9. Biochemistry P163-171

Front 1

Lipoprotein functions

Back 1

p. 163

Front 2

Chylomicrons deliver dietary _____ to ________ and dietary ______ to ______.

Back 2

Triglycerides, peripheral tissues; Cholesterol, liver

Front 3

Which cells secrete chylomicrons?

Back 3

Intestinal epithelial cells

Front 4

Secretion is mediated by apolipoprotein _______.

Back 4

B-48

Front 5

True/False: VLDL delivers hepatic triglycerides to peripheral tissues.

Back 5

TRUE

Front 6

Where is VLDL secreted from?

Back 6

Liver

Front 7

LDL delivers hepatic cholesterol to _______.

Back 7

Peripheral tissues

Front 8

LDL is taken up by target cells via what process?

Back 8

Receptor-mediated endocytosis

Front 9

HDL mediates transport of cholesterol from where to where?

Back 9

Periphery to liver (reverse cholesterol transport)

Front 10

HDL acts as a repository for ______ and _______.

Back 10

apoC and apoE

Front 11

HDL is secreted from which 2 places?

Back 11

Liver and intestine

Front 12

Familial dyslipidemias

Back 12

p. 163

Front 13

Type I (hyperchylomicronemia) has elevated blood levels of ______.

Back 13

Triglycerides

Front 14

Type IIa (hypercholesterolemia) has increased levels of what?

Back 14

LDL

Front 15

What is the pathophysiology of type Iia?

Back 15

Decreased number of LDL receptors

Front 16

Type IIb (combined hyperlipidemia) has increased levels of ____ and _____.

Back 16

LDL, VLDL

Front 17

Type III (dysbetalipoproteinemia) has altered apolipoprotein __, and increased ____ and _____.

Back 17

E, IDL, VLDL

Front 18

Type IV (hypertriglyceridemia) is caused by hepatic overproduction of what?

Back 18

VLDL

Front 19

True/False: Type V (mixed hypertriglyericdemia) has only increased VLDL

Back 19

False; Increased VLDL and chylomicrons

Front 20

Metabolism sites

Back 20

p. 163

Front 21

Identify the site of metabolism (Mitochondria, Cytoplasm, or Both)

Front 22

Fatty acid oxidation (Beta-oxidation)

Back 22

Mitochondria

Front 23

Glycolysis

Back 23

Cytoplasm

Front 24

Gluconeogenesis

Back 24

Both

Front 25

Fatty acid synthesis

Back 25

Cytoplasm

Front 26

Urea cycle

Back 26

Both

Front 27

Acetyl-CoA production

Back 27

Mitochondria

Front 28

Heme synthesis

Back 28

Both

Front 29

HMP Shunt

Back 29

Cytoplasm

Front 30

Protein synthesis (RER)

Back 30

Cytoplasm

Front 31

Steroid synthesis (SER)

Back 31

Cytoplasm

Front 32

Aminolevulinate (ALA) synthesis

Back 32

p. 165

Front 33

ALA synthesis is the rate-limiting step for the produciton of what?

Back 33

Heme

Front 34

ALA is found in the ______

Back 34

Mitochondria

Front 35

Heme synthesis

Back 35

p. 165

Front 36

Heme synthesis occurs in the ______ and ________.

Back 36

Liver, bone marrow

Front 37

Underproduction of heme causes ___________ ___________ _________.

Back 37

Microcytic hypochromatic anemia

Front 38

Accumulation of intermediates causes what?

Back 38

Porphyria

Front 39

Porphyrias

Back 39

p. 165

Front 40

This type of porphyria is marked by a deficiency in uroporphyrinogen I synthetase

Back 40

Acute intermittent porphyria

Front 41

How does lead affect iron incorporation into heme?

Back 41

It prevents it

Front 42

This is the most common type of porphyria; a deficiency in uroporphynogen decarboxylase)

Back 42

Porphyria cutanea tarda

Front 43

Heme catabolism

Back 43

p. 165

Front 44

True/False: The progression of heme catabolism is heme --> biliverdin --> bilirubin

Back 44

TRUE

Front 45

Bilirubin is (Toxic/Non-toxic) to CNS and transported by _________.

Back 45

Toxic, albumin

Front 46

In the liver, heme is conjugated with __________.

Back 46

Glucoronate

Front 47

True/False: Urobilinogen is an intestinal intermediate that is never found in the blood and urine.

