Biochem Test 4

Front 1

Apo B-100

Back 1

LDL, VLDL, IDL
555,000 Da
VLDL secretion from liver
Ligand for LDL receptor

Front 2

Apo B-48

Back 2

Chylomicrons, Chylomicron remnants
260,000 Da
Chylomicron secretion from intestine

Front 3

Apo C-II

Back 3

VLDL, HDL, Chylomicrons
8,916 Da
Activator of lipoprotein lipase

Front 4

Apo E

Back 4

VLDL, IDL, HDL, Chylomicrons, chylomicron remnants
34,000 Da
Present in excess in B-VLDL patients with type III hyperlipoproteinemia. The sole apoprotein found in HDL of diet induced hypercholesterolemic animals. Ligand for chylomicron remnant receptor in liver and LDL receptor

Front 5

Apo B

Back 5

structural components of lipoproteins

Front 6

Apo C-II

Back 6

Interact w/ cell surface enzymes as cofactors or inhibitors during lipid transport

* activates LPL

Front 7

Apo E or Apo B-100

Back 7

acts as ligands for lipoprotein receptors on the cell surface during lipid transport

Front 8

4 Mechanisms of Hormone Action

Back 8

1. Increase NZ substrate
2. Phosphorylate active site, changing its shape
3. Chance [allosteric affector]
4. Alter protein expression levels

Front 9

Two main Cell Signaling Pathways by Fuel Metabolism Hormones

Back 9

1.) Polypeptide Hormones (Insulin, Glucagon) & Catecholamines (Epi/NE) bind to plasma membrane receptors to initiate action

2. Steroid Hormones (cortisol) pass directly through plasma membrane and exert effects on the cell nucleus

Front 10

3 Basic Types of Signal Transduction Hormones that bind plasma membrane

Back 10

1. Receptor coupling to adenylate cyclase producing cAMP
2. Receptor Kinase activity
3. Receptor coupling to PIP2

Front 11

B-adrenergic receptor for Epi/NE

Back 11

- action through cAMP and PKA
- stim. glycogenesis & gluconeogenesis in mm. & liver
- stim lipolysis in adipose

Front 12

a-adrenergic receptor

Back 12

- action through phospholipase C
- use IP3 & DAG 2nd messengers
- stim. vascular & sm contraction

Front 13

Methylxanthines & Caffeine

Back 13

- inhibit cyclic nucleotide phosphodiesterase which recycles cAMP
- Prolongue the effects of Glucagon

Front 14

2 problems with presented in TG digestion

Back 14

1. Lipids are poorly soluble
2. Hydrolysis of lipids releases products that tend to aggregate, blocking uptake by intestinal cells

* Bile salts fix this problem, stimulated by CCK in duodenum

Front 15

2 molecules that conjugate Bile salts

Back 15

- Taurine
- Glycine

* lowers pKA, so they aren't charged at physiological pH
* Makes bile more soluble

Front 16

Critical Bile Salt level

Back 16

- concentration of bile salts at which micelles will form

Front 17

Dehydroxylation of Bile salts

Back 17

- at pos. 7
- makes bile salt less soluble and therefore more likely to be excreted in the feces
- Called secondary bile salts when dehydroxylated

Front 18

Secretin

Back 18

- Stim. release of bicarb to neutralize acidic stomach chyme in response to increased acidity in the SI

Front 19

Colipase

Back 19

- Acts in concert w/ pancreatic lipase
- anchors pancreatic lipase to lipid micelle
- activates pancreatic lipase

Front 20

Pancreatic Lipase

Back 20

- Breaks TG into --> 2FA & a monoacylglycerol
* the FA are cleaved from positions 1 & 3 on TAG

- monacylglycerol and FA can be absorbed by intestinal epithelial cells

Front 21

Olestra

Back 21

- Fat substitute
- Sucrose backbone
- hard to digest by pancreatic lipase, therefore most passes into feces

* Creates a problem b/c you don not absorb Vit ADEK which are fat soluble vitamins that are coabsorbed with dietary lipids

Front 22

Orlistat (xenical or Alli)

Back 22

- Pancreatic Lipase Inhibitor used for weight loss
- forms a covalent ester bond with the active site of Serine 152 of human pancreatic lipase

