Dems Exam 2 (Carbohydrate Metabolism)

Front 1

What catalyzes the rate limiting step of the glycolytic pathway?

Back 1

Phosphofructokinase (Fructose 6 phosphate -> Fructose 1,6-bisphosphate); Rxn also uses ATP

Front 2

Does vigorously exercising muscle have an increased or decreased conversion of pyruvate to lactate?

Back 2

Increased

Front 3

Low hemoglobin and low lactate levels could be associated with a deficiency of which enzyme?

Back 3

Pyruvate kinase

Front 4

A low NAD+/NADH ratio would increase or decrease the oxidation of acetyl CoA by the TCA cycle?

Back 4

Decrease. Low ATP/ADP or GTP/GDP would stimulate.

Front 5

What is biotin required for?

Back 5

The synthesis of glucose from pyruvate (specifically, it is a coenzyme for the conversion of pyruvate to OAA, with pyruvate carboxylase)

Front 6

Where does gluconeogenesis occur?

Back 6

Liver and Kidney

Front 7

When does gluconeogenesis occur?

Back 7

Overnight for maintaining blood glucose

Front 8

What rxns are unique to gluconeogenesis?

Back 8

OAA -> PEP (PEP carboxylase), Fructose 1,6-bisphosphate -> fructose 6-phosphate (fructose 1,6-bisphosphotase), glucose 6 phospahte -> glucose (glucose 6 phosphotase)

Front 9

What are the two main ways that gluconeogenesis is regulated?

Back 9

Glucagon and the availability of substrates.

Front 10

Which amount is higher, the Estimated Average Requirement (EAR) or the Recommended Dietary Allowance (RDA)?

Back 10

RDA

Front 11

What are the BMI cutoffs?

Back 11

Underweight <19
Acceptable 19-26
Overweight 26.1-29
Obese 30-40
Morbid Obesity >40

Front 12

What questions should you ask when using the WAVE dietary assessment?

Back 12

Weight, Activity, Variety, Excess

Front 13

Approximately what percentages of Resting energy expenditure, Thermic Efect of Food and Energy Expended in Physical Activity make up the daily expenditure of an average person?

Back 13

8% - TEF
60-75% - EEPA
17-32% - REE

Front 14

By how much do patients underreport food intake?

Back 14

20-40%

Front 15

In what order do we burn foods?

Back 15

Protein, Carbs, Fat

Front 16

What are anabolic vs. catabolic pathways?

Back 16

Anabolic pathways occur when the body is in positive energy balance. Building polymers from monomers. Catabolic pathways occur during the phase of nutrient breakdown in order to meet the energy needs of the body.

Front 17

What constitutes a key step?

Back 17

Changing location, investing energy (adding phosphate group), using energy, rate limiting step

Front 18

What is invested in the Energy Investment phase of glycolysis?

Back 18

2 ATP

Front 19

What is gained in the Energy Payoff Phase of glycolysis?

Back 19

4 ATP, 2NADH

Front 20

Glucose -> Glucose 6-phosphate: enzyme? importance?

Back 20

Hexokinase or glucokinase; important because it is irreversible (traps glucose inside cell) and invests 1 ATP

Front 21

What is the difference between Hexokinase and Glucokinase?

Back 21

Hexokinase - present in all cells, useful at low glucose [ ], low Vmax
Glucokinase - present in liver and pancreatic beta cells (regulates insulin release), higher [ ] and high Vmax **inhibited by fructose 6-phosphate

Front 22

Fructose-6-phosphate -> Fructose 1,6-bisphosphate: enzyme? importance

Back 22

Phosphofructokinase 1 (PFK 1), rate limiting and committed step

Front 23

What controls PFK 1?

Back 23

Most potent activator of PFK 1 = Fructose 2,6-bisphosphate. Inhibited by ATP/citrate. stimulated by AMP

Front 24

How do we get F 2,6-bisphosphate?

Back 24

Fructose 6-phosphate -> Fructose 2,6-bisphosphate
enzyme: PFK 2

Front 25

PFK 2 is bifunctional. What does what?

Back 25

Kinase favors F 2,6 BP. Phosphotase favors F 6-phosphate.

Front 26

Does F6P -> F 1,6 BP require energy?

