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MBOD block 4 Flashcards

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2
Q

What is metabolism?

A

The sum of all of the chemical reactions that can occur in a living organism.

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3
Q

What is the function of metabolism?

A

To supply all of the needs of every cell.

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4
Q

What are examples of anabolic pathways?

A

Biosynthetic pathways; Detoxification and waste disposal pathways.

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5
Q

What are examples of catabolic pathways?

A

Fuel storage pathways; Fuel oxidative pathways

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6
Q

What are some of the products of anabolic pathways?

A

Uric Acid, Urea, waste products

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7
Q

What are some of the products of catabolic pathways?

A

Energy, CO2, H20, ATP

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8
Q

What are some dietary fuels?

A

Carbohydrate, Fat, Protein

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9
Q

What are the categories of Metabolic pathways?

A

Anabolic (biosynthetic); Catabolic (degradative); ATP-synthesizing pathways.

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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

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11
Q

What things occur during the transformation of ATP to ADP in the ATP-ADP cycle?

A

Motion, Active transport, biosyntheses, signal amplification

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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

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13
Q

The breakdown of ATP to AMP produces what products?

A

Pyrophosphate -> 2Pi

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14
Q

What are carbohydrates, fats, and proteins oxidized to?

A

CO2, H2O, energy, (urea-proteins)

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15
Q

Which compound has the highest standard free energy?

A

Phosphate Enol pyruvate

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16
Q

What is an example of enol phosphate bond?

A

Phosphoenolpyruvate

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17
Q

What is an example of an anhydride bonded to carbon?

A

1,3-bisphosphoglycerate

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18
Q

What is creatine phosphate?

A

An activated carrier that stores energy in muscle.

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19
Q

What is an example of an anhydride bonded to phosphate?

A

ATP

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20
Q

Which compound has a phosphoester bond?

A

Glucose 6-phosphate

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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.

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22
Q

What is a metabolic pathway?

A

A series of reactions leading from the transformation of one metabolite to another.

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23
Q

What is an enzyme catalyzed reaction?

A

The product of one enzyme becomes the substrate for the next enzyme.

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24
Q

T/F All pathways are linked and regulated.

A

TRUE

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25
Q

T/F Pathways are irreversible.

A

TRUE

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26
Q

How many irreversible steps are there in every pathway?

A

At least one

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27
Q

What is the slowest step in a pathway?

A

The rate limiting step

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28
Q

What is the committed step?

A

The first irreversible step unique to a pathway.

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29
Q

What are the tupes of metabolic pathways?

A

Linear, branched, cyclic, cascade/amplification

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30
Q

What are the characteristics of a linear pathway?

A

One substrate, one product

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31
Q

What is the characteristic of a branched pathway?

A

Multiple products

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32
Q

What are the characteristics of a cyclic pathway?

A

Pathway starts and ends with the same compound; molecules enter and leave the cycle.

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33
Q

What are some examples of a cascade or amplification pathway?

A

Signal transduction, blood clotting

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34
Q

How do you control the pathways?

A

By regulating the activity of enzymes or the amount of an enzyme.

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35
Q

What are types of regulation or control of enzymes and metabolic pathways?

A

Allosteric control; feedback inhibition; reversible covalent modification

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36
Q

What is required for metabolic pathways?

A

Cofactors (NADH, FADH2, THF, Vit.D,C,K,A

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37
Q

T/F Each tissue has its own unique metabolism.

A

TRUE

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38
Q

What is glucose 6-phosphate a precursor to?

A

Nucleotides

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39
Q

What is fructose 6-phosphate a precursor to?

A

Amino sugars, glycolipids, glycoproteins

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40
Q

What is dihydroxyacetone phosphate a precursor to?

A

Lipids

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41
Q

What is 3-phosphoglycerate a precursor to?

A

Serine

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42
Q

What is pyruvate a precursor to?

A

Alanine

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43
Q

What is citrate a precursor to?

