Barbosa's Key Terms Flashcards
1
Q
What enzyme in glycolysis does fluoride inhibit?
A
Enolase; Water fluoridation reduces lactate production by mouth bacteria, decreasing dental caries
2
Q
What happens in exercising muscle when NADH production exceeds the oxidative capacity of the respiratory chain?
A
Pyruvate is reduced to lactate via lactate dehydrogenase
3
Q
Where is the reduction of pyruvate to lactate likely to happen?
A
Lens and cornea of eye, kidney medulla, testes, leukocytes and RBCs
4
Q
What causes cramps during intense exercise?
A
Lactate build-up in muscle lowers intracellular pH
5
Q
What is lactic acidosis?
A
Elevated [lactate] in plasma (a type of metabolic acidosis) where there is a collapse of circulatory system, such as MI, PE, and uncontrolled hemorrhage
6
Q
What is glycolysis?
A
The hub of carbohydrate metabolism
- ALL sugars can be converted to glucose
- End product = Pyruvate
7
Q
The glycolytic pathway is employed by ___ _____ for oxidation of glucose to provide _____ and ______ for other metabolic pathways.
A
all tissues; energy (ATP); intermediates
8
Q
What is the first step of glycolysis?
A
Phosphorylation of glucose
- Glucose -> G6-P
- Irreversible; traps sugar in cytosol
9
Q
What is the second step of glycolysis?
A
G6-P -> F6-P
-Enzyme: Phosphoglucose isomerase
10
Q
What is the most rate-limiting and committed step of glycolysis?
A
Step 3: F6P -> F 1,6-Bisphosphate
-enzyme: Phosphofructokinase-1 (PFK-1)
11
Q
What activates the phosphorylation of F6-P (step 3 of glycolysis)?
A
Fructose 2,6-Bisphosphate
AMP
Insulin
12
Q
What inhibits the phosphorylation of F6-P (step 3 of glycolysis)?
A
ATP
Citrate
Glucagon
13
Q
In step 4 of glycolysis, F 1,6-BisP is cleaved by ______ to _______ and ________.
A
Aldolase B; Glyceraldehyde 3-P; Dihydroxyacetone Phosphate (DHAP)
- Glyceraldehyde 3-Pi and DHAP can be converted to one another by Triose Phosphate Isomerase
- Aldolase B also cleaves dietary fructose
14
Q
What is the first oxidation-reduction reaction of glycolysis?
A
Step 5: Glyceraldehyde 3-P -> 1,3-BPG
-makes NADH
15
Q
What catalyzes step 6 of glycolysis (1,3-BPG -> 3-Phosphoglycerate)?
A
Phosphoglycerate kinase
-makes 1st ATP
16
Q
What steps of glycolysis use substrate level phosphorylation to make ATP?
A
Step 6 (1,3-BPG -> 3-Phosphoglycerate) Step 9 (Phosphoenolpyruvate -> Pyruvate)
17
Q
What is substrate-level phosphorylation?
A
Energy for production of high-energy P comes from substrate rather than ETC
18
Q
What is enolase responsible for?
A
In step 8 of glycolysis, dehydrates 2-Phosphoglycerate to Phosphoenolpyruvate (which is high-E)
19
Q
What is pyruvate kinase responsible for?
A
Formation of pyruvate, producing ATP (last step of glycolysis)
20
Q
What is the last step of glycolysis activated by?
A
Fructose 1,6-bisphosphate
Insulin
21
Q
What is the last step of glycolysis inhibited by?
A
Glucagon
22
Q
What is the net energy yield for anaerobic glycolysis?
A
2 ATPs for each glucose converted to 2 lactate
-No net production or consumption of NADH
23
Q
What is the net energy yield for aerobic glycolysis?
A
2 ATP per glucose
2 NADH -> about 3 ATP for each NADH
24
Q
What is a monosaccharide?
A
Simple sugars
25
What are monosaccharides classified by?
```
-Number of carbon atoms:
3 = trioses
4= tetroses
5 = pentoses
6 = hexoses
7 = heptoses
9 = nonoses
-Type of carbonyl group:
Aldehyde group = Aldose
Ketone group = Ketose
```
26
What is a disaccharide?