Back 26

Yes. ATP > ADP

Front 27

2 Glyceraldehyde-3-phosphate -> 2 1,3-bisphosphoglygerate: energetics of rxn? enzyme?

Back 27

Gain of 2 NADH (beginning of energy payoff phase), glyceraldehyde-3-phosphate dehydrogenase

Front 28

1,3, bisphosphoglycerate -> 3 phosphoglycerate: energetics? enzyme?

Back 28

ATP gained; first substrate level phosphorylation. phosphoglycerate kinase.

Front 29

phosphoenol pyruvate -> pyruvate: energetics? enzyme?

Back 29

Gain 1 ATP; 2nd substrate level phosphorylation. pyruvate kinase. Irreversible

Front 30

In the presence of O2, what is pyruvate oxidized to?

Back 30

Acetyl CoA

Front 31

What happens to the lactate formed in exercising muscle?

Back 31

It travels to the liver where it is converted to glucose via glucogneogenesis.

Front 32

What does the pentose phosphate pathway produce from glucose 6-phosphate?

Back 32

NADPH, ribose 5-phosphate, glycolytic intermediates

Front 33

What catalyzes the first, committing and rate limiting step of the pentose phosphate pathway?

Back 33

Glucose-6-phosphate dehydrogenase

Front 34

Where is the pyruvate dehydrogenase complex?

Back 34

mitochondrial matrix

Front 35

What is the clinical consequence of a thiamine deficiency?

Back 35

Thiamine is required for the oxidation of pyruvate to Acetyl CoA. Neurologic deficiency.

Front 36

What inhibits/activates the pyruvate dehydrogenase complex(PDH)?

Back 36

Inhibited by ATP, Acetyl CoA, NADH, and fatty acids. Activated by AMP, NAD+.

Front 37

In the fasting state, PDH is inhibited, promoting what pathway?

Back 37

gluconeogenesis

Front 38

PDH is active or inactive in the phosphorylated state?

Back 38

inactive

Front 39

What inhibits the kinase that phosphorylates (and inactivates)PDH?

Back 39

ADP. ADP thus activates PDH and ATP inactivates PDH. Calcium stimulates the phosphatase, so it also activates PDH.

Front 40

Where do the rxns of the TCA cycle take place?

Back 40

mitochondria

Front 41

What is the source of the Carbons for CO2 and the electrons of NADH and FADH2 in the TCA cycle?

Back 41

Acetyl CoA

Front 42

The condensation between acetyl CoA and oxaloacetate yields what? Why is this step important?

Back 42

It yields citrate. It is important because it is irreversible.

Front 43

What enzyme is used in the following rxn: pyruvate > Acetyl CoA?

Back 43

pyruvate dehydrogenase

Front 44

Where does oxidative phosphorylation take place?

Back 44

The electron transport chain consists of four multiprotein complexes in the inner mitochonrial membrane.

Front 45

In the Islets of Langerhans, what cell types do we have and what hormones do they excrete?

Back 45

Beta - Insulin, Alpha - Glucagon, D - Somatostatin, F or PP - Pancreatic polypeptide

Front 46

What is the structure of insulin?

Back 46

A and B chains joined by disulfide bonds after cleavage of C chain

Front 47

What stimulates insulin secretion?

Back 47

Glucose, amino acids and drugs such as sulphonylureas. In the presence of glucose, glucagon, GI peptides, vasoactive intestinal peptide and acetylcholine also stimulate insulin secretion.

Front 48

What inhibits insulin secretion?

Back 48

Drugs: diazoxide, somatostatin, alpha-adrenergic agents. Maybe fatty acids.

Front 49

What effects do catecholamines (especially epinephrine) have on insulin secretion?

Back 49

Primarily inhibition, with long term stimulation in may stimulate

Front 50

How does metabolism of glucose lead to insulin release in beta cells?

Back 50

Metabolism > depolarization by closing ATP-regulated potassium channels > opening of voltage gated calcium channels > rise in intracellular calcium > exocytosis

Front 51

What does acetylcholine do for insulin release?

Back 51

Stimulates

Front 52

Where does insulin go first?

Back 52

Liver. 50% is extracted in the liver.

Front 53

What does insulin do in order to help make glycogen?

