MBOD block 4 Flashcards
(175 cards)
2
Q
What is metabolism?
A
The sum of all of the chemical reactions that can occur in a living organism.
3
Q
What is the function of metabolism?
A
To supply all of the needs of every cell.
4
Q
What are examples of anabolic pathways?
A
Biosynthetic pathways; Detoxification and waste disposal pathways.
5
Q
What are examples of catabolic pathways?
A
Fuel storage pathways; Fuel oxidative pathways
6
Q
What are some of the products of anabolic pathways?
A
Uric Acid, Urea, waste products
7
Q
What are some of the products of catabolic pathways?
A
Energy, CO2, H20, ATP
8
Q
What are some dietary fuels?
A
Carbohydrate, Fat, Protein
9
Q
What are the categories of Metabolic pathways?
A
Anabolic (biosynthetic); Catabolic (degradative); ATP-synthesizing pathways.
10
Q
What occurs in ATP-synthesizing pathways?
A
Energy released by oxidative catabolic reactions is used to synthesize ATP and other high energy compounds
11
Q
What things occur during the transformation of ATP to ADP in the ATP-ADP cycle?
A
Motion, Active transport, biosyntheses, signal amplification
12
Q
What things occur during the transformation of ADP to ATP in the ATP-ADP cycle?
A
Oxidation of fuel molecules, breakdown of sugars, photosynthesis
13
Q
The breakdown of ATP to AMP produces what products?
A
Pyrophosphate -> 2Pi
14
Q
What are carbohydrates, fats, and proteins oxidized to?
A
CO2, H2O, energy, (urea-proteins)
15
Q
Which compound has the highest standard free energy?
A
Phosphate Enol pyruvate
16
Q
What is an example of enol phosphate bond?
A
Phosphoenolpyruvate
17
Q
What is an example of an anhydride bonded to carbon?
A
1,3-bisphosphoglycerate
18
Q
What is creatine phosphate?
A
An activated carrier that stores energy in muscle.
19
Q
What is an example of an anhydride bonded to phosphate?
A
ATP
20
Q
Which compound has a phosphoester bond?
A
Glucose 6-phosphate
21
Q
What are some of the uses of ATP?
A
Protein synthesis, Na/K ATPase, Ca ATPase, Gluconeogenesis, Urea synthesis, Myosin ATPase, RNA synthesis, substrate cycling.
22
Q
What is a metabolic pathway?
A
A series of reactions leading from the transformation of one metabolite to another.
23
Q
What is an enzyme catalyzed reaction?
A
The product of one enzyme becomes the substrate for the next enzyme.
24
Q
T/F All pathways are linked and regulated.
A
TRUE
25
Q
T/F Pathways are irreversible.
A
TRUE
26
How many irreversible steps are there in every pathway?
At least one
27
What is the slowest step in a pathway?
The rate limiting step
28
What is the committed step?
The first irreversible step unique to a pathway.
29
What are the tupes of metabolic pathways?
Linear, branched, cyclic, cascade/amplification
30
What are the characteristics of a linear pathway?
One substrate, one product
31
What is the characteristic of a branched pathway?
Multiple products
32
What are the characteristics of a cyclic pathway?
Pathway starts and ends with the same compound; molecules enter and leave the cycle.
33
What are some examples of a cascade or amplification pathway?
Signal transduction, blood clotting
34
How do you control the pathways?
By regulating the activity of enzymes or the amount of an enzyme.
35
What are types of regulation or control of enzymes and metabolic pathways?
Allosteric control; feedback inhibition; reversible covalent modification
36
What is required for metabolic pathways?
Cofactors (NADH, FADH2, THF, Vit.D,C,K,A
37
T/F Each tissue has its own unique metabolism.
TRUE
38
What is glucose 6-phosphate a precursor to?
Nucleotides
39
What is fructose 6-phosphate a precursor to?
Amino sugars, glycolipids, glycoproteins
40
What is dihydroxyacetone phosphate a precursor to?