2 monosaccharides
27
What is lactose?
Disaccharide; galactose + glucose
28
What is sucrose?
Disaccharide; glucose + fructose
29
What is maltose?
Disaccharide; glucose + glucose
30
What is an alpha-1,4 bond?
Glycosidic bond that can link monosaccharides; links C1 of first sugar to C4 of 2nd sugar (makes straight lines)
31
What is an alpha-1,6 bond?
Glycosidic bond that can make branches
32
What is glycogen?
Important polysaccharide
- branched
- animal source
33
What is starch?
Important polysaccharide
- branched
- plant source
34
What is a glycoprotein?
Sugar attached to a protein
| -Sugar attached to noncarb via N- or O-glycosidic bond (-NH2 vs -OH group)
35
What kind of glycosidic bond does ATP have?
N-glycosidic
36
What kind of glycosidic bond does lactose have?
O-glycosidic
37
What kind of glycosidic bond does starch have?
O-glycosidic
38
What role does pancreatic alpha-amylase play?
Salivary alpha-amylase starts digestion in the mouth and breaks alpha(1->4) bonds, digestion stops in the stomach because high acidity inactivates salivary alpha-amylase; pancreatic alpha-amylase continues process in small intestine
39
What are dextrins?
Short, branched oligosaccharides produced by salivary alpha-amylase breaking down alpha(1-4) bonds in starch and glycogen
40
What does disaccharidase deficiency cause?
Passage of undigested carbs into large intestine -> osmotically active -> water drawn in -> osmotic diarrhea
- large volumes of CO2 and H2 gas cause abdominal cramps, diarrhea, and flatulence
- causes: genetic, intestinal diseases, malnutrition, and drugs that injure mucosa of small intestine
41
What is lactose intolerance and what population does it affect?
Lactase deficiency in small intestine -> lactose cannot be broken down into glucose and galactose -> lactose goes to large intestine and causes osmotic diarrhea
-more than 70% of world's adults, 90% african/asian descent
42
Where does gluconeogenesis occur? When does it occur?
90% in liver, 10% in kidneys; during times of fasting
43
What are the major precursors of gluconeogenesis?
Lactate, glycerol, amino acids (especially alanine)
44
Gluconeogenesis is the reversal of glycolysis besides which 3 key steps?
1) Pyruvate to phosphoenolpyruvate
2) F 1,6 BisP to F6-P
3) Glucose 6-P to Glucose
45
How is lactate produced?
Anaerobic glycolysis in exercising muscle and RBCs
46
What role does lactate dehydrogenase (LDH) play in gluconeogenesis?
Reversible enzyme; converts lactate to pyruvate (regenerating NADH)
47
What role does alanine aminotransferase (ALT) play in gluconeogenesis?
```
Converts alanine (from muscle stores) to pyruvate
-We measure ALT in liver function panel because it will be elevated in liver disease
```
48
What role does pyruvate carboxylase play in gluconeogenesis?
Carboxylates pyruvate to form oxaloacetate
- requires coenzyme biotin
- requires ATP
49
What role does phosphoenolpyruvate carboxykinase (PEPCK) play in gluconeogenesis?
Releases the CO2 from oxaloacetate (decarboxylation) to form phosphoenolpyruvate (PEP)
- GTP provides the energy
- There is mitochondrial and cytosolic PEPCK (50/50)
50
What important role does fructose 1,6-bisphosphatase play?
In gluconeogenesis this enzyme bypasses PFK-1 rxn (which is irreversible)
-Fructose 1,6-Bisphosphate ->Fructose 6-Phosphate
51
What important role does glucose 6-phosphatase play?
In gluconeogenesis this enzyme hydrolyzes Pi from G6-P -> free glucose
- NOT the reversal of glycolysis because ATP is not produced
- only found in the liver and kidneys
52
What is DHAP?
A glycolytic intermediate formed by glycerol -> glycerol 3-phosphate -> DHAP
53
What is the energy expenditure of gluconeogenesis?