Back 53

It activates glycogen synthase.

Front 54

How does the insulin receptor transduce the signal?

Back 54

Insulin > PI-3 activation > activates PDK > activates PKB > glycogen synthase kinase > glycogen synthase > glycogen

Front 55

Insulin makes more GLUT-4 transporters insert where?

Back 55

muscle and adipose tissue > greater transport of glucose into muscle/adipose tissue

Front 56

Where does glucagon mainly act?

Back 56

liver

Front 57

How is the secretion of glucagon regulated?

Back 57

Inhibited by glucose in alpha cells, free fatty acids, somatostatin. Stimulated by epinephrine. Glucagon secretion can be inappropriately high if insulin is low (Type I DM).

Front 58

How does glucagon act?

Back 58

Interacts with G-protein to increase cAMP

Front 59

What pathways does glucagon promote?

Back 59

glycogenolysis, gluconeogenesis

Front 60

What effect does glucagon have on insulin production?

Back 60

stimulation

Front 61

What effect does somatostatin have in metabolism?

Back 61

It inhibits both insulin and glucagon

Front 62

Epinephrine and norepinephrine have effects that mimic those of what hormone?

Back 62

Glucagon - increase blood glucose

Front 63

What hormones promote lactate production in muscles, due to increased insulin resistance?

Back 63

catecholamines - norepi, epi; cortisol

Front 64

What effect does growth hormone have on insulin sensitivity?

Back 64

Decreases insulin sensitivity

Front 65

What happens in response to carbohydrate feeding?

Back 65

Increased insulin, decreased glucagon, glycogen storage in liver and muscle, decreased fatty acid mobilization from adipose tissue

Front 66

How long does it take for hepatic hepatic glycogen to be depleted?

Back 66

24-28 hrs

Front 67

After 7 days, what is fueling the brain?

Back 67

ketone bodies

Front 68

What situations cause gluconeogenesis to occur?

Back 68

Fasting, vigorous exercise, high protein diet, stress

Front 69

What does the Cori cycle do?

Back 69

Takes blood-borne glucose and makes lactate

Front 70

What are the enzymes of the irreversible rxns of glycolysis?

Back 70

pyruvate kinase, phosphofructokinase, hexokinase

Front 71

What enzymes are used in gluconeogenesis to bypass the irreversible steps of glycolysis?

Back 71

pyruvate carboxylase, phosphoenol pyruvate carboxykinase, fructose 1,6 bisphosphatase and glucose 6 phophatase

Front 72

What enzyme catalyzes the rxn of pyruvate > oxaloacetate?

Back 72

pyruvate carboxylase

Front 73

What enzyme catalyzes the rxn of OAA > PEP?

Back 73

PEP carboxykinase

Front 74

What enzyme catalyzes the rxn of fructose 1,6 bisphosphate to fructose 6 phosphate?

Back 74

Fructose 1,6 bisphosphatase ***RLS***

Front 75

What enzyme catalyzes the rxn on G6P > glucose? Where is it found?

Back 75

glucose 6 phosphphatase; in the membrane of the endoplasmic reticulum in hepatocytes and renal cells

Front 76

What effects does AMP have on fructose 1,6 bisphosphatase and PFK-1?

Back 76

AMP inhibits fructose 1,6 bisphosphatase and activates PFK1

Front 77

What are the 3 steps in glycogen degredation?

Back 77

1. release of glucose 1 phosphate from glycogen (glycogen phosphorylase **key regulatory enzyme**) 2. remodeling of glycogen substrate (debranching enzyme) 3. conversion of glucose 1-phosphate into glucose 6-phosphate

Front 78

In skeletal muscle, what pathway does the G6P enter to serve as a source of energy?

Back 78

glycolysis

Front 79

In liver, what happens to muscle glycogen?

Back 79

It is converted to glucose (glucose 6 phosphotase) to support blood glucose levels

Front 80

Where is glucose 6 phosphatase found?

Back 80

liver

Front 81

What does glycogen sythase do?

Back 81

It catalyzes the transfer of glucose from UDP-glucose to a growing chain.

Front 82

What kind of branches are formed by a branching enzyme?

Back 82

alpha 1,6 linkages

Front 83

Why is branching important?