A

Cholesterol, fatty acids

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44
Q

What is oxaloacetate a precursor to?

A

Aspartate, amino acids, purines, pyrimidines

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45
Q

What is a-ketoglutarate a precursor to?

A

Glutamate, amino acides, purines

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46
Q

What is succinyl CoA a precursor to?

A

Heme chlorophyll

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47
Q

What is the first stage of Metabolism?

A

Breakdown of macromolecules to monomers.

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48
Q

What is the 2nd stage of Metabolism?

A

Breakdown of simple subunits to Acetyl CoA accompanied by production of limited amounts of ATP and NADH

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49
Q

What is the 3rd stage of Metabolism?

A

Complete oxidation of Acetyl CoA to H2O and CO2 accompanied by production of large amounts of ATP in the mitochondrion

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51
Q

What are the functions of carbohydrates?

A

Nutritional roles; source of energy; energy storage; vitamins; non-nutritive dietary role; structural component; molecular recognition

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52
Q

What is the major dietary carbohydrate?

A

Starch; followed by disaccharides

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53
Q

What is the source of energy that can be used by all tissues?

A

Glucose

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54
Q

What do mammals stroe glucose as?

A

Glycogen

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55
Q

Which vitamin is a carbohydrate?

A

Vitamin C

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56
Q

What is a nondigestible carbohydrate and what is its role?

A

Fiber; important in normal digestion

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57
Q

What are carbohydrates a structural component of?

A

cofactors; DNA/RNA; glysoproteins; glycolipids; proteoglycans; bacterial cell wall; cellulose

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58
Q

How are carbohydrates involved in molecular recognition?

A

Receptors; adhesion molecules; cell surface markers; soluble and membrane glycoproteins; glycolipids

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59
Q

What is the blood glucose concentration a balance of?

A

Pathways that use blood glucose and those that add glucose back to the blood.

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60
Q

Which hormones play a major role in controlling blood glucose conc.?

A

Insulin and glucagon

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61
Q

What is the normal blood glucose concentration?

A

100mg/dL

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62
Q

What happens to the insulin/glucagon ratio after a high carbohydrate meal?

A

The ratio increases.

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63
Q

What does the balance of metaboiic homeostasis depend on?

A

Fuel availability and Tissue needs

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64
Q

What are the 3 signals used to maintain metabolic homeostasis?

A

Blood level of nutrient; hormone level; nerve impulse

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65
Q

What are the pathways and reactions that increase blood glucose?

A

Digestion of dietary carbs; conversion of other dietary sugars to glc; glycogenolysis; gluconeogenesis

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66
Q

What are the pathways that use blood glucose?

A

Glucose transporters and phosphorylation; glycolysis; glycogenesis; phosphogluconate pathway; sorbitol pathway (aldose reductase).

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67
Q

What is the key glucoregulatory hormone?

A

Insulin

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68
Q

What is insulin?

A

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

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69
Q

What does insulin do?

A

Stimulates glucose storage and uptake my muscle and adipose tissue; increases hepatic glycogenesis and lipogenesis.

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70
Q

What are the counter-regulatory hormones?

A

Glucagon; epinephrine; cortisol; growth horm.

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71
Q

What does glucagon do?

A

Increases blood glucose by stimulating glycogenolysis and gluconeogenesis.

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72
Q

Where is glucagon synthesized?

A

By the alpha cells of the pancreas.

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73
Q

What enhances the secretion of glucagon?

A

Hypoglycemia

74
Q

What does epinephrine do?

A

Stimulates glycogenolysis and adipose tissue lipolysis. Inhibits insulin secretion.

75
Q

What is epinephrine secreted in response to?

A

Stress

76
Q

What is secretion of epinephrine enhanced by?

A

Hypoglycemia

77
Q

What does cortisol do?

A

Stimulates glucagon release; stimulates gluconeogenesis

78
Q

When is growth hormone secreted?

