Block 3 Week 3

Front 1

what are risk factors for DMT2

Back 1

obesity, some ethnicities

Front 2

how does insulin act on cells

Back 2

stimulates insertion of GLUT4 (also exercise will do this)

Front 3

what is a diagnostic tool for average blood glucose

Back 3

glycosylated Hb (HbA1c)

Front 4

most common source of death from diabetes

Back 4

micro/macro-vascular problems, leading to CV disease

Front 5

what is primary storage/synthesis site of glycogen

Back 5

liver, muscle

Front 6

what is the unique property of neurons regarding GLUT3 transporters

Back 6

GLUT3 glucose transport does not depend on insulin; Km is low, meaning that GLUT3 has high affinity for glucose and can maintain transport even at low glucose levels

Front 7

what happens to neuron GLUT3 transporter under high glucose levels

Back 7

receptors are reuptake into the cell

Front 8

what is unique about glucokinase

Back 8

higher Vmax, not inhibited by G6P

Front 9

describe glycolysis pathway, the four primary products

Back 9

glucose > G6P > F6P > F1,6P

Front 10

how is glucokinase regulated

Back 10

F6P inhibits glycolysis > glucokinase to translocate into nucleus; glucose stimulates release of glucokinase from the inhibitory factor in nucleus

Front 11

describe glucokinase effects in beta cells

Back 11

stimulates insulin secretion by increasing levels of ATP through glycolysis

Front 12

what organs participate in gluconeogenesis

Back 12

liver, kidney

Front 13

what enzyme allows glucose to be released

Back 13

G6phosphatase

Front 14

what is glycogen synthetase

Back 14

elongates glycogen chains

Front 15

can muscle release glucose

Back 15

no, does not have G6phosphatase, but can convert to lactate so liver can make glucose via gluconeogenesis

Front 16

can adipose tissue release glucose

Back 16

no, can release glycerol or fatty acids to be synthesized into glucose by liver (fatty acid will generate energy via nother pathway)

Front 17

what are precursors for gluconeogenesis

Back 17

lactate, amino acids, or glycerol (three-carbon skeletons)

Front 18

describe glucose sensor in pancreatic beta cells

Back 18

glucose initiates glycolysis > increase ATP > depolarizes cell > release insulin-filled granules in quanta-released manner

Front 19

function of lipase

Back 19

convert triglyceride to fatty acid and glycerol

Front 20

cholesterol is precusor for what three general classes of molecules

Back 20

1. cholesterol esters, 2. bile salts, 3. steroid hormones

Front 21

consequences of bile duct obstruction

Back 21

1. pancreatitis, 2. gallstones, 3. loss of fat-soluble vitamins

Front 22

describe absorption of fatty acids (short vs long)

Back 22

short absorbed directly into bloodstream; long-chain repackaged into TAG and packaged into chylomicrons, enter the lymph

Front 23

what is the primary method of excreting excess cholesterol

Back 23

5% of bile secretion is lost, this is primary method

Front 24

what is purpose of ezetimibe

Back 24

lower cholesterol

Front 25

pathogenesis of abetalipoproteinemia

Back 25

inability to secrete chylomicrons > cannot absorb fats/vitamins

Front 26

describe GLUT4 transporter

Back 26

located on muscle/adipose cells; insulin recruits vesicles containing GLUT4 transporters

Front 27

where is glucokinase found, and its function

Back 27

liver (synthesize glycogen), pancreas (glucose sensor)

Front 28

what is the primary regulatory mechanisms in glycolysis

Back 28

energy levels (ATP, ADP, citrate from TCA cycle)

Front 29

what is PFK1 enzyme

Back 29

converts F6P to F1,6P

Front 30

how is PFK1 regulated

Back 30

energy-related metabolites (ATP/AMP/citrate)

Front 31

what is the bifunctional enzyme and its regulation

Back 31

insulin (uptake energy) will dephosphorylate PFK2 and increase glycolysis; glucagon (release energy) will phosphorylate PFK2 and inhibit glycolysis, will also increase gluconeogenesis

Front 32

where is bifunctional enzyme located

Back 32

only in liver; heart has different variant with opposite effect (phosphorylation increases glycolysis)

Front 33

what is pyruvate kinase, and its regulation

Back 33

catalyzes last step to form pyruvate; inhibited by glucagon, so will inhibit glycolysis

Front 34

what is pyruvate dehydrogenase, and its regulation

Back 34

catalyzes formation of acetyl CoA; regulated by Ca2+ from muscle contraction and energy metabolites (lots of energy available, no need to do anything)

Front 35

where does G6phosphatase activity take place

Back 35

in ER lumen

Front 36

describe last step of releasing glucose

Back 36

1. G6P transported into ER, 2. converion to glucose, 3. individual transports remove each component from ER lumen

Front 37

describe pathogenesis of van gierke disease

Back 37

defective G6P transporter or G6phosphatase, cannot increase blood glucose

Front 38

what is treatment for van gierke disease

Back 38

glucose infusion or starch

Front 39

what are the two important enzymes make/break glycogen

Back 39

synthase and phosphorylase

Front 40

describe regulation of synthase and phosphorylase

Back 40

phosphorylation will activate phosphorylase and increase glycogen breakdown, dephosphorylation will activate synthase and increase glycogen synthesis; regulated by energy metabolites, glucagon, and insulin