Lipids
41
What is 3-phosphoglycerate a precursor to?
Serine
42
What is pyruvate a precursor to?
Alanine
43
What is citrate a precursor to?
Cholesterol, fatty acids
44
What is oxaloacetate a precursor to?
Aspartate, amino acids, purines, pyrimidines
45
What is a-ketoglutarate a precursor to?
Glutamate, amino acides, purines
46
What is succinyl CoA a precursor to?
Heme chlorophyll
47
What is the first stage of Metabolism?
Breakdown of macromolecules to monomers.
48
What is the 2nd stage of Metabolism?
Breakdown of simple subunits to Acetyl CoA accompanied by production of limited amounts of ATP and NADH
49
What is the 3rd stage of Metabolism?
Complete oxidation of Acetyl CoA to H2O and CO2 accompanied by production of large amounts of ATP in the mitochondrion
51
What are the functions of carbohydrates?
Nutritional roles; source of energy; energy storage; vitamins; non-nutritive dietary role; structural component; molecular recognition
52
What is the major dietary carbohydrate?
Starch; followed by disaccharides
53
What is the source of energy that can be used by all tissues?
Glucose
54
What do mammals stroe glucose as?
Glycogen
55
Which vitamin is a carbohydrate?
Vitamin C
56
What is a nondigestible carbohydrate and what is its role?
Fiber; important in normal digestion
57
What are carbohydrates a structural component of?
cofactors; DNA/RNA; glysoproteins; glycolipids; proteoglycans; bacterial cell wall; cellulose
58
How are carbohydrates involved in molecular recognition?
Receptors; adhesion molecules; cell surface markers; soluble and membrane glycoproteins; glycolipids
59
What is the blood glucose concentration a balance of?
Pathways that use blood glucose and those that add glucose back to the blood.
60
Which hormones play a major role in controlling blood glucose conc.?
Insulin and glucagon
61
What is the normal blood glucose concentration?
100mg/dL
62
What happens to the insulin/glucagon ratio after a high carbohydrate meal?
The ratio increases.
63
What does the balance of metaboiic homeostasis depend on?
Fuel availability and Tissue needs
64
What are the 3 signals used to maintain metabolic homeostasis?
Blood level of nutrient; hormone level; nerve impulse
65
What are the pathways and reactions that increase blood glucose?
Digestion of dietary carbs; conversion of other dietary sugars to glc; glycogenolysis; gluconeogenesis
66
What are the pathways that use blood glucose?
Glucose transporters and phosphorylation; glycolysis; glycogenesis; phosphogluconate pathway; sorbitol pathway (aldose reductase).
67
What is the key glucoregulatory hormone?
Insulin
68
What is insulin?
An anabolic hormone; synthesized by the pancreatic beta-cells of the Islets of Langerhans as a single chain- pre-proinsulin ->proinsulin -> insulin and C-peptide
69
What does insulin do?
Stimulates glucose storage and uptake my muscle and adipose tissue; increases hepatic glycogenesis and lipogenesis.
70
What are the counter-regulatory hormones?
Glucagon; epinephrine; cortisol; growth horm.
71
What does glucagon do?
Increases blood glucose by stimulating glycogenolysis and gluconeogenesis.
72
Where is glucagon synthesized?
By the alpha cells of the pancreas.
73
What enhances the secretion of glucagon?
Hypoglycemia
74
What does epinephrine do?
Stimulates glycogenolysis and adipose tissue lipolysis. Inhibits insulin secretion.
75
What is epinephrine secreted in response to?
Stress
76
What is secretion of epinephrine enhanced by?
Hypoglycemia
77
What does cortisol do?
Stimulates glucagon release; stimulates gluconeogenesis
78
When is growth hormone secreted?
In hypoglycemia
79
What does growth hormone do?
Increases hepatic glucose production and reduces glucose use by some tissues.
80
What are disorders of blood glucose?
