Exam 2 Flashcards

Question

FA Phase 1 - Citrate Shuttle

Answer 1

* High [ATP] and [NADH] inhibit isocitrate dehydrogenase * Citrate accumulates, goes to cytosol * Glucose, insulin stimulate ATP:Citrate lyase * Polyunsaturated fatty acids (PUFA), leptin inhibit ATP:Citrate lyase

Answer 2

brain or in cells that lack mitochondria

Answer 3

acetyl-CoA + OAA --(citrate synthase)--\> citrate can be shuttle out of mito and release reactants into cytosol acetyl-COA = precursor to make fat in cytosol citrate = allosteric activactor of 1st rxn in FA synth

Answer 4

•serum albumin to liver and muscle

Answer 5

Derivatives of ceramide an ester between a fatty acid and sphingosine, an amino alcohol The backbone of = NOT glycerol * long-chain amino alcohol sphingosine A fatty acid is joined to sphingosine via an amide linkage A polar head group is connected to sphingosine by a glycosidic or phosphodiester linkage

Answer 6

Glucose 6-Phosphatase (G 6-Ptase) ## Footnote Releases free glucose --\> blood Not in Muscle Muscle does not maintain blood glucose homeostasis Transmembrane Endoplasmic Reticulum protein

Answer 7

toxic to optic N and can produce blindness high doses = fatal

Answer 8

•congenital generalized lipodystrophy (absence of adipose tissue and fatty liver)

Answer 9

spiked drink - common in antifreeze ---\>formaldehyde toxic to optic nerve and can produce blindness. In high doses, formaldehyde may be fatal

Answer 10

signal through multiple second messengers and their effects are determined by specific receptor subtypes in target tissues ## Footnote Prostanoids Signal Via GPCR

Answer 11

* non-selective, reversible COX inhibitors (e.g., ibuprofen) * Analgesic, anti-inflammatory and antipyretic * Inhibit the production of both PG and TX

Answer 12

* SGLT-1 and SGLT-2 for glucose absorption from intestines and kidney * Use of SGLT-2 inhibitors to prevent renal reabsorptionà lower blood glucose

Answer 13

F1P -\> g3p -\> -\> pyr-\> acetyl-coa-\> citrate-\>--\>--\> fats-\> VLDL fats + increase [VLDL] -\> obesity, dyslipidemia

Answer 14

•main nutrient for brain, RBC and tissues with low mitochondria

Answer 15

liver * rapid degrad for blood gluc homeo M * rapid response to M E for contraction * after heavy exercise, glycogen usually lasts ~4 hrs * •Usually ~20 mile mark:”hitting the wall” * FA becomes source of EL 130 ATP @ C16 quick response to glucagon/epi

Answer 16

−Allows individuals to produce endogenous enzyme −Recommended for MPS I (H, H/S)

Answer 17

Because pyruvate does not proceed to Acetyl-CoA, it is shunted to other pathways that produce lactic acid and alanine

Answer 18

•in the matrix of mitochondria

Answer 19

1.Lactate --\> exported * •pH_i alkaline * •pH_e acidic 2. Increase in HIF-1a = increase in angiogenesis for tumor 3. Lactate has immunosuppresive role * T-cell proliferation * cytokine production * cytotoxic activity of CD8+ cells (tumor infiltrating lymphocytes)

Answer 20

sweeter: •173 vs 100 Sweetness value

Answer 21

* beet or cane, high fructose corn syrup, fruits, and honey. * 10% of Western diets

Answer 22

* Removing ROS from cells (especially Red Blood Cells) * Maintains reduced state of –SH groups in proteins * preventing their oxidation to S-S --\> Denaturation --\> Heinz bodies that attach to RBC membranes •Prevents oxidation of membrane proteins in RBC and prevents deformability * leads to enlarged spleen

Answer 23

derivatives of cholesterol - made in liver * Conjugated to glycine or taurine (a sulfated, nonproteinogenic amino acid) * Needed for absorption and transport of fat-soluble vitamins * Only significant way to remove cholesterol from body is via bile salts bile salts = deprotonated bile acids (pka 2-4)

Answer 24

* Defects in α-galactosidase A * Pain in hands and feet * Inability to sweat * clusters of small, dark red spots on the skin (angiokeratomas) * Corneal opacity, hearing loss * Progressive heart and kidney damage * Enzyme replacement therapy available

Answer 25

ØCYP is a “superfamily” of related Heme containing enzymes ØIncorporate 1 atom of O into a substrateà OH 1 atom of O into H2O R-H +O2+NADPH + H+à R-OH + H2O + NADP+ (R= Xenobiotic (toxins),Steroid, Bile Acid, Vit D) ØProduct is more polar and more soluble: can be excreted(especially drugs and toxins) ØNADPH is needed as reducing equivalent

Answer 26

•located in the ER

Answer 27

* Relatively insoluble in water * Soluble in non-polar solvents (e.g., chloroform, ether)

Answer 28

watery mix of organic and inorganic cmpds organic cmpds: lecithin, cholesterol, bile salts bilirubin: catabolite of Hb •Released from gallbladder in response to cholecystokinin (produced from lower duodenum and jejunum) and aids in emulsification, digestion and absorption of lipids