Back 47

False: a small amount is reabsorbed into blood and excreted in urine.

Front 48

Hemoglobin

Back 48

p. 165

Front 49

Hemoglobin is composed of many polypeptide subunits?

Back 49

4 (2 alpha, 2 beta)

Front 50

Carbon monoxide has a 200x (higher/lower) affinity for hemoglobin than does oxygen

Back 50

Higher

Front 51

T (taut) form of hemoglobin has a (high/low) affinity for oxygen

Back 51

Low

Front 52

R (relaxed) form of hemoglobin has a (high/low) affinity for oxygen

Back 52

High

Front 53

True/False: Myoglobin, like hemoglobin, has a sigmoid-shaped O2 binding curve.

Back 53

FALSE

Front 54

Hemoglobin structure regulation

Back 54

p. 165

Front 55

Increased Cl, H, CO2, DPG, and temperature favor shift over curve to (left/right).

Back 55

Right (unloads more O2)

Front 56

True/False: Shift to right is due to preference for T form over R form.

Back 56

TRUE

Front 57

Methemoglobinemia

Back 57

p. 165

Front 58

True/False: Methemoglobin is an oxidized form of hemoglobin that binds O2 more readily.

Back 58

False: it binds O2 less readily

Front 59

CO2 transport in blood

Front 60

CO2 binds to (heme/amino acids in globin chain).

Back 60

Amino acids in globin chain

Front 61

CO2 binding favors which form of hemoglobin? And what sort of shift does it cause?

Back 61

T. Right shift.

Front 62

Vitamins: fat soluble

Back 62

p. 166

Front 63

What are the fat soluble vitamins?

Back 63

A,D,E,K

Front 64

The absorption of fat soluble vitamins depends on what two organs?

Back 64

small intestine (ileum) and pancreas

Front 65

Is toxicity more common for fat or water soluble vitamins?

Back 65

fat soluble becauase the vitamins accumulate in the fat

Front 66

What can cause fat-soluble vitamin deficiencies besides just general lack of intake?

Back 66

malabsorption syndromes and mineral oil intake

Front 67

Vitamins: water soluble

Back 67

p. 166

Front 68

What are the water soluble vitamins?

Back 68

B1, 2, 3, 5, 6, 12, C, Biotin, Folate

Front 69

What do B complex deficiencies cause?

Back 69

dermatitis, glossitis, and diarrhea

Front 70

Vitamin A (retinol)

Back 70

p. 166

Front 71

What is the function of vitamin A?

Back 71

constituent of visual pigments

Front 72

Match up the appropriate vitamin with these alternates names? A.thiamine, B.riboflavin, C.niacin, D.retinol,

Back 72

C2

Front 73

What does a deficiency of vitamin A cause?

Back 73

night blindness and dry skin

Front 74

Vitamin B1 (thiamine)

Back 74

p. 166

Front 75

What does a deficiency of vitamin B1 cause?

Back 75

Ber1Ber1 and Wernicke-Korsakoff syndrome

Front 76

What is the function of vitamin B1?

Back 76

Cofactor for oxidative decarboxylation of alpha-keto acids and a transketolase in the HMP shunt.

Front 77

Beriberi is characterized by what 3 symptoms?

Back 77

polyneuritis, cardiac pathology, and edema

Front 78

Vitamin B2 (riboflavin)

Back 78

p. 167

Front 79

What does a deficiency of vitamin B2 cause?

Back 79

angular stomatitis, cheilosis, corneal vascularization

Front 80

What is the function of vitamin B2?

Back 80

cofactor in oxidation and reduction

Front 81

Vitamin B3 (niacin)

Back 81

p. 167

Front 82

What is vitamin B3 a constituent of?

Back 82

NAD+, NADP+

Front 83

What does a deficiency of vitamin B3 cause?

Back 83

Pellagra

Front 84

What are the symptoms of pellagra?

Back 84

Diarrhea, Dermatitis, Dementia

Front 85

Vitamin B5 (pantothenate)

Back 85

p. 167

Front 86

What is vitamin B5 a constituent of?

Back 86

CoA

Front 87

A deficiency in vitamin B5 causes what 4 problems?

Back 87

dermatitis, enteritis, alopecia, adrenal insufficiency

Front 88

Vitamin B6 (pyridoxine)

Back 88

p. 167

Front 89

When vitamin B6 is converted to ___, it is a cofactor in what three processes?