Front 23

Short & Medium Chain FA intestinal absorption

Back 23

- don't have to be in micelles, pass freely across the plasma membrane into intestinal epithelial cells
- Bind to serum albumin and transported across epithelial cells

Front 24

Acyl CoA Synthetase

Back 24

- Converts FA to Fatty Acyl CoA
2 Places
1.) TG resynthesis in intestinal epithelial cells
2.) Activate FA for B-Oxidation

*FACoA is a CoA thioester
* 2 ATP equivalents are consumed in convervting FA-->FACoA

Front 25

Differences in TG resynthesis in Liver/adipose and in Intestinal epithelial cells

Back 25

Intestinal Epithelial Cells
- 2MG reacts w/ individual FACoA first making diacylglycerol then finally TAG

Liver/Adipose
- Phosphatidic acid is the intermediate utilized for TG formations (2-MG takes it's place in intestinal cells)

Front 26

Chylomicrons

Back 26

- Ball of TG, Phospholipids, Cholesterol, Cholesterol esters, fat-soluble vitamins, & Apo-Proteins

- Formed in intestinal cells after initial lipid digestion by and TG resynthesis in intestinal epithelial cells

* if TG were no packaged into chylomicrons they would block blood flow

Front 27

Four lipid classes in lipoproteins

Back 27

H-Philic/Polar --> exterior
- Phospholipids
- Cholesterol

H-Phobic/nonpolar --> Interior
- TAG
- Cholesterol Esters

Front 28

TAG Transport

Back 28

Chylomicron & VLDL

Front 29

Cholesterol Transport

Back 29

LDL

Front 30

Cholesterol Reverse Transport

Back 30

HDL

Front 31

MTP (Microsomal Triglyceride Transfer Protein)

Back 31

- accelerates the transport of lipids across the ER membrane into the ER lumen during chylomicron synthesis.

- Also helps add Apo-B 48 during chylomicron assembly

Front 32

Abetalipoproteinemia (Bassen-Kornzweig Syndrome)

Back 32

- Lack of MTP activity
- reduces formation of both chylomicrons & VLDL
- leads to lipid malabsorption
- Fat-Soluble Vitamin deficiency
- Ataxia & nerve issues b/c reduced myelination

Front 33

2 Proteins required for Nascent Chylomicron maturation

Back 33

- Apo CII
- ApoE
* both come from interactions with HDL in blood
- now considered mature chylomicrons

Front 34

Lipoprotein Lipase (LPL) & what activates it?

Back 34

- In Blood
- Breaks down Chylomicrons into FA & Glycerol allowing absorption into Liver, muscle, & adipose
- activated by Apo CII on mature chylomicrons

Front 35

What Apo protein is recognized on chylomicron remnants by liver?

Back 35

Apo E

Front 36

2 reasons why TAGs are very efficient at storing fuel

Back 36

1.) stored in anhydrous form
2.) more chemically reduced than AA or monosaccharides

Front 37

Metabolic Fates of FACoA

Back 37

1.) B-Ox (Energy)
2.) Plasma membrane (Cell Structure)
3.) TAGS (Storage)

Front 38

CPT II Deficiency

Back 38

- Pt.s cannot process LCFA for energy
- symptoms: myoglobinuria, weakness, hypoglycemia
- FA build up in blood & muscle causing damage

Front 39

One Round of B-Ox

Back 39

1 NADH
1 FADH
1 Acetyl CoA
2C shorter Fatty Acyl CoA

Steps:
-Oxidation
-Hydration
-Oxidation
-Thiolysis

Front 40

Most Common FA B-Ox. Defect

Back 40

Medium Chain Acyl-CoA Dehydrogenase (MCAD)

- Acylcarnitines rise in blood & urine
- Sleepiness, vomiting, hypoglycemic, hypoketotic, fatty liver, elevated blood levels of MCFA
- treatment is to eat a low fat, high carb diet, and avoid long times between eating to avoid FA ox for E

Front 41

Jamaican Vomiting Disease

Back 41

- Unripe fruit contains Hypoglycin, a toxin that inactivates short & medium chain acyl-coa dehydrogenases
- Severe hypoglycemia which may be fatal

Front 42

Additional enzymes require for unsaturated FA Oxidation

Back 42

1.) Enoyl-CoA isomerase (used twice in Polyunsat.)
2.) 2,4 Dienoyl-CoA-Reductase (uses NADPH)

* Monounsaturated only require enoyl-CoA isomerase, and only use it once

Front 43

3 important control points of B-Ox.