Answer 29

hyperglycemia = increase [sorbitol] due to high [gluc] = increase osmosis = swell retina, lens, N ## Footnote peripheral N-pathy diabetic retinopathy macular edema --\> poor vision

Answer 30

* Made only in hepatic mitochondria * Liver lacks thiophorase and so, cannot catabolize ketone bodies

Answer 31

\*The 2-series, derived from arachidonate, are the most abundant eicosanoids

Answer 32

* Used to make Heme (Hb, Cytochromes) * High energy-thioester --\> hydrolyze --\> GTP

Answer 33

Allosteric ## Footnote * ACC is inactive as a dimer and active as a polymer * Citrate promotes polymerization of ACC * LCFA-CoA inhibit the active polymer formation

Answer 34

1. Makes Acetyl-CoA via PDHC 2. Makes Alanine via ALT 3. Makes Lactate via LDH 4. Makes Oxaloacetate via Pyruvate Carboxylase

Answer 35

normal 5mM [Glucose] * hexokinase (Km=0.1mM) phosphorylates glucose for metabolism. blood glucose levels rise * hexokinase is saturated * glucokinase (Km=10mM) will become active to help prevent hyperglycemia.

Answer 36

•When the FA chain length on ACP-SH reaches 16 carbons, intrinsic Thioesterase I activity of FAS releases the palmitate • * In lactating mammary epithelial cells, Thioesterase II – a discrete cytosolic protein – hydrolyzes shorter chain length FA (8-12C) from FAS complex * For infants, shorter chain FA in mother’s milk are easier to digest

Answer 37

NO is important vasodilator of smooth muscle NO --\> (+) GUANYLATE CYCLASE -\> INCREASE Cgmp --\> ACTIV Protein kinase G --\> P Ca2+ chann --\> decrease in Ca2+ txp --\> decrease in Ca2+ dependent MLCK --\> inactiv smooth M contraction = dilation

Answer 38

lipids have little solubility of H20 (minimal polarity) increase [monomeric lipids] avail for absorption via micelles/vesicles Unstirred water layer

Answer 39

“fruity”

Answer 40

1. Hexokinase 2. PFK-1\* (Phosphofructokinase-1) -- rate-lim step 3. Pyruvate Kinase

Answer 41

* oxidation of a.a. side chains * protein cross-linking * protein fragmentation

Answer 42

iduronate sulfatase deficiency x-linked coarse features, hepatosplenomegaly no corneal clouding! (how to diff from MPS-I)

Answer 43

* Malate-Aspartate Shuttle feeds NADH into Complex 1 of ETCà 3ATP/NADH * Glycerol 3-P Shuttle converts the NADH into FADH2 which feeds into Complex II of the ETCà 2ATP

Answer 44

A.Glycerol kinase

Answer 45

danger of H2O2= ready conversion to the reactive hydroxyl radical (OH-) * attacks memb = deform cytoskel = lysis = lemolytic anemia * either by exposure to UV * by interaction with transition metal ions e.g. Fe, Hb Fe+2---\>Fe+3 +e-, H2O2 + e- ---\> OH.

Answer 46

X-linked E1 alpha gene

Answer 47

In liver: (Main fructose metabolizing organ) * **Not in skeletal muscle, adipose, RBC** Bypasses PFK-1 Fructokinase (low Km for fructose) --\> F1P Aldolase B --\> Glyceraldehyde and DAHP = less ATP made using this pathway * only DHAP can continue as G3p * Glyceraldehyde needs to be converted using Triose kinase --\> G3P

Answer 48

LT receptor antagonists are the most specific of the group and are expected to have the fewest side effects. Steroids block the formation of all eicosanoids and lipoxygenase inhibitors block the production of all LT as well as HETE.

Answer 49

* The committed and rate-limiting step of FA synthesis * Activated by citrate, insulin * Inactivated by LCFA, PUFA, glucagon, epinephrine, AMP

Answer 50

•promotes platelet aggregation and vasoconstriction in arterioles produced by platelets

Answer 51

in mitochondria Formation of OAA from Pyruvate ## Footnote anapleurotic reaction: replenishes OAA Acetyl-CoA: an allosteric activator Energy required: ATP Biotin deficiency(rare) could affect gluconeogenesis

Answer 52

* NADH, CO2 * High energy succinyl-CoA: importance = * Used to make Heme (Hb, Cytochromes) * can hydrolyzed --\> GTP •aKGDH (parallel to PDH complex) * Complex:3 Enzymes and 5 cofactors * Also inhibited by Arsenic: lipoic acid

Answer 53

GNG b/c.... large [NADH] * LDH: Pyruvate +NADH --\> Lactate +NAD+ * Malate DH: OAA +NADH --\> Malate +NAD+ * **Decrease in Precursors for Gluconeogenesis** Low blood glucose--\>rapid heart beat Increase in Lactate (metabolic acidosis) --\>hyperventilation (respiratory compensation)

Answer 54

* 3 Enzymes: E1,E2,E3 * 5 Cofactors needed from vitamins: –TPP (Thiamine pyrophosphate): Thiamine (Vit B1) –FAD+: Riboflavin (Vit B2) –NAD+: Niacin (Vit B3) –Coenzyme A : Pantothenic Acid (Vit B5) –Lipoic Acid

Answer 55

A combination of a COX2 selective drug and low dose aspirin (or picotamide) to treat pain and keep the balance between prostacyclin and TXA2 levels.