Uses 6 ATP and 2 NADH/glucose
54
Increasing the concentration of Fructose 2,6-Bisphosphate would activate which pathway? And inhibit what pathway?
Glycolysis; Gluconeogenesis
-F2-6-BisP is a regulator of both glycolysis and gluconeogenesis. There are high levels of F2-6-BisP in well fed states when insulin is high and glucagon is low and therefore activates glycolysis. But in fasting states, where there is high glucagon it is present in low numbers and therefore inhibits glycolysis and gluconeogenesis can take place.
55
Increasing acetyl CoA would activate or inhibit gluconeogenesis?
Allosterically activate
56
Increasing AMP would activate or inhibit gluconeogenesis?
Allosterically inhibit
57
What 3 sources are blood glucose obtained from?
1) Diet
2) Degradation of glycogen
3) Gluconeogenesis
58
Describe the clear distinction between liver and muscle cells' glycogen stores.
Muscle: fuel reserve ("selfish")
Liver: maintain blood glucose during early stages of fast
59
What is glycogen?
Body mechanism for glucose storing, rapidly mobilizable from liver and kidney
-Muscle glycogen is extensively degraded in exercising muscle
60
Describe the structure of glycogen.
Branched chain, alpha-D glucose
- Primary glycosidic bond: alpha(1->4)
- After about 8-10 residues: branch alpha(1->6) linkage
- Polymers exist in discrete cytoplasmic granules that contain most enzymes for synthesis and degradation
61
What is the source of all glucosyl residues added to growing glycogen and how is it made?
UDP-glucose; made from G-1-P and UTP by UDP-Glucose pyrophosphorylase
62
What is the role of glycogenin?
It serves as a primer in glycogen synthesis
- Autocatalyzes primer formation from UDP-glucose
- Where glycogen synthase elongates from
- Contains tyrosine residue
63
What is the role of glycogen synthase?
Cannot initiate, only elongates from glycogenin, making alpha(1->4) linkages
-Transfer from UDP-glucose to nonreducing end of growing chain, forming new glycosidic bond between the anomeric hydroxyl group of C1 of activated glucose and C4 of accepting
64
What is the role of 4:6 transferase?
Formation of branches in glycogen
| -alpha(1->6) linkages
65
What is glycogenolysis and what is its primary product?
Degradation of glycogen (not the reversal of synthesis); G-1-P
66
What is the role of glycogen phosphorylase?
Sequentially cleaves alpha(1->4) in glycogenolysis
67
What is the role of 4:4 transferase?
Also known as "oligo-alpha(1->4)->alpha(1->4)-glucantransferase" in glycogenolysis breaks the last 3/4 alpha (1->4) bond and reattaches them to another alpha (1->4)
-remaining glucosyl residue attached in alpha(1->6) removed hydrolytically by amylo-alpha(1->6) glucosidase -> G1P
68
What is the role of phosphoglucomutase?
Converts G-1-P to G-6-P (in cytosol)
- in liver: transported into ER by G-6-P translocase and converted to free glucose by G 6-Phosphatase
- in skeletal muscle will enter glycolysis
69
What deficiency causes Glycogen Storage Disease (GSD)?
Deficiency of enzyme alpha(1->4)-glucosidase that functions in lysosomal degradation of glycogen
- causes accumulation of glycogen in vacuoles in lysosomes
- also called Type II: Pompe disease
70
What is the most common monosaccharide consumed by humans?
Glucose
| -also significant amounts of fructose and galactose
71
What is galactose?
Important component of structural carbohydrates
72
What percentage of our calorie intake is from fructose? What is the major source of fructose?
10% ; sucrose
| -also as a monosaccharide in fruits, honey, high-fructose corn syrup, soft drinks, foods
73
T or F: Fructose promotes insulin secretion.
False
74
What is fructose broken down into?
Cleaved by fructokinase and aldolase-B to glyceraldehyde and DHAP --> enters glycolysis
75
Where is sorbitol dehydrogenase found?