Back 89

pyridoxal phosphate; cofactor in transamination, decarboxylation, and trans-sulfuration

Front 90

What may induce a deficiency in vitamin B6?

Back 90

INH and oral contraceptives

Front 91

Biotin

Back 91

p. 167

Front 92

Biotin is a cofactor in which 3 carboxylations?

Back 92

pyruvate to oxaloacetate, acetyl-CoA to malonyl CoA, and proprionyl-CoA to methylmalonylCoA

Front 93

The use of __ and ingestion of __ cause a deficiency in biotin?

Back 93

antibiotics; raw eggs

Front 94

Folic acid

Back 94

p. 167

Front 95

What is the most common vitamin deficiency in the US?

Back 95

folic acid

Front 96

Neurologic symptoms with anemia are seen in folic acid or B12 deficiency?

Back 96

B12

Front 97

What is folic acid important in the synthesis of?

Back 97

Nitrogenous bases in DNA and RNA

Front 98

What two drugs are PABA analogues (the precursor of folic acid in bacteria)?

Back 98

sulfa drugs and dapsone

Front 99

Vitamin B12 (cobalamin)

Back 99

p. 168

Front 100

Vitamin B12 is involved in which two conversions?

Back 100

Homocysteine to Methionine and Metholmalonyl CoA to SuccinylCoA

Front 101

Where is vitamin B12 stored

Back 101

liver

Front 102

What are the 3 main causes of vitamin B12 defiiciency?

Back 102

malabsorption, lack of intrinsic factor, and absence of terminal ileum

Front 103

What test is used to determine a deficiency of vitamin B12

Back 103

Schilling

Front 104

Vitamin C (ascorbic acid)

Back 104

p. 169

Front 105

Deficiency of Vit C causes what?

Back 105

Scurvy

Front 106

Vit C is necessary for ________ of proline and lysine in ________ synthesis

Back 106

hydroxylation / collagen

Front 107

Vit C also facilitates absorption of what?

Back 107

Iron - by keeping iron in Fe2+ reduced state

Front 108

Vit C is necessary as a cofactor for what?

Back 108

Dopamine --> NE

Front 109

What are the clinical findings of scurvy?

Back 109

Swollen Gums, bruising, anemia, poor wound healing

Front 110

Vitamin D

Back 110

p. 169

Front 111

D2, also called _______ is consumed from what?

Back 111

ergocalciferol, comsumed in milk

Front 112

Cholecalciferol, also called ____ is formed where?

Back 112

D3, formed in sun-exposed skin

Front 113

25-OH D3 is what form of Vit D

Back 113

Storage form

Front 114

1,25 (OH)2D3 is what form of Vit D

Back 114

Active form

Front 115

Deficiency of Vit D in children causes? In adults?

Back 115

Children - Rickets // Adults - Osteomalacia. Also can cause hypocalcemic tetany

Front 116

Vit D functions to

Back 116

Increase intestinal absorption of calcium and phosphate

Front 117

Too Much Vitamin D has three clinical effects. What are they?

Back 117

Hypercalcemia, loss of appetite, stupor.

Front 118

The 6 causes of hypercalcemia are:

Back 118

Vit D. Intoxication / Malignancy / Hyperparathyroidism / Milk-Alkali syndrome / Sarcoidosis / Paget's disease of bone

Front 119

Excess Vit D is seen in what disease state?

Back 119

Sarcoidosis - where epithelial macrophages convert vit D into its active form

Front 120

Vitamin E

Back 120

p. 169

Front 121

Deficiency in Vit E causes?

Back 121

Increased fragility of erythrocytes (E is for erythrocytes)

Front 122

Vit E functions as an ______ to protect _______

Back 122

Antioxidant, to protect erythrocytes from hemolysis

Front 123

Vitamin K

Back 123

p. 169

Front 124

T/F - Vitamin K deficiency causes neonatal thrombi and pulmonary emboli.

Back 124

False - Vit K deficiency causes - neonatal hemorrhage

Front 125

How does Vit K effect the PT, aPTT and Bleeding time?

Back 125

Increased PT and aPTT but normal bleeding time.

Front 126

What coagulation factors require Vitamin K?

Back 126

Factors II, VII, IX, X and protein C and S. (remember 1972).

Front 127

How does warfarin work?

Back 127

It is a vitamin K antagonist.

Front 128

What does Vit K catalyze?