Answer 56

atp * With an adequate supply of oxygen, the cells use ADP, Pi, and H+ in the mitochondria to reconstitute ATP. accumulation of **H+** and Pi in the cytosol * ATP --\> ADP + Pi + H+ lactate accumulation due to inab pyr to continue metab in mito

Answer 57

•Pancreatic insufficiency * −CF * −Panc ca •cholestasis * Decreased bile flow usu due to Gall stones •Inflammatory bowel diseases * −Celiac sprue (gluten sensitivity) * −Crohn disease (autoimmune) * −Bowel resection

Answer 58

Acetyl CoA * Palmitic acid (16:0) is first made * All other FA made from palmitoyl CoA −By elongation −By desaturation

Answer 59

* irreversibly blocks COX 1 and 2 * Analgesic, anti-inflammatory and antipyretic * Inhibits the production of both PG and TX

Answer 60

* Zileuton(Zyflo®), a 5-lipoxygenase inhibitor (will inhibit production of LT as well as 5-HETE) * Pranlukast (Ultair®), Zafirlukast (Accolate®), Montelukast (Singulair®) are CysLT receptor antagonists * Steroidal anti-inflammatory drugs like hydrocortisone, prednisone, and betamethasone, appear to act by blocking LT and HETE production by suppressing phospholipase A2 activity and interfering with the mobilization of arachidonic acid, the substrate for lipoxygenases

Answer 61

•Catalyzed by distinct glycosyltransferases specific for each sugar NDP-Sugar + Protein → Protein-Sugar + NDP

Answer 62

* Hexose monophosphate shunt (PPP) * Malic enzyme

Answer 63

: Low energy * AMP activates glycogen phosphorylase b WITHOUT phosphorylation by PKA * Low O2/energy ,muscle can still undergo glycogenolysis àATP

Answer 64

ØMitochondrial hydroxylation reactions of substrates * Hydroxylation of steroids * Mitochondrial Cyto P450 * Steroid producing organs, placenta, ovaries, testis, adrenal cortex * Bile acid synthesis: liver * Hydroxylation in Vit D synthesis: kidney ØMicrosomal hydroxylation reactions: detoxification of toxins, drugs Ø

Answer 65

via pancreatic cholesterol esterase into cholesterol + FA free colesterol absorbed in duodenum and jejunum with NPC1-L1 txpor protein

Answer 66

* promote inflammatory responses * Individual PGs may promote (e.g., PGE2) or inhibit (e.g., PGI2) contraction of certain smooth muscles by interacting with different receptors

Answer 67

ØPresent in peroxisomes in almost all cells ØRemoves H2O2 without producing free radicals

Answer 68

Short chain FA (SCFA) \< 6 carbons Medium chain FA (MCFA) 6-12 carbons * lactating mamm glands = easy to digest for infant Long chain FA (LCFA) 14-22 carbons Very long chain FA (VLCFA) \> 22 carbons * 34 in CNS, partic in myelin

Answer 69

•synthesize glucose so as to maintain blood glucose levels within fasting range of 70-110mg/dl (~5mM)

Answer 70

rate pyr form \> rate of use by mito * due to rapid inc in metab rate * o2 delivery to mito declines = hypoxia rate gluc metab \> ox capacity of mito * admit of catecholamines (epi) * errors in metab

Answer 71

* Carrier rate is 1 in 30 among Ashkenazi Jewish population * Defect in Hexosaminidase A * Buildup of ganglioside GM2 in nerve cells * Profound mental and physical retardation * Cherry red spot on macula

Answer 72

* Produced from chlorophyll and a component of dairy products and some fish * Oxidation of α-carbon produces pristanic acid * •2,6,10,14-Tetramethylpentadecanoic acid * •Can be metabolized by β-oxidation

Answer 73

• Divided into 2 parts: –Part 1: Oxidative reactions: Irreversible –Part 2: Nonoxidative: Reversible * No ATP used or made * Present in all cells * Cytoplasmic

Answer 74

Conversion of Pyruvate to Lactate under Anaerobic Conditions

Answer 75

live lysosomes, alpha-toxin of clostridia and other bacilli PIP2 system = producing second messengers

Answer 76

* Short term regulation * Allosteric regulation (citrate, LCFA) * Covalent modification (glucag, ins) * Long term regulation * Gene expression * High carb/low fat diet (↑) * Fasting or High fat diet (↓)

Answer 77

ØLactase deficiency: Primary * Presents with diarrhea, bloating, cramps * Can increase with age * More than three quarters of the world's adults are lactose intolerant * Can vary within different ethnic populations * 90% of adults of Asian or African descent * 25% of Northern European descent (e.g. Dutch, Scandinavian) * Up to 75% of the world population has some lactose intolerance ØLactase deficiency: Secondary * Due to intestinal injury * First activity lost and last to recover