Back 83

It increases the rate of glycogen synthesis and degredation

Front 84

How is glycogen metabolism regulated?

Back 84

insulin and glucogon

Front 85

How is glycogen synthase allosterically activated?

Back 85

Activated by glucose-6-phosphate

Front 86

What allosterically inhibits glycogen phosphorylase?

Back 86

glucose 6 phosphate

Front 87

How does calcium lay a role in glycogen phosphorylase regulation?

Back 87

Calcium release (active muscle) activates phosphorylase kinase which in turn phosphorylates glycogen phosphorylase making it active

Front 88

What does AMP do to glycogen phosphorylase?

Back 88

It binds to the inactive form and activates it

Front 89

How does the binding of glucagon or epinephrine lead to activation of glycogen phosphorylase?

Back 89

Glucagon/epinephrine activates PKA, which phosphorylates phosphorylase kinase which phosphorylates glycogen phosphorylase

Front 90

What inhibits glucagon?

Back 90

high blood glucose and insulin

Front 91

Glycogen synthase and pyruvate dehydrogenase are activated or inhibited by a high insulin:glucagon ratio?

Back 91

Activated

Front 92

What are the levels of basal glucose production rate for different ages?

Back 92

Neonate - 8-12 mg/kg/min
Infant - 6-8 mg/kg/min
Child - 4-6 mg/kg/min
Adult - 2-4 mg/kg/min

Front 93

How low is too low (hypoglycemia)?

Back 93

Child - 45 mg/dL
Adult - 60 mg/dL

Front 94

What is the treatment for hypoglycemia (child)?

Back 94

2.5mL/kg of D10

Front 95

What are the sites of microvascular disease?

Back 95

kidneys, eyes, nerves

Front 96

What levels define diabetes?

Back 96

Fasting glucose >126, 2hr glucose >200

Front 97

What are some of the symptoms of diabetes?

Back 97

polyuria, polydipsia, blurry vision, weight loss

Front 98

Which has more of a genetic component - type I or type II diabetes?

Back 98

type II

Front 99

What are the "stages" in the development of Type I diabetes?

Back 99

Genetic predisposition, precipitating event, overt immunologic abnormalities, progressive loss of insulin release, overt diabetes, no c peptide

Front 100

What are some of the autoantibodies against insulin/ islet cells?

Back 100

Islet cell autoantibody (ICA), GAD65, IA2, ZnT8

Front 101

What defines an impaired glucose tolerance?

Back 101

Fasting glucose 100-125, OGTT 140-199

Front 102

What percentage of the beta cell mass has to be destroyed for symptoms of diabetes to appear?

Back 102

~90%

Front 103

Microvascular risk is linked to which measure?

Back 103

fasting blood glucose

Front 104

Cardiovascular risk is linked to which measure?

Back 104

OGTT

Front 105

What are the criteria for the diagnosis of DM?

Back 105

Random plasma glucose >200 plus symptoms OR fasting blood glucose >125, OR OGTT >200

Front 106

In what ethnic groups is there a genetic predisposition to DM type II?

Back 106

African-Americans, hispanics, Pima Indians

Front 107

Is there monozygotic twin concordance with DM type II?

Back 107

Yes, 90-100%

Front 108

Which state is more affected in type II DM, the basal state or the first phase of insulin secretion?

Back 108

Acute/first phase - pretty much gone. The basal state and second phase are preserved. Eventually, all insulin secretion is seriously diminished.

Front 109

What are the signs and symptoms of the metabolic syndrome?

Back 109

abdominal obesity, glucose intolerance, hypertension, atherosclerosins, polycystic ovary syndrome, altered carbohydrate metabolism, dyslipidemia, procoagulant state

Front 110

What recombinant human insulins are available and what is their duration of action?

Back 110

(1) Short-acting Regular insulin: (30 min before meals) - Humulin R or Novolin R **can be SubQ or IV; (2) Intermediate Acting: NPH - peaks at 6-7 hours

Front 111

What insulin analogs are available?

Back 111

(1) Rapid acting (food is on the table) - Humalog, Novolog, Glulisine; (2) Long-acting - Glargine (24 hrs), Detemir (17 hours)

Front 112

What is the MOA of sulfonylureas?