Back 128

The gamma-carboxylation of glutamic acid residues on various proteins concerned with blood clotting.

Front 129

Where is Vit K synthesized?

Back 129

Vit K is synthesized by the normal intestinal flora.

Front 130

Ethanol Metabolism

Back 130

p. 169

Front 131

What are the two enzymes required to convert Ethanol --> acetaldehyde --> acetate?

Back 131

Alcohol dehydrogenase for the first reaction, and acetaldehyde dehydrogenase for the second.

Front 132

What is the limiting reagent in the above reaction?

Back 132

NAD+ is the limiting reagent for both reactions

Front 133

How does Disulfiram work?

Back 133

Disulfiram (antabuse) - inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms)

Front 134

When I go out drinking with the class of 2006, why is PBL so painful the next morning?

Back 134

Because acetaldehyde accumulates in my system, and after 2 years, PBL is always painful.

Front 135

Ethanol Hypoglycemia

Back 135

p. 170

Front 136

How does ethanol metabolism lead to hypoglycemia?

Back 136

Ethanol metabolism increases NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate, thereby inhibiting gluconeogenesis and leading to hypoglycemia.

Front 137

What is hepatocellular steatosis, and how does it occur?

Back 137

Hepatocellular steatosis = hepatic fatty change… It occurs because of the above pathway resulting in an increase in NADH/NAD+ ratio, which causes a shunting away from glycolysis and toward fatty acid synthesis.

Front 138

Kwashiorkor vs. marasmus

Back 138

p. 170

Front 139

What is kwashiorkor?

Back 139

Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change).

Front 140

What is marasmus?

Back 140

protein - calorie malnutrition resulting in tissue wasting.

Front 141

The clinical picture of a small child with a swollen belly is characteristic of kwashiorkor or marasmus?

Back 141

Kwashiorkor

Front 142

Kawashiorkor results from a protein-deficient M.E.A.L. What does M.E.A.L. stand for?

Back 142

Malabsorption, Edema, Anemia, Liver (fatty)

Front 143

Summary of pathways

Back 143

p.171

Front 144

Glucose is first converted to what in the cell?

Back 144

Glucose-6-phosphate

Front 145

What are the three products that glucose-6-phosphate is converted to in the cell?

Back 145

Glucose-1-P (to glycogen pathway) // Fructose-6-P (To TCA) // 6-phosphogluconolactone (to Ribose-5 phosphate pathway)

Front 146

What are the steps of the TCA?

Back 146

Acetyl-CoA --> Citrate --> Isocitrate --> alpha-ketoglutarate --> Succinyl-CoA --> Succinate --> Fumarate --> Malate --> Oxaloacetate

Front 147

What are the steps of the Urea Cycle?

Back 147

Aspartate --> Arginosuccinate --> Arginine --> Ornithine --> Citrulline --> Arginosuccinate

Front 148

Odd chain fatty acids enter the TCA through what series of molecules?

Back 148

Odd chain FA --> Propionyl-CoA --> Methylmalonyl-CoA --> Succinyl-CoA… into TCA

Front 149

Acetyl Co-A, aside from entering the TCA, can be converted into what three molecules?

Back 149

Mevalonic acid, Acetoacetyl-CoA, malonyl-CoA

Front 150

Beta - hydroxybutyrate is formed from Acetyl-CoA through what precursors?

Back 150

Acetyl-CoA --> Acetoacetyl-CoA --> Acetoacetate --> Beta-hydroxybutyrate

Front 151

Cholesterol is formed from acetyl co-A through what precursors?

Back 151

Acetyl-CoA --> Mevalonic Acid --> Isoprene --> Squalene --> Lanosterol --> Cholesterol

Front 152

The conversion of Arginine to Ornithine creates as a byproduct, what?

Back 152

H20 --> Urea

Front 153

NH4 + CO2, leads to _______, and enters the Urea cycle where?

Back 153

Leads to Carbamoyl Phosphate, enters at the conversion of ornithine --> citrulline

Front 154

Write the steps of conversion of glucose to acetyl-CoA

Back 154

Glucose --> Glucose -6-P --> Fructose-6-P --> fructose-1,6-bisphosphate --> glyceraldehyde-3P --> 1,3-bis-phosphoglycerate --> 3-phosphoglycerate --> 2-phosphoglycerate --> phosphoenolpyruvate --> pyruvate --> acetyl-coA