Answer 78

* Andersen:Type IV: loss of branching * Cori:Type III: loss of debranching

Answer 79

•coarse facial features, skeletal abnormalities, mental retardation and heart valve and respiratory problems

Answer 80

ØAllosteric : + Glucose 6-P ØCovalent: - dephos/+phosph via hormonal regulation by glucagon/insulin

Answer 81

pyr -(pyr carboxylase)- oaa_m -(malate DH)- malate_m - malate_i -(malate DH)- oaa_c-(PEP carboxykinase) - pep

Answer 82

* NO + ROS --\> OH· * iNOS is induced by bacterial lipopolysaccharides and gamma-interferon released during infections

Answer 83

cell surfaces, basement membranes

Answer 84

Type VI ## Footnote •Liver phosphorylase deficiency ØUsually only partial: complete would be fatal ØExtreme hepatomegaly ØHypoglycemia milder than in Type Ia

Answer 85

* Essential components of all membranes * Located on the outer leaflet of the plasma membrane * Found in greatest amounts in nerve cells * Are antigenic: the carbohydrate portion being the antigenic determinant (e.g., blood group antigens) * Can serve as cell surface receptors

Answer 86

* G6PDH is an enzyme in HMPS that produces NADPH * A deficiency in NADPH, especially in the RBC, prevents the reduction of glutathione to GSH which then prevents the removal of H2O2 by Glutathione Peroxidase (which requires GSH) * H2O2 can attack RBC=lysis=hemolytic anemia

Answer 87

ØPhosphorylation effectively traps glucose in cell ØReaction is irreversible

Answer 88

•Primary carnitine deficiency * •Nutritional (e.g., Vegans) * •Carnitine transporter defects * •Hepatic synthesis defects * •Renal reabsorption defects * •Mild to severe muscle cramps and weakness

Answer 89

tumor cells use glycolysis to make lactate as its main metabolic pathway even in the presence of oxygen •Up to 90% of glucose --\> lactate (up to 40X more than normal) LACTIC ACIDOSIS via LDH

Answer 90

cartilage, tendon, bones

Answer 91

mitochondria ## Footnote * Major pathway ( * Mitochondria in liver, muscle * Involves oxidation of β-carbon to release acetyl CoA

Answer 92

liver - shows in infancy hypoglycemia after long periods of fasting * ketosis due to fat brkdown to acetyl-coa * improves with eating –Mutation in GYS2 gene: autosomal recessive

Answer 93

§hyperglycemic §High HbA1c §Positive for glucose in urine §Diagnosis: Diabetes Mellitus Type II (Adult)

Answer 94

* Two molecules of phosphatidic acid linked together covalently through a molecule of glycerol * Acidic phospholipid found in inner mitochondrial membrane and in bacteria * Anti-cardiolipin antibodies have been detected in anti-phospholipid syndrome (APS), syphilis infection and in systemic lupus erythematosus •

Answer 95

spectrum of disorders in the biogenesis of peroxisomes.

Answer 96

Sildenafil ## Footnote corpus cavernosum of the penis inhibits the breakdown of cGMP(inhibits phosphodiesterase, PDE5) so that high levels of cGMP remain = high levels of vasodilation = ERECTION!

Answer 97

Øsuccinyl-CoA --\> TCA intermediate --\> OAA --\> Gluconeogenesis

Answer 98

HS, CS, DS sly syndrome: beta-gluconronidase DS: Dermatan Sulfate; HS: Heparan Sulfate; KS: Keratan Sulfate; CS: Chondroitin Sulfate

Answer 99

formation of double bonds

Answer 100

fasting, insulin intake, gng impairment = hypoglycemia * agitation, impaired judgment, combativeness •Heavy drinkers with no food deplete their glycogen stores within a few hours.

Answer 101

* Liver * From DHAP * Glycerol-P-dehydrogenase * Requires NADH * From Glycerol * Glycerol kinase

Answer 102

Increase in insulin leads to activation of Glycogen Synthase

Answer 103

1. Reductive Biosynthesis * •Fatty Acids 2. Combat Oxidative-Stress: ROS * •Reduction of Hydrogen Peroxide * •Reduction of Glutathione 3.Use of Cytochrome P450: MEOS, steroids, bile acids, vit D,detoxification of xenobiotics 4. Phagocytosis of bacteria by white cells 5. Synthesis of Nitric Oxide:NO synthase

Answer 104

A.Phosphatidylcholine (PC)

Answer 105

* Acyl CoA synthetase located in ER, outer mitochondrial membrane and peroxisomal membrane * Reaction consumes an equivalent of 2 ATP * Long chain acyl CoAs cannot cross inner mitochondrial membrane

Answer 106

Consumption of unripe fruit of Ackee-Ackee Tree (native to West Africa, introduced to Jamaica in 1776) Due to Hypoglycin A (Toxic amino acid) * •Metabolic products sequester carnitine and CoA * •Inhibits β-oxidation of fatty acids If ingested * •Sudden onset of vomiting (Within 2-6 hrs) * •Severe Hypoglycemia * •Generalized weakness, altered consciousness, and death

