathway occur?
Cytosol of RBCs and tissues that produce lipids (liver, adipose tissue, adrenals, thyroid, testes, lactating mammaries)
97
What is the substrate in the pentose phosphate pathway?
Glucose 6 phosphate
98
What are the products of the pentose phosphate pathway?
NADPH
| Ribose 5 phosphate
99
What is the rate limiting step in the pentose phosphate pathway?
Glucose 6 phosphate --> 6 phosphogluconate
| Enzyme: Glucose 6 phosphate dehydrogenase
100
First phase of the pentose phosphate pathway
Oxidative? Reversible?
Key enzyme
Products
Oxidative, Irreversible
Glucose 6 phosphate dehydrogenase
2 NADPH, Ribulose 5 phosphate
101
First phase of the pentose phosphate pathway
Oxidative? Reversible?
Key enzyme
Products
Non-oxidative, Reversible
Transketolases, Co-factor: Vit B1
Ribose 5 phosphate
Fructose 6 phosphate
Glyceraldehyde 3 phosphate
Other carbohydrates
102
5 functions of NADPH
1. Reductive biosynthesis of fatty acids and steroids
2. Glutathione reduction in RBCs
3. Cytochrome P450 monooxygenase system
4. Oxygen-dependent bactericidal mechanism of WBCs
5. Synthesis of nitric oxide
103
Glutathione precursors
Glycine
Cysteine
Glutamate
104
What does glutathione peroxidase do?
Catalyzes removal of H2O2 by reduced glutathione
105
What is the enzyme for reduction of gluatathione?
Glutathione reductase, requires NADPH
106
Most common disease-producing enzyme deficiency in humans
| Clinical presentation?
G6PD Deficiency
Hemolytic anemia after oxidative stress (poor RBC defense against oxidizing agents)
Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. Complications can include anemia and newborn jaundice.[2] Some people never have symptoms.
It is an X-linked recessive disorder
107
Precipitating factors of G6PD deficiency disease
Infection (most common)
Drugs (sulfonamides, primaquine, chloramphenicol)
Fava beans
108
Pathologic findings in G6PD deficiency
Heinz bodies - altered hemoglobin that precipitates in RBCs
| Bite cells - abnormally shaped RBCs due to phagocytic removal of Heinz bodies in spleen
109
Chronic Granulomatous Disease
Enzyme deficiency
Clinical presentation
NADPH oxidase deficiency - no superoxide formation needed by leucocytes to induce oxidative damage to bacteria
Severe, persistent chronic pyogenic infections caused by catalase-positive bacteria --> Gram (+) bacteria, just walled off in granuloma, not killed