A

In hypoglycemia

79
Q

What does growth hormone do?

A

Increases hepatic glucose production and reduces glucose use by some tissues.

80
Q

What are disorders of blood glucose?

A

Hypoglycemia; Diabetes; Hyperglycemia

81
Q

What is hypoglycemia?

A

Low blood sugar.

82
Q

What is hypoglycemia caused by?

A

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
Q

What does the metabolism of alcohol do?

A

Increases NADH in the liver, which inhibits gluconeogenesis. Disrupts the NADH/NAD+ ratio, which affects reactions.

84
Q

What is the normal of glucose concentration?

A

70-100 mg/dL

85
Q

What is mild hypoglycemia?

A

BG less than 68mg; results in decreased glc uptake by the brain. Symptoms include feeling shaky, nervous, hungry, sweaty.

86
Q

What is mild to moderate hypoglycemia?

A

Blood glucose less than 49mg%; results in cognitive dysfunction. Symptoms include headache, mood change, confusion, rapid heart beat.

87
Q

What is severe hypoglycemia?

A

Usually requires assistance; may lose consciousness and require an injection of glucagon or dextrose.

88
Q

What is Type 1 diabetes?

A

A deficiency of insulin

89
Q

What is Type 2 diabetes?

A

Decreased secretion of insulin or reduced ability to respond to insulin.

90
Q

What does the exposure of red blood cells to hyperglycemia result in?

A

Nonenzymatic glycosylation of hemoglobin forming hemoglobin A1c.

91
Q

What is imparied glucose tolerance?

A

An asymptomatic condition that is diagnosed on the basis of an OGTT, the blood glucose values being intermediate between normal and diabetic.

92
Q

What are ways used to measure glucose?

A

Blood glucose assays; reduction methods; glucose oxidase assay; hexokinase assay; urine glucose assays; glucose oxidase dipsticks

93
Q

How does a glucose oxidase assay work?

A

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
Q

How does a hexokinase assay work?

A

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
Q

What is glycosuria?

A

The presence of significant quantities of glucose in urine; blood glucose >160-180 mg/dL; decreased renal tubular reabsorption.

96
Q

What are dipsticks?

A

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
Q

What are the characteristics of the epithelium?

A

Polarized, tight junctions, apical membrane, basolateral membrane.

99
Q

What do the epithelial cells control the passage of?

A

Substances between the intestinal lumen and the milieu interieur

100
Q

What is able to pass through tight junctions?

A

Only very small molecules.

101
Q

T/F The distal epithelium is tighter than the proximal epithelium.

A

TRUE

102
Q

What are the control mechanisms for absorption?

A

The intracellular transport pathways.

103
Q

What creates the osmotic gradient that facilitates the movement of water into the lumen?

A

The digestion of ingested food.

104
Q

What do active mechanisms involve?

A

The secretion of electrolytes into the lumen

105
Q

How does the excess Cl- move out of the cell into the intestinal lumen?

A

Through the Cysic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl-channel.

106
Q

What does the movement of excess Cl through the channel do?

A

Puts an osmotically active ion in the lumen; creates a greater negative charge in the lumen relative to the interstitium.

107
Q

What does the negative charge in the lumen do?

A

It attracts another osmotically active ion, Na+ to move through the tight junctions.

108
Q

What attracts water to move through the tight junctions?

A

The increase in osmotically active molecules in the lumen

109
Q

What are the ways in which sodium moves into the epithelial cells?

A

Leakiness/Na-channels; cotransport with another molecule

110
Q

What prevents an electrically depolarizing accumulation of Na+ in the epithelial cell?

A

NA+-K+ATPase on the basolateral membrane pumps the Na+ from the cell.

111
Q

How does water move?

A

Paracellularly by passive diffusion; and facilitated transport through active and regulated water channels-aquaporins (AQP1, AQP3, AQP4)

112
Q

Which carrier transports one molecule of sugar with two Na+?