Back 112

Close ATP sensitive potassium channels in beta cell membranes; depolarization allows calcium influx which stiumulates insulin secretion

Front 113

What are some sulfonylureas?

Back 113

Glyburide > glipizide > glimpiride (duration of action)

Front 114

What are pros/cons of sulfonylureas?

Back 114

Pros: cheap, can be used early in the course and in combination with other agents; Cons: weight gain, hypoglycemia, lose effectiveness (renal excretion)

Front 115

What is Metformin's MOA?

Back 115

It acts at the liver to help insulin suppress hepatic glucose production

Front 116

What are the pros and cons of Metformin?

Back 116

Pros: effective for insulin resistance, no hypoglycemia, no weight gain, can combo; Cons: GI side effects, risk of lactic acidosis, not good with CHF, renal insufficiency, alcohol, contrast media

Front 117

What is the MOA of the thiazolidinediones?

Back 117

Activation of peroxisome proliferator-activated receptor gamma. Insulin sensitizers, at the level of skeletal muscle and adipose tissue

Front 118

What are some of the thiazolidinediones?

Back 118

pioglizazone (actos) and rosiglitazone which is controversial

Front 119

What are the pros and cons of the thiazolidinediones?

Back 119

Pros: effective for insulin resistance Cons: $$$, edema, CHF, CV events

Front 120

How do the GLP-1 receptor agonists work (Byetta)?

Back 120

It amplifies glucose-stimulated insulin secretion, inhibits glucagon secretion and slows gastric emptying.

Front 121

How does the DPP-4 inhibitor, Sitagliptin, work?

Back 121

It increases the circulating levels of endogenous GLP-1 -> lowers fasting and postprandial glucose

Front 122

How does the amylin analog work?

Back 122

Inhibits gastric emptying, glucagon secretion and reduces short-term food intake.

Front 123

What is our goal for HgA1C in adults?

Back 123

<7%

Front 124

What is the limiting factor in HgA1C goal attainment?

Back 124

episodes of hypoglycemia

Front 125

What is the approximate energy expenditure per kg?

Back 125

25-35 kcal/kg/day

Front 126

What are the percentages of each macronutrient in the average diet?

Back 126

Protein 15%, Fat 35%, Carb 50%

Front 127

How many grams of carbs does the average diet have?

Back 127

262.5 g of carbs

Front 128

What is the energy density of carbohydrates?

Back 128

4kcal/gram

Front 129

What does the glycemic indedx tell you?

Back 129

With 100 grams of given food, what is the area under the blood glucose/time curve

Front 130

What does the epi data say about diets and diabetes?

Back 130

correlation between total carbs, high fructose corn syrup and diabetes

Front 131

What is the relationship between glycemic load, fiber and diabetes?

Back 131

low fiber, high glycemic load -> diabetes

Front 132

What is the long term intervention that best prevents diabetes?

Back 132

increase fiber, low fat, low sat fat, physical activity

Front 133

What are some complications (morbidity) from diabetes?

Back 133

CV disease, retinopathy, neuropathy, amputations

Front 134

A diabetic with a hx of heart attack has approximately what risk of having a MI in 10 years?

Back 134

~50%

Front 135

What is dyslipidemia?

Back 135

Small, dense LDL, decreased HDL, increased triglycerides

Front 136

Why treat cholesterol in diabetes?

Back 136

decrease plaque progression, CV events, mortality (Only done in 25% of patients)

Front 137

What is the BP goal in diabetes?

Back 137

120-130/80 (even lower w/ kidney failure)

Front 138

Patients with diabetes should be taking what for their procoagulant state?

Back 138

aspirin (+ statins, beta blockers, ACE inhibitors)

Front 139

Where do we have aldose reductase and why does it matter?

Back 139

eyes, nerves, kidneys. Glucose > sorbitol, toxicity

Front 140

What is the leading cause of renal failure?

Back 140

diabetes (46% of Type I, 35% of Type II)

Front 141

What is the progression of diabetic nephorpathy?

Back 141

basement membrane thickening, mesanglial expansion, glomerular fibrosis and tubulointerstitial scarring **need to detect microalbuminuria/proteinuria nephropathy in order to intervene - ACE inhibitor**