Front 41

what is the rate-limiting step in lipogenesis

Back 41

conversion of acetyl CoA > malonyl CoA by carboxylase

Front 42

how is lipogenesis regulated

Back 42

excess carbohydrates result in high level of glycolysis, and high levels of acetyl CoA and citrate (intermediate metabolites) will result in increased levels of fatty acid synthesis

Front 43

describe insulin/glucagon regulation of lipogenesis

Back 43

insulin signals high energy, will increase fatty acid synthesis; glucagon/epi signals low energy, will inhibit lipogenesis

Front 44

describe regulation of lipolysis

Back 44

enzyme hormone-sensitive lipase (HSL) accelerates breakdown of TAG and mobilization of fatty acids; insulin will inhibit lipolysis; stress/epinephrine/glucagon will activate HSL and increase fatty acid

Front 45

where is lipoprotein lipase expressed

Back 45

ECs, adipose tissue, muscle tissue

Front 46

what is function of LPL

Back 46

converts TAG > fatty acid

Front 47

what is the effect of insulin on LPL

Back 47

increases expression, so fatty acid can enter adipose tissue for storage

Front 48

pathogenesis of hyperchylomicronemia

Back 48

defective LPL causes accumulation of chylomicrons

Front 49

consequences of hyperchylomicronemia

Back 49

pancreatitis, skin eruptions

Front 50

what is function of ABCA1 transporter

Back 50

transports cholesterol/lipids for HDL synthesis

Front 51

where does HDL synthesis take place

Back 51

liver, intestine

Front 52

pathogenesis of tangier disease

Back 52

defective ABCA1 transporter > very low HDL levels

Front 53

what two things can increase HDL

Back 53

niacin, exercise

Front 54

low HDL is at risk for what

Back 54

cardiovascular disease, atherosclerosis

Front 55

pathogenesis of familial hypercholesterolemia

Back 55

defective LDL receptor causes eleveated levels of cholesterol

Front 56

what are consequences of hypercholesteriolemia

Back 56

skin boils, risk of MI, heart attack

Front 57

describe regulation of LDL receptor

Back 57

binding internalizes receptor and LDL separates > LDL is degraded to release cholesterol in lysosomes > cholesterol inhibits synthesis of LDLR and cholesterol synthesis (HMG-CoA reductase) > less cholesterol absorption and less cholesterol synthesis

Front 58

what is the role of HMG-CoA reductase

Back 58

cholesterol synthesis

Front 59

what are early predictors of DMT1

Back 59

autoimmune antibodies against pancreatic cells, decreased protein C

Front 60

what is protein C

Back 60

cleaved portion of proinsulin; used to measure insulin level

Front 61

describe secretion of insulin

Back 61

proinsulin from pancreas is cleaved to make 1. insulin, 2. protein C

Front 62

describe how hyperglycemia develops in diabetes

Back 62

no insulin at the liver causes 1. gluconeogenesis, 2. glycogenolysis, 3. TAG breakdown to supply precursors

Front 63

describe effects of no insulin on muscle

Back 63

no insulin prevents expression of GLUT4 > muscle cannot make ATP > K+ depletion

Front 64

describe effects of hyperglycemia on brain

Back 64

elevated glucose causes downregulation of GLUT1

Front 65

describe effects of hyperglycemia on renal system

Back 65

osmotic diuresis > dehydration, volume depletion

Front 66

describe pathogenesis of ketoacidosis in diabetics

Back 66

no insulin > HSL becomes activated > high TAG breakdown, high fatty acid > 1. increase cholesterol/lipid synthesis (atherosclerosis), 2. fatty acid oxidized for energy > produces ketone bodies > acidosis

Front 67

what are consequences of hyperlipidemia

Back 67

1. atherosclerosis, 2. MI/heart attack risk, 3. diabetes

Front 68

describe how plaque forms in hyperlipidemia

Back 68

LDL oxidized and engulfed by macrophage > engorgement leads to fatty streak > plaque

Front 69

describe function of HDL in regard to fatty streaks and macrophages

Back 69

HDL suppresses LDL oxidation and removes cholesterol from macrophages > brings to the liver

Front 70

describe mechanism of action of statins

Back 70

competitive inhibition of HMG-CoA reductase > reduced cholesterol synthesis

Front 71

what are the changes that occur with statin treatment

Back 71

1. reduced cholesterol synthesis, 2. increase LDLR synthesis (due to less negative feedback from lower cholesterol), 3. increased HMG-CoA reductase synthesis, 4. increase secretion of cholesterol into bile

Front 72

how is blood LDL controlled, where

Back 72

cholesterol-level-dependent protein activates transcription of LDLR (in the liver)

Front 73

what is the treatment for familial hypercholesterolemia

Back 73

statins if heterozygous; liver transplant if homozygous mutation

Front 74

name three methods to treat high cholesterol

Back 74

1. statins, 2. niacin, 3. bile acid sequestrant

Front 75

what two effects does niacin have

Back 75

1. increase HDL, 2. decrease LDL by blocking fat breakdown

Front 76

how does bild acid sequestrant work

Back 76

binds to bile acid to prevent reabsorption > increase in bile acid production results in more cholesterol secretion > lower cholesterol increases LDLR synthesis (feedback) > lower cholesterol