A

Solute carrier family 5 member 1 (SLC5A1)

113
Q

What does the sugar diffuse down its concentration gradient through?

A

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
Q

What does fructose use to move from the lumen into the epithelial cell?

A

Solute carrier family 2 member 5 (SLC2A5) and SLC2A2

115
Q

How are the ingested proteins broken down?

A

By the action of secreted peptidases, resulting in amino acids, di-, and tri-peptides.

116
Q

How are di - and tri- peptides transported?

A

In a H+ dependent cotransport mechanism by the peptide transporter coded for by the solute carrier family 15 member 1 gene (SLC15A1)

117
Q

What does emulsification do?

A

Disperse triglycerides and makes them more accessible for hydrolysis to monoglycerides.

118
Q

What is the structure of micelles?

A

A hydrophobic interior with the hydrophilic carboxylates and glycerol backbones facing the hydrophilic environment.

119
Q

How are fatty acids transported?

A

By binding ot the Fatty Acid Binding Protein (FABP2); and by the Fatty Acid Transport Protein 4 (SLC27A4 gene product)

120
Q

How is Iron, in its ferric form, converted to the ferrous form in the duodenum?

A

By the action of ferroreductase.

121
Q

What is iron transported into the epithelial cell by?

A

The protein coded by the solute carrier family 11 member 2 gene SLC11A2/NRAM2/DMT1

122
Q

What does the SLC11A2 protein-mediated transport require?

A

An acidic environment.

123
Q

What acts as an iron store in periods of abundance?

A

Ferritin

124
Q

During periods of limited iron availability, there is increased synthesis of what two proteins?

A

SLC40A1/ferroportin; and TF

125
Q

What is the role of SLC40A1?

A

Transports iron out of the epithelial cell.

126
Q

What is the role of TF?

A

Binds the iron to transport it in the blood.

127
Q

How does Ca enter the duodenal epithelial cells when it is not abundant?

A

In an electrochemically favorable direction through TRPV5 and TRPV6 Ca channels

128
Q

What removes the Ca that enters the cells on the basolateral membrane?

A

Ca2+-ATPase and Na+-Ca2+ exchange, SLC8A1; secondary active transport mechanism

129
Q

T/F Phosphate absorption is similarly both passive and active.

A

TRUE

130
Q

How does the passive absorption of phosphate occur?

A

It is paracellular.

131
Q

How does the active absorption of phosphate occur?

A

Through Na+-H2PO4- cotransport; SLC34A2

133
Q

What areas do the portal system drain?

A

The distal end of the esophagus, stomach, small and large intestines, proximal portion of the rectum, pancreas, and spleen.

134
Q

T/F The liver receives both nutrient-rich deoxygenated blood (portal vein) and oxygenated blood (hepatic arteries).

A

TRUE

135
Q

What is the role of hepatocytes?

A

Detoxifies the blood, metabolizes fats, carbohydrates, and drugs, and produce bile.

136
Q

What receives the deoxygenated and oxygenated blood?

A

The sinusoids

137
Q

How does the blood exit the sinusoids?

A

Into a central vein, into the IVC

138
Q

Why is the concentration of oral drugs reduced before entering the systemic circulation?

A

Because of hepatic metabolism; First-pass effect

139
Q

How is the proximal portion of the rectum drained?

A

Via the superior rectal vein -> inferior mesenteric vein

140
Q

How is the remainder of the rectum drained by?

A

The middle rectal vein; inferior rectal vein

141
Q

What are the routes of drug administration?

A

Intravenous; Subcutaneous; Intramuscular; Oral Ingestion

142
Q

What is the most common, safest, convenient, and economical method of drug administration?

A

Oral ingestion

143
Q

What are some disadvantages to the oral route?

A

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
Q

What is bioavailability?