Answer 107

DS, KS, HS

Answer 108

* The ratio of lecithin:sphingomyelin increases sharply during weeks 31-34 of gestation * A ratio \>2 in amniotic fluid is indicative of fetal lung maturity * Surfactant biosynthesis is hormone regulated (corticosteroids, thyroxine, catecholamines) * Insufficient DPPC synthesis leads to infant respiratory distress syndrome (IRDS) * Dexamethasone is administered to mother shortly before delivery if fetal lung immaturity is suspected * A deficiency of surfactant in adult lungs causes adult version of RDS (ARDS)

Answer 109

1. Not reversal of Glycogen Synthesis 2. Cytosolic enzyme reactions 3. Primary product: Glucose 1-P from a 1-4 linkage 4. Glucose 1-P à Glucose 6-PàERà free Glucose in liver for blood glucose homeostasis via G 6-Ptase

Answer 110

•pancreatic phospholipase A2 (activated by trypsin)

Answer 111

to both proteins and lipids on the surface of red blood cells

Answer 112

stress on systems need for detoxification * infection(most common) * Excess physical activity •fava beans(favism) mothballs

Answer 113

O-linked glycoprotein

Answer 114

* Mostly derived from the 20-carbon poly-unsaturated fatty acid, Arachidonic acid (5,8,11,14-eicosatetraenoic acid) * Paracrine (Target = adjacent cell types) or autocrine (Target = same cell type) messenger molecules (“local hormones”) • •Short half-lives (10 sec – 5 mins) (exception: Prostacyclin)

Answer 115

mucolipidosis autosomal recessive - multiple acid hydrolases missing from lysosomes: secreted and found in plasma * no addition of phosphates to N-linked mannoses on enzymes destined for lysosomes large inclusion bodies in cells defect in sorting of proteins destined for lysosomes BMT = only tx option

Answer 116

Decarboxylation Reactions ## Footnote 1. PDH : E1 Pyruvate decarboxylase àCO2 2. a-KG DH:E1àCO2(TCA) 3. Transketolase: transfer of 2C units(PPP) 4. Branched chain a-ketoacid DHà CO2(A.A.)

Answer 117

* Accumulation of acyl carnitines due to CPT-2 or CACT defects * Acyl carnitines inhibit renal resorption of carnitine * Treatment * High carb/low LCFA diet * Increase MCFA content in diet * Limit physical activity * Carnitine supplements

Answer 118

* 6C -\> 5C -\> 4C * 2 CO2 * Energy: * 3NADH -\> 3x3 ATP =9ATP * 1 FADH2 -\> 1x2 ATP =2ATP * 1GTP =1ATP * Total= 12ATP/cycle

Answer 119

* Vasodilator, Bronchodilator * Stabilizes platelets, disaggregates platelets * Produced by blood vessel wall

Answer 120

1.Preferred shuttle in liver, heart and kidney 3 ATP can be generated

Answer 121

ØMain oxidative product: ØOxidizes guanosine à8-hydroxydeoxyguanosine ØMutations and carcinogenesis

Answer 122

Sugar always added to the non-reducing end via UDP-sugar

Answer 123

Precursor for nucleotide synthesis •Ribulose 5-P --\> Ribose 5-Phosphate via isomerase Ribose 5-P --\> PPRP --\> Purines and Pyrimidines (ATP, GTP, CTP, UTP, TTP)

Answer 124

glcnAc-!-P phosphotransferase --\> failure to target lysosomes and defult secretion of n-linked mannoses

Answer 125

1. insulin * MAIN + REGULATOR OF GLYCOLYSIS * high glucose = inc f (2,6)bp = increase pfk-1 = increase glycolysis 2. glucagon * low glucose = dec f (2,6)bp = dec pfk-1 = dec glycolysis = incrase GNG

Answer 126

The only significant sphingophospholipid in humans Important constituent of myelin (18% protein and 76% lipid)‏ Myelin sheath insulates and protects neuronal fibers Sphingomyelin is usually associated with the cholesterol in the membrane

Answer 127

•Cerebrosides: Ceramide + 1 or 2 sugars * •Glucose or galactose * Sulfatides: Ceramide + 1 sulfated sugar * Globosides: Ceramide + ≥3 sugars with an N-acetylated sugar * Gangliosides: Ceramide + 3 or more sugars with sialic acid (NANA)

Answer 128

normal eye - no corneal clouding increase concentration of gag in urine iduronate sulfatase deficiency hepatosplenomegaly x-linked

Answer 129

secr from panc α-cells inhib production of f(2,6)bp =pfk-1 inhib = bypass rn from f(1.6)bptase (+) = gluc prod = blood gluc homeostasis

Answer 130

* insulin * DGAT is being evaluated as a pharmacological target in the treatment of obesity

Answer 131

Most important control-point in glycolysis * rate-lim and commited irreversible under physiological condition consumes 1 ATP

Answer 132

endo-β-glucuronidase first cleaves large chains into smaller fragments each monosacc removed from nonreducing end •N- and O-sulfate groups must first be removed before exoglycosidases can act

Answer 133

liver = malate-asp shuttle - 6 atp skeletal M = g3p - 4 atp

Answer 134

Aldose Reductase

Answer 135

* (peroxisomes) * Minor pathway, no energy yield * Phytanic acid (branched)