Liver, ovaries, seminal vesicles
76
How is glucose reduced to fructose?
Glucose (an aldosugar) reduced by Aldose Reductase to Sorbitol
Sorbitol -> Fructose (a ketosugar) by Sorbitol Dehydrogenase
77
Where is sorbitol found?
In lens, retina, Schwann cells of peripheral nerves, liver, kidney, placenta, RBCs, and cells of ovaries and seminal vesicles
78
What does hyperglycemia and sorbitol build-up cause?
Cataracts and peripheral neuropathy
- Blood glucose elevated -> Aldose Reductase increases [sorbitol] and remains trapped
- Sorbitol Dehydrogenase low -> Sorbitol accumulates -> strong osmotic effects (cell swelling, water retention)
79
Where does our major dietary source of galactose come from?
Lactose from milk producs
80
True or false: Transport of galactose into cells is not insulin dependent.
TRUE
81
What is the role of galactokinase?
Phosphorylates galactose -> galactose 1-phosphate
82
How is UDP-galactose converted to UDP-glucose?
By UDP-hexose 4-epimerase
| -an epimerase interconverts 2 epimers
83
UDP-galactose is a donor of galactose units in which synthetic pathways?
Lactose
Glycoproteins
Glycolipids
Glycosaminoglycans (GAGs)
84
Where is alpha-lactalbumin found? What is it stimulated by?
Only in mammary glands; stimulated by prolactin (in lactating females) to increase protein A's Km for glucose so that protein B will have a lower Km for galactose (more affinity)
-protein B will make lactose
85
What does lactose synthase make?
Galactosyl beta(1->4)-glucose or "milk sugar" (lactose)
- synthesized in golgi
- transfers galactose from UDP-galactose to glucose
86
What is the pentose phosphate pathway? Where does it take place?
"Hexose monophosphate shunt"; in cytosol
87
What does the PPP produce?
2 NADPH, ribose and CO2 for each G-6-P
| -No ATP consumed/produced
88
The testes, ovaries, placenta and adrenal cortex depend on NADPH for the biosynthesis of what?
Steroid hormones
89
Liver, lactating mammary glands, and adipose tissue depend on NADPH for the biosynthesis of what?
Fatty acids
90
The RBCs depend on NADPH to keep _____ reduced.
Glutathione
91
What happens in the first oxidative reaction of the PPP?
Dehydrogenation of G-6-P by G-6-PD -> 6-phosphogluconolactone
- irreversible step
- main regulated step
- makes 1st NADPH
92
What happens in the third oxidative reaction of the PPP?
Oxidative decarboxylation of 6-phosphogluconate -> Ribulose 5-phosphate
- irreversible step
- makes 2nd NADPH
93
What important glycolytic intermediates are formed from the reversible non-oxidative reactions of the PPP?
F-6-P and Glyceraldehyde-3-P
94
How does NADPH differ from NADH?
Only by -P on ribose; high-E molecule destined for reductive biosynthesis, rather than e- for transfer to oxygen
95
What are some of the uses of NADPH?
1) Reductive biosynthesis
2) Reduction of hydrogen peroxide
3) Cytochrome P450 monooxygenase system (synthesis of vitamin D3, bile, and steroid hormone)
4) Phagocytosis by WBCs
5) Synthesis of nitric oxide
96
How is NADPH used for reductive biosynthesis?
Fatty acids and chain elongation, cholesterol and steroids, NTs, nucleotides, superoxide
97
What are reactive oxygen species (ROS)?
Formed continuously as byproducts of aerobic metabolism, reactions with drugs and environmental toxins, or when levels of antioxidants is diminished -> oxidative stress
-from ok to super bad: oxygen, superoxide, hydrogen peroxide, hydoxyl radical
98
What do ROS damage?
DNA, proteins, lipids, cell death
| -implicated in cancer, inflammatory disease, and aging
99
How does reduced glutathione (G-SH) serve as protection against ROS?
A tripeptide-thiol (has 3 amino acids: glycine, cysteine and glutamate)
- chemically detoxify H2O2 by glutathione peroxidase
- reduced version will donate an e- to H2O2
100
What is the role of glutathione reductase?