A

The fraction of unchanged drug reaching the systemic circulation following administration by any route

145
Q

T/F The area under the blood concentration-time curve (AUC) is proportional to the extent of bioavailability for a drug.

A

TRUE

146
Q

What can influence the duration of action and the effectiveness of the total dose of a drug?

A

Changes in the rate of absorption and extent of bioavailability

147
Q

What is low bioavailability due to?

A

Incomplete absorption

148
Q

What pumps the drug out of the gut wall cells back into the gut lumen?

A

A reverse transporter associated with P-glycoprotein.

149
Q

What inhibits P-glycoprotein and gut wall metabolism?

A

Grapefruit juice

150
Q

What is the enzyme system that can metabolize a drug in the gut wall?

A

CYP3A4

151
Q

What determines whether drug products are pharmaceutical equivalent?

A

If they contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration.

152
Q

What determines if two pharmaceutically equivalent drug products are bioequivalent?

A

When the rates and extents of bioavailability of the active ingredient in the two products are not significantly different under suitable test conditions.

153
Q

How much of a drug that is absorbed from the rectum will bypass the liver?

A

50%

154
Q

What part of the intestine is CYP3A4 present in?

A

The upper intestine

155
Q

What does oral bioavailability depend on?

A

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
Q

T/F Gastrointestinal transit tends to be slower in women.

A

TRUE

157
Q

T/F Men have a more acidic pH than women.

A

TRUE

158
Q

What is a key determinant for predicting how well the drug will be absorbed?

A

The lipid solubility of the drug

159
Q

T/F The more carbon atoms and the fewer oxygen atoms a drugl has, the more lipid-soluble the drug is.

A

TRUE

160
Q

What type of drugs have slow absorption?

A

Those that are large in size or that possess bulky or oxygenated side chain groups.

161
Q

Which type of drugs readily cross biologic membranes?

A

Un-ionized drugs

162
Q

What is the degree of ionization?

A

The transfer of drug across a biologic barrier is proportional to the concentration gradient of the un-ionized form across the membrane.

163
Q

What does the ratio of ionized versus unionized fraction of drug depend on?

A

The pKA of the drug and the pH of the surrounding tissues or fluids.

164
Q

What does strongly acidic conditions in the stomach give rise to?

A

Ulceration/bleeding and gastroesophageal reflux disease (GERD)

165
Q

What is the effect of antacids, histamine H2 receptor blockers, and proton pump inhibitors on the solubility of medications?

A

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
Q

What is necessary for oral drugs to be maximally absorbed?

A

Adequate residence time of the drug dose in the appropriate portion of the GI tract.

167
Q

What is the rate and extent of perfusion of the gastrointestinal system influenced by?

A

The release of local factors (hormones) in the GI wall; and the application of exogenous agents (drugs).

168
Q

What can significantly attenuate the availability of some drugs in the lumen of the GI tract?

A

The presence of foodstuffs.

169
Q

What is the most ubiquitous method for drugs to pass across biological membranes?

A

Passive diffusion

170
Q

What provides a barrier function to the passage of substrates and drugs across the placenta and the blood brain barrier?

A

Transporter proteins/ pumps

171
Q

Where do CYPs play a vital role?

A

In intermediary metabolism

172
Q

What is the role of CYPs?

A

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
Q

Where is the highest concentration of the CYP enzymes found?

A

The Liver

174
Q

What is the role of CYP3A4 in the wall of the small intestine?

A

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
Q

What is the activity of CYP3A modulated by?

A

Changes in expression, genetically determined limitations in function, substrate competiton.

176
Q

What should be an integral part of the drug development process?

A

An assessment of the action of the microbiota

177
Q

What does the total number of bacteria depend on?

A

The location within the length of the GI tract

178
Q

T/F Metabolic capacity varies by location.

A

TRUE

179
Q

What have microflora been shown to be capable of?

A

Conducting a large number of metabolic reactions.

MBOD Block 4 (5 decks)

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