Answer 136

Glycerol - Glycerol 3-P - Glyceraldehyde-3-P -------- GLUCOSE

Answer 137

intracellular granules in mast cells

Answer 138

* Most prevalent lysosomal storage disease * Defective glucocerebrosidase (β-glucosidase) * Gaucher cells most often accumulate in bone marrow, spleen, and liver * Leads to hepatosplenomegaly (macrophages prominent in liver and spleen), osteoporosis First disease to be treated with enzyme replacement therapy

Answer 139

ex of glyverophospholipid inositol as polar head group memb lipid, cell signal

Answer 140

protein A and B * A = usually used to synth N-linked glycoproteins in most tisuses except lactating glands * B only in lactating mamm glands - stim by prolactin * Produced by mammary gland * Under hormonal control

Answer 141

phospholipids, cholesterol, glycolipids ## Footnote −Amphipathic lipids −Both nonpolar and polar groups

Answer 142

•Forms Malate using H20 (Hydration) malate-aspartate shuttle * bring NADH into mito malate --\> pyr + NADPH (important for lipid synth) malate \<---\> oxaloacetate

Answer 143

•Niemann-Pick disease Type A and B –Autosomal recessive lysosomal storage disorders –Deficiency of acid sphingomyelinase –Type A (Less than 1% normal activity): * Death by age 2 or 3 * Hepatosplenomegaly - Sites of lipid deposit; Also CNS (ataxia, seizures) –Type B (5% or more activity) - Less severe * •Bone marrow and stem cell transplantation therapies have been useful for treating type B •Type C * disease due to the absence of sphingomyelin transporters

Answer 144

anaerobic: - when no ox path available * no mito in RBC anerobic: - ox path avail, but cell chooses lactic acid as end product * common in malignant cells glycolytic rxn are same BUT: * different isoforms inc, diff enz kinetics, diff signal paths

Answer 145

intermed of type IIB and I aero and anaero "normal m"

Answer 146

a combination of elongation and desaturation

Answer 147

−Saturated −Unsaturated (D4, D5, D6, D9) −Odd chain (minor) −Branched (minor)

Answer 148

Hurler syndrome

Answer 149

* most of the energy in your body * All of the food you eat: carbohydrates, fats, proteins all end up in some form in the TCA cycle

Answer 150

−Major storage form of energy −Membrane structure and function −Cell signaling −Insulation

Answer 151

* Mainly diet – meat * Limited synthesis in liver and kidneys from lysine and SAM * Heart & skeletal muscle cannot make carnitine but have high affinity uptake

Answer 152

−Triacylglycerols −Phospholipids −Essential FA

Answer 153

Lactic Acidosis

Answer 154

important mediators of platelet aggregation

Answer 155

ER: high mannose-type golgi: complex-type

Answer 156

ØInduction of Cyt P450: * increased rate of enzyme synthesis * results in accelerated metabolism and a decrease in pharmacologic action of co-administered drug. * e.g. St. John’s Wort with Cyclosporine (antirejection drug): –Increase in Cyclosporine metabolism by Cyto P450 --\> subtherapeutic levels of antirejection drug

Answer 157

•Lactate is exported and imported via Lactate symporters: Lactate with H+ –MCT: Monocarboxylate transporters: •Isoforms: Tumors and associated cells upregulate MCT4 isoforms:

Answer 158

type Ia Deficiency of liver G 6-Ptase * increase liver glycogen stores * severe fasting hypoglycemia * lethargy, seizures, brain dmg * Hepatomegaly * Hyperlipidemia – uses other sources of energy: fats •Lactic Acidosis and Hyperuricemia –G 6-Ptase deficiency forces glycolysis forward = increase in lactate –Lactic acid interferes with ability of kidney to filter out uric acid from blood = hyperuricemia **solved by freq meals** Type Ib: Translocase

Answer 159

* A minor pathway unless β-oxidation is defective as in MCAD deficiency * The ω-carbon is oxidized by the cytochrome P-450 system in the ER to yield dicarboxylic acids * e.g., Adipic acid - -OOCCH2CH2CH2CH2COO- •In MCAD deficiency, medium chain dicarboxylic acids (C6-C10) and their conjugates with carnitine and glycine can be detected in plasma and urine

Answer 160

UDP Glucose is used to add units of Glucose to the non-reducing end of an existing glycogen polymer a 1à4 linkages occurs in cytosol

Answer 161

Short & medium chain acyl CoAs

Answer 162

1. insulin - rtk receptor 2. irs 3. PI3 kinase 4. P: PIP2 --\> PIP3 5. AKT (PBK) - (kinase) 6. P and (-) GSK3 (glycogen synthase kinase) 7. PP1 (phosphatase) = deP glycogen synthase = ACTIVE

Answer 163

* GPAT & MGAT are activated by insulin-mediated dephosphorylation and are inhibited by AMP-activated kinase * Deficiency of AGPAT is associated with congenital generalized lipodystrophy (absence of adipose tissue and fatty liver) * AGPAT is overexpressed in cancer * DGAT expression is induced by insulin * DGAT is being evaluated as a pharmacological target in the treatment of obesity

Answer 164

Muscle:~500g (80% of body glycogen) ~1-2% of fresh weight resting muscle used as E for contaction glycogenolysis (+) by Ca2+, amp, epi **•Does NOT release glucose to blood:** **Does not have G 6-Ptase**

Answer 165

prod by S cells in duodenum response to chyme acidity func: * pancreas: secr bicarb

Answer 166

•Induced by glucose/insulin

Answer 167

blocks crosslinking either pentaglycine or direct

Answer 168

•Lysosomal storage disorders

Answer 169

* Part of an electron transport chain found in the endoplasmic reticulum. * P450 interacts with NADPH-cytochrome P450 reductase, a flavoprotein that is necessary for the transfer the reducing equivalents to Cyt P450. * Other proteins that interact with Cyt P450: cytochrome b5, NADH-cytochrome b5 reductase, and heme oxygenase.