After glutathione donates an e- to H2O2 it is oxidizes (and no longer protective), glutathione reductase regerates G-SH by using NADPH
101
What is NADPH used for in the cytochrome P450 monoxygenase system?
Biosynthesis of steroid hormones, detoxification of foreign compounds (xenobiotics), alcohol, vitamin D3, bile
102
What is the function of the NADPH oxidase?
Works with myeloperoxidase (MPO) to kill bacteria in the O2-dependent system
103
What is the most potent of bactericidal mechanisms?
MPO system (myeloperoxidase)
104
Once the micro-organism has been phagocytized by the phagolysosome in the O2-dependent system what occurs?
1) NADPH oxidase reduces O2 to superoxide
2) "respiratory burst" - rapid consumption of O2
3) Superoxide dismutase converts superoxide to H2O2
4) Peroxide + chloride -> HOCl (master killer aka bleach)
105
What functions is NO involved in?
1) Endothelium-derived relaxing factor: vasodilation by relaxing vascular smooth muscle
2) Neurotransmitter: prevents platelet aggregation
3) Role in macrophage function
106
Which NO synthase type will ultimately help the most with destruction of bacteria?
```
inducible NOS (iNOS)
-macrophages and neutrophils -> inducible large amounts defense against pathogens
```
107
What does G-6-PD deficiency cause?
Impairs the ability of RBC to form NADPH -> hemolysis
| -causes anemia
108
What are glycosaminoglycans (GAGs)?
Large complexes of negatively charged heteropolysaccharide chain
-special ability to bind a lot of water -> gel-like matrix
109
GAGs are associated with a small amount of core protein forming _______, typically ___% carbohydrates.
proteoglycans ; 95%
110
What do GAGs make up, along with fibrous structural proteins and adhesive proteins?
```
extracellular matrix (ECM)
-hydrated GAGs serve as flexible support for ECM
```
111
Describe the structure of glycosaminoglycans?
Long, unbranched, heteropolysaccharide chains of a repeating disaccharide unit (acidic sugar + an amino sugar)
112
How is hyaluronic acid different from other GAG?
Not sulfated, not covalently attached to protein and not limited to animal tissue
- serves as a lubricant and shock absorber
- monomers associate with hyaluronic acid to form proteoglycan aggregates through ionic interactions (non-covalent)
113
What are proteoglycans?
In ECM and outer cell surface; monomer in cartilage consists of core protein + 100 linear chains of GAGs
-separated by charge repulsion -> "bottle brush"
114
How are GAGs degraded?
Phagocytized by lysosomes and degraded with acid hydrolases
115
What are mucopolysaccharidoses?
Hereditary diseases caused by deficiency of any one of the lysosomal hydrolases characterized by lysosomal accumulation of GAGs in various tissues
116
Oligosaccharide components are typically ________ ___________ composed primaily of ___-hexoses.
branched heteropolymers; D
117
What kind of glycosidic link does asparagine have?
N-glycosidic link
118
What kind of glycosidic link does serine have?
O-glycosidic link
119
What kind of glycosidic link does threonine have?
O-glycosidic link
120
What is acetyl CoA?
A byproduct of metabolism; created by the conversion of pyruvate by pyruvate dehydrogenase complex.
- Enters the TCA cycle
- Contains 2 carbons
- Pyruvate gets decarboxylated, acetylated, and dehydrogenated in order to become acetyl CoA
121
What is glucoamylase?
Dietary enzyme that breaks down Galactose -> galactose-1-Phosphate during galactose metabolism
122
What is malate dehydrogenase?
Enzyme found in the TCA cycle that converts malate to oxaloacetate. It is also used in gluconeogenesis if there are no mitochondrial phophoenolpyruvate carboxykinases and the oxaloacetate has to be transferred out of the mitochondria
123
What is sucrase-isomalatase complex?
Disaccharides that breaks down sucrose into glucose and fructose alpha(1->2) bond that is found on the intestinal mucosa of the small intestine