Hypoglycemia; Diabetes; Hyperglycemia
81
What is hypoglycemia?
Low blood sugar.
82
What is hypoglycemia caused by?
Impaired hepatic glycogenolysis or gluconeogenesis, excessive cellular uptake of glucose or excessive insulin secretion by insulin-secreting tumors, or administration of inappropriately high doses of insulin; excessive alcohol consumption.
83
What does the metabolism of alcohol do?
Increases NADH in the liver, which inhibits gluconeogenesis. Disrupts the NADH/NAD+ ratio, which affects reactions.
84
What is the normal of glucose concentration?
70-100 mg/dL
85
What is mild hypoglycemia?
BG less than 68mg; results in decreased glc uptake by the brain. Symptoms include feeling shaky, nervous, hungry, sweaty.
86
What is mild to moderate hypoglycemia?
Blood glucose less than 49mg%; results in cognitive dysfunction. Symptoms include headache, mood change, confusion, rapid heart beat.
87
What is severe hypoglycemia?
Usually requires assistance; may lose consciousness and require an injection of glucagon or dextrose.
88
What is Type 1 diabetes?
A deficiency of insulin
89
What is Type 2 diabetes?
Decreased secretion of insulin or reduced ability to respond to insulin.
90
What does the exposure of red blood cells to hyperglycemia result in?
Nonenzymatic glycosylation of hemoglobin forming hemoglobin A1c.
91
What is imparied glucose tolerance?
An asymptomatic condition that is diagnosed on the basis of an OGTT, the blood glucose values being intermediate between normal and diabetic.
92
What are ways used to measure glucose?
Blood glucose assays; reduction methods; glucose oxidase assay; hexokinase assay; urine glucose assays; glucose oxidase dipsticks
93
How does a glucose oxidase assay work?
Its highly specific for glucose; catalyzes the conversion of glucose to gluconic acid by oxygen, and forms H2O2, which reacts with an organic chromogen to form a colored product.
94
How does a hexokinase assay work?
Specific and accurate glucose method "Gold standard"; HK forms Glc-6-P; G-6-P dehydrogenase catalyzes the oxidation of G-6-P and reduces NADP+ to NADPH which is measured at 340nm.
95
What is glycosuria?
The presence of significant quantities of glucose in urine; blood glucose >160-180 mg/dL; decreased renal tubular reabsorption.
96
What are dipsticks?
Used for urinalysis; sticks with several small pads attached that contain chemicals that react with substances found in urine and gives a color change.
98
What are the characteristics of the epithelium?
Polarized, tight junctions, apical membrane, basolateral membrane.
99
What do the epithelial cells control the passage of?
Substances between the intestinal lumen and the milieu interieur
100
What is able to pass through tight junctions?
Only very small molecules.
101
T/F The distal epithelium is tighter than the proximal epithelium.
TRUE
102
What are the control mechanisms for absorption?
The intracellular transport pathways.
103
What creates the osmotic gradient that facilitates the movement of water into the lumen?
The digestion of ingested food.
104
What do active mechanisms involve?
The secretion of electrolytes into the lumen
105
How does the excess Cl- move out of the cell into the intestinal lumen?
Through the Cysic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl-channel.
106
What does the movement of excess Cl through the channel do?
Puts an osmotically active ion in the lumen; creates a greater negative charge in the lumen relative to the interstitium.
107
What does the negative charge in the lumen do?
It attracts another osmotically active ion, Na+ to move through the tight junctions.
108
What attracts water to move through the tight junctions?
The increase in osmotically active molecules in the lumen
109
What are the ways in which sodium moves into the epithelial cells?
Leakiness/Na-channels; cotransport with another molecule
110
What prevents an electrically depolarizing accumulation of Na+ in the epithelial cell?
NA+-K+ATPase on the basolateral membrane pumps the Na+ from the cell.
111
How does water move?