Answer 170

•Lactate –Anerobic metabolism in Skeletal muscle, RBC etc. –Cori cycle recycles Lactate from muscle to liver for gluconeogenesis –LDH converts LactateàbloodàPyruvateàGlucose

Answer 171

* ACC converts acetyl CoA into malonyl CoA * Malonyl CoA inhibits CPT-1 * AMP (low energy) inhibits ACC and stimulates the breakdown of malonyl CoA to acetyl CoA

Answer 172

•Lens, cornea, kidney medulla, testes, leukocytes and RBC

Answer 173

Citrate (for PFK-1) ATP(high energy)

Answer 174

Membrane = polar storage = non-polar

Answer 175

(Hexose Monophosphate Shunt-HMPS)

Answer 176

•Lipoxins, Resolvins, and Protectins may be produced at lower than normal levels in chronic inflammation

Answer 177

•Liver, adipose tissue, lactating mammary gland

Answer 178

–Isocitrate DehydrogenaseàNADH +alpha-ketoglutarate –Alpha-ketoglutarate Dehyrogenaseà NADH+ Succinyl-CoA –Malate Dehydrogenaseà NADH + Oxaloacetate –Succinate DehydrogenaseàFADH2+Fumarate

Answer 179

−May augment enzyme availability after HSCT

Answer 180

when defective, leads to congenital disorder of glycosylation: type 1 (CDG-I) new synth glycoprotein in ER with N-glycan 5th step = goes to golgi: further trimming and extention to gen complex-type N-glycan when defection = type II (CDG-II)

Answer 181

cartilage, cornea, bone

Answer 182

* Alprostadil® (PGE1) – vasodilator in peripheral vascular disease. Maintains an open (Patent) Ductus Arteriosus * Misoprostol® (16,16 CH3-PGE1) – GI protective * Latanoprost® (PGF2α) – topical for glaucoma * Epoprostenol® (PGI2) – Reversal of pulmonary hypertension * Dinoprostone® (PGE2) – Induction of labor, 2nd trimester abortion

Answer 183

FADH2 --\> Complex II * Functions as part of Complex II of ETC loc: inner mito membrane Flavo protein

Answer 184

* Increased fecal excretion of TAG * Foul smelling, loose, fatty stools * Fecal incontinence

Answer 185

•Oxidative-Phosphorylation: –Every NADH - 3ATP in ETC * •3NADH produced - 9ATP –Every FADH2 - 2 ATP in ETC * •1FADH2 produced - 2ATP •Substrate level - 1GTP Total =12 ATP @ Acetyl CoA 24 ATP @ 2 Acetyl-CoA (1 Glucose)

Answer 186

## Footnote Østress hormone): opposes insulin * Degradation of TG from AdiposeàGlycerol +f.a. * Degradation of Muscle proteinàGlucogenic a.a. * Stimulation of PEP CarboxykinaseàGluconeogenesis

Answer 187

•60 percent as sweet as sucrose(4Cal/g) with one-third fewer calories(2.6 Cal/g) moisture-stabilizing action protects products from drying and maintains their initial freshness during storage

Answer 188

•Each cycle has: * •Oxidation * •Hydration * •Oxidation * •Lysis * Separate acyl CoA dehydrogenases (SCAD, MCAD, LCAD, VLCAD) * Each cycle yields 1 FADH2, 1 NADH and 1 acetyl CoA * Deficiency of MCAD causes hypoglycemia

Answer 189

Seminal Vesicles, liver,ovaries Aldose Reductase --\> Sorbitol (NADPH + H --\> NADP+) * •Sorbitol DH --\>Fructose (NAD+ --\> NADH + H) * way for the body to produce fructose from glucose without using ATP * Fructose: major E source Lens, Nerve, Kidney: * •Aldose Reductase --\> Sorbitol (NADPH + H --\> NADP+) * •Low or absent Sorbitol DH * •High [glucose] --\> high[sorbitol] --\> osmotic effects --\> swell

Answer 190

•Phase I — Cytosolic entry of acetyl CoA: * −Acetyl CoA is made in mitochondria * −Citrate shuttle is used for its transport to cytosol •Phase II — Generation of malonyl CoA: * −Activated carrier of two carbon units * −Acetyl CoA carboxylase generates malonyl CoA •Phase III — Fatty acid chain formation: * −Fatty acid synthase, a 7 enzyme complex + Acyl carrier protein (ACP) * −Palmitic acid is the end product

Answer 191

•Both the aldohexoses, glucose and galactose, can be reduced to their corresponding alcohols, sorbitol and galactitol, by aldose reductase leading to an osmotic effect in the retinaàwater retentionàblurry vision and other opthamologic complications such as retinopathy, cataracts etc.