Back 43

1.) Reg. of CPT-I in liver
2.) Release of FA from adipocytes
3.) Levels of ATP & NADH

Fed state - Storage/FA synth
Fasting state - FA ox. for E

Front 44

Malonyl-CoA

Back 44

- Inhibit CPT-I in fed state
- A precursor for FA synth made from acetyl CoA by acetyl CoA carboxylase

Front 45

Hormone Sensitive Lipase

Back 45

- releases FFA into blood during fasting state as a response to glucagon increase & insulin decrease

Front 46

alpha-oxidation

Back 46

- used for branched chain FA
- occurs in peroxisome
- first cleaves at alpha carbon releasing a 1C unit
- now beta oxidation proceeds alternating release of Acetyl-CoA(2C) & Propionyl CoA(3C)

Front 47

omega-oxidation

Back 47

- FA oxidized at omega end (opp. end normally used in B-ox)
- FA are converted to dicarboxylic acids that can be released into urine (b/c they are now more soluble, neg. charge on each end) or beta-oxidized
- normally a minor pathway, but more important when B-ox is defective.

Front 48

Zellwegger's Syndrome

Back 48

- Defective Peroxisomal biogenesis
- can't process VLCFA & branched chain FA
- fatal after 6 months of age
- negatively affects liver & brain development
- no treatment

Front 49

Refsum's Disease

Back 49

- Deficiency in phytanoyl CoA Hydroxylase (a-oxidation)
- elevated phytanic acid in blood and tissues
- neurological damage (blind & deaf)
- treat w/ low phytanic acid diet ( no green vegetables)

Front 50

Liver lacks this enzyme and therefore can't use KB for E

Back 50

- Succinyl-CoA transferase
- requires succinate

Front 51

Galactose 1-P accumulation inhibits....?

Back 51

-Phosphoglucomutase
-preventing formation of UDP-Glucose, the precursor for UDP-Glucutonate, glycogen, glycoproteins, ect

Front 52

a-lactalbumin

Back 52

- 1 of 2 subunits in lactase synthase (the other is galactosyltransferase)
- Synthesized after childbirth in response to prolactin
- Lowers Km of galactosyltransferase for glucose to increase the rate of lactose synthesis
- acts as a specifier protein by altering substrate specificity

Front 53

2 subunits of Lactase Synthase

Back 53

- Galactosyltransferase
- a-lactalbumin

Front 54

O-linked Glycoproteins are attached to .....(fxnal group) of ..... (AA)

Back 54

- OH
- Ser/Thr

Front 55

N-linked Glycoproteins are attached to .... (fxnal group of .... (AA)

Back 55

- N
- Asn

Front 56

2 Classes of N-linked Oligosaccharides

Back 56

1.) high Mannose
- only 2 GlcNAc & up to 9 Mannose
- Complex

Front 57

I-Cell Disease

Back 57

-Deficient Phosphoatransferase, which is required for tagging the terminal mannose w/ p-group
- therefore NZ secreted to EC space instead of lysosome
- lysosomes become engorged and form inclusion bodies

Front 58

Tay-Sachs

Back 58

-Lysosomal Storage Disease
-NZ Def: Hexosaminidase A
- Mental Retardation, blindness, Cherry Red spot on macula, death between 3 &4

Front 59

UDP-Glucuronate is a precursor of...

Back 59

- Glucuronides
- Bilirubin Diglucuronide (conjugated)
- Proteoglycans & glycoproteins

Front 60

Reasons for increased bilirubin

Back 60

- Hemolysis (G6PD deficiency)
- Liver Disease
- Premature Infants (low levels of conjugating enzyme)

Front 61

Amino sugars used in the synthesis of GAGs are all derived from...?

Back 61

Glucosamine-6-Phosphate