Paracellularly by passive diffusion; and facilitated transport through active and regulated water channels-aquaporins (AQP1, AQP3, AQP4)
112
Which carrier transports one molecule of sugar with two Na+?
Solute carrier family 5 member 1 (SLC5A1)
113
What does the sugar diffuse down its concentration gradient through?
A facilitated transport mechanism mediated by the protein coded for by the solute carrier family 2 member 2 gene (SLC2A2) that resides in the basolateral membrane.
114
What does fructose use to move from the lumen into the epithelial cell?
Solute carrier family 2 member 5 (SLC2A5) and SLC2A2
115
How are the ingested proteins broken down?
By the action of secreted peptidases, resulting in amino acids, di-, and tri-peptides.
116
How are di - and tri- peptides transported?
In a H+ dependent cotransport mechanism by the peptide transporter coded for by the solute carrier family 15 member 1 gene (SLC15A1)
117
What does emulsification do?
Disperse triglycerides and makes them more accessible for hydrolysis to monoglycerides.
118
What is the structure of micelles?
A hydrophobic interior with the hydrophilic carboxylates and glycerol backbones facing the hydrophilic environment.
119
How are fatty acids transported?
By binding ot the Fatty Acid Binding Protein (FABP2); and by the Fatty Acid Transport Protein 4 (SLC27A4 gene product)
120
How is Iron, in its ferric form, converted to the ferrous form in the duodenum?
By the action of ferroreductase.
121
What is iron transported into the epithelial cell by?
The protein coded by the solute carrier family 11 member 2 gene SLC11A2/NRAM2/DMT1
122
What does the SLC11A2 protein-mediated transport require?
An acidic environment.
123
What acts as an iron store in periods of abundance?
Ferritin
124
During periods of limited iron availability, there is increased synthesis of what two proteins?
SLC40A1/ferroportin; and TF
125
What is the role of SLC40A1?
Transports iron out of the epithelial cell.
126
What is the role of TF?
Binds the iron to transport it in the blood.
127
How does Ca enter the duodenal epithelial cells when it is not abundant?
In an electrochemically favorable direction through TRPV5 and TRPV6 Ca channels
128
What removes the Ca that enters the cells on the basolateral membrane?
Ca2+-ATPase and Na+-Ca2+ exchange, SLC8A1; secondary active transport mechanism
129
T/F Phosphate absorption is similarly both passive and active.
TRUE
130
How does the passive absorption of phosphate occur?
It is paracellular.
131
How does the active absorption of phosphate occur?
Through Na+-H2PO4- cotransport; SLC34A2
133
What areas do the portal system drain?
The distal end of the esophagus, stomach, small and large intestines, proximal portion of the rectum, pancreas, and spleen.
134
T/F The liver receives both nutrient-rich deoxygenated blood (portal vein) and oxygenated blood (hepatic arteries).
TRUE
135
What is the role of hepatocytes?
Detoxifies the blood, metabolizes fats, carbohydrates, and drugs, and produce bile.
136
What receives the deoxygenated and oxygenated blood?
The sinusoids
137
How does the blood exit the sinusoids?
Into a central vein, into the IVC
138
Why is the concentration of oral drugs reduced before entering the systemic circulation?
Because of hepatic metabolism; First-pass effect
139
How is the proximal portion of the rectum drained?
Via the superior rectal vein -> inferior mesenteric vein
140
How is the remainder of the rectum drained by?
The middle rectal vein; inferior rectal vein
141
What are the routes of drug administration?
Intravenous; Subcutaneous; Intramuscular; Oral Ingestion
142
What is the most common, safest, convenient, and economical method of drug administration?
Oral ingestion
143
What are some disadvantages to the oral route?
Limited absorption; emesis; destruction of some drugs by digestive enzymes or low gastric pH; irregularities in absorption or propulsion in the presence of food or other drugs; cooperation of the part of the patient.
144
What is bioavailability?
The fraction of unchanged drug reaching the systemic circulation following administration by any route
145
T/F The area under the blood concentration-time curve (AUC) is proportional to the extent of bioavailability for a drug.