Answer 192

* GLUT-1 * HK2 * PKM2 * LDHA * H+ Tranporters •

Answer 193

ØImportant regulatory site •Fructose 1,6-bisphosphatase inhibited by high AMP (low energy) * Stimulated by high ATP * Inhibited by F2,6bisP * Stimulated by Glucagon: * Decreases [F2,6bisP] * Increases Gluconeogenesis

Answer 194

•Allows for recycling of NADH --\> NAD+ back into glycolysis via glyceraldehye-3-P DH * G3P --\> (1,3)BPG

Answer 195

Ca2+ released from SR binds calmodulin (+) phosphorylase kinease * Activation of Glycogenolysis WITHOUT phosphorylation by PKA E for M contract

Answer 196

* Last cycle of odd-chain FA oxidation yields propionyl CoA (3C) * Propionyl CoA is metabolized to succinyl CoA via methylmalonyl CoA (needs vitamin B6) * Deficiency of mutase or of vitamin B12 causes methylmalonic aciduria * •Metabolic acidosis * •Mental retardation

Answer 197

glucogenic aa (Ala) * dec insulin = mobil aa from M = glucogenic precursors

Answer 198

* Ubiquitous * Irreversible reaction * Inhibited by its product:G-6P (feed-back inhibition)

Answer 199

* analgesic, antipyretic, but not anti-inflammatory * Does not block PG or TX

Answer 200

•Inhibitory effect of NO on platelets is mediated by NO-induced activation of soluble guanylyl cyclase: –Anti-Aggregation

Answer 201

* for muscle and brain during starvation * They can be converted to acetyl CoA * One acetoacetate = 23 ATP * One β-hydroxybutyrate = 26 ATP

Answer 202

major component of lung surfactant * biosynth = hormone regulated: corticosteriods, thyroxine, catecholamines) insufficient = IRDS, ARDS (adults)

Answer 203

* Anti-malaria medications: eg:Primaquine * Antibiotics: e.g.Sulfonamides –Treat urinary tract infections: Gantanol, Gantrisin –PCP (pneumomocysitic pneumonia) in HIV positive patients •Some Antipyretics (not acetaminophen)

Answer 204

forms pSer-IRS-1 (inactive from of insulin signal) = insulin insensitivity Metabolic syndrome

Answer 205

Part 2: Non-Oxidative, Reversible: Main products: Ribose 5-P: via Isomerase for nucleotide synthesis

Answer 206

G3P + DHAP

Answer 207

irreversible 2 atp made - substate lvl activated by f(1,6)bp inactivated by glucagon * glucagon = inc cAMP = phos PK = inactivation * inhib glycolysis under low [gluc]

Answer 208

Lung Function \>80% of the surfactant = DPPC * dipalmitoyl phosphatidylcholine * Produced by type II alveolar epithelial cells •Prevents atelectasis (collapsed lung) at end of the expiration

Answer 209

Glycogen Storage Disease Type 1a - most common auto recessive - missing liver G6Ptase symptoms: * hypoglycemia, hepato-renal-megaly(enlarg), hyperlipidemia, hyperuricemia (high uric acid) tx: * no fasting!

Answer 210

Deficiency of carnitine or defects in CPT-1, CPT-2 or CACT

Answer 211

–nonmetabolizable derivative of glucose preferentially taken up by tumor cells •Can follow tumor treatment response using FDG-PET: * Fluorodeoxyglucose-positron emission tomography

Answer 212

type II - acid maltase deficiency Lysosomal acid alpha-1,4-glucosidase deficiency (GAA) * •Cannot degrade lysosomal glycogen = accumulation * •Only Glycogen Storage disease that is Lysosomal Storage disease * Autosomal recessive - gene therapy (myozyme) * Cardiomegaly (Pompe affects “the pump”) - M weakness

Answer 213

1. HMPS: 2NADPH @ Glucose 6-P * •\*Glucose 6-PDH * •6-P Gluconate DH 2. Malic Enzyme: (cytosolic Malate DH) NADPH: Important for hepatic lipid synthesis

Answer 214

* ENDPRODUCT: lactate * Energy production: 2ATP * No net production of NADH

Answer 215

•Lethal at a young age

Answer 216

ØManganese SOD (Mn SOD)- mitochondrial enzyme ØSOD1:Copper-Zinc SOD(CuZnSOD) – mainly cytoplasmic but also found in lysosomes, peroxisomes,nucleus ØDeficiencyàprogressive neurodegenerative disorder, Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s Disease) ØALS: most have single pt-mutation (1a.a.) ØExtracellular SOD(ECSOD)-uses Cu,Zn

Answer 217

Cleaves high-energy Succinyl-CoA --\> GTP (interconvert with ATP), CoA Substrate–level phosphorylation

Answer 218

* Three fatty acids attached by ester linkage to a backbone of glycerol * Removal of FA requires hydrolysis by lipases

Answer 219