TRUE
146
What can influence the duration of action and the effectiveness of the total dose of a drug?
Changes in the rate of absorption and extent of bioavailability
147
What is low bioavailability due to?
Incomplete absorption
148
What pumps the drug out of the gut wall cells back into the gut lumen?
A reverse transporter associated with P-glycoprotein.
149
What inhibits P-glycoprotein and gut wall metabolism?
Grapefruit juice
150
What is the enzyme system that can metabolize a drug in the gut wall?
CYP3A4
151
What determines whether drug products are pharmaceutical equivalent?
If they contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration.
152
What determines if two pharmaceutically equivalent drug products are bioequivalent?
When the rates and extents of bioavailability of the active ingredient in the two products are not significantly different under suitable test conditions.
153
How much of a drug that is absorbed from the rectum will bypass the liver?
50%
154
What part of the intestine is CYP3A4 present in?
The upper intestine
155
What does oral bioavailability depend on?
The individual drug structure; the presence of concurrent drugs or food in the GI tract; and the functional status of the digestive system/GI transit time.
156
T/F Gastrointestinal transit tends to be slower in women.
TRUE
157
T/F Men have a more acidic pH than women.
TRUE
158
What is a key determinant for predicting how well the drug will be absorbed?
The lipid solubility of the drug
159
T/F The more carbon atoms and the fewer oxygen atoms a drugl has, the more lipid-soluble the drug is.
TRUE
160
What type of drugs have slow absorption?
Those that are large in size or that possess bulky or oxygenated side chain groups.
161
Which type of drugs readily cross biologic membranes?
Un-ionized drugs
162
What is the degree of ionization?
The transfer of drug across a biologic barrier is proportional to the concentration gradient of the un-ionized form across the membrane.
163
What does the ratio of ionized versus unionized fraction of drug depend on?
The pKA of the drug and the pH of the surrounding tissues or fluids.
164
What does strongly acidic conditions in the stomach give rise to?
Ulceration/bleeding and gastroesophageal reflux disease (GERD)
165
What is the effect of antacids, histamine H2 receptor blockers, and proton pump inhibitors on the solubility of medications?
The gastric pH becomes more neutral and can decrease the solubility of some medications and reduce the rate and extent of absorption, and the extent of ionization.
166
What is necessary for oral drugs to be maximally absorbed?
Adequate residence time of the drug dose in the appropriate portion of the GI tract.
167
What is the rate and extent of perfusion of the gastrointestinal system influenced by?
The release of local factors (hormones) in the GI wall; and the application of exogenous agents (drugs).
168
What can significantly attenuate the availability of some drugs in the lumen of the GI tract?
The presence of foodstuffs.
169
What is the most ubiquitous method for drugs to pass across biological membranes?
Passive diffusion
170
What provides a barrier function to the passage of substrates and drugs across the placenta and the blood brain barrier?
Transporter proteins/ pumps
171
Where do CYPs play a vital role?
In intermediary metabolism
172
What is the role of CYPs?
They facilitate drug excretion by transforming the substrates into more water-soluble and polar molecules that can be eliminated in the urine and bile.
173
Where is the highest concentration of the CYP enzymes found?
The Liver
174
What is the role of CYP3A4 in the wall of the small intestine?
It plays a role to the efflux pumps in modulating drug access to the hepatic portal vein and ultimately to the systemic circulation; breaks down or inactivate drugs before they can have any pharmacologic effect in the body.
175
What is the activity of CYP3A modulated by?
Changes in expression, genetically determined limitations in function, substrate competiton.
176
What should be an integral part of the drug development process?
An assessment of the action of the microbiota
177
What does the total number of bacteria depend on?
The location within the length of the GI tract
178
T/F Metabolic capacity varies by location.
TRUE
179
What have microflora been shown to be capable of?
Conducting a large number of metabolic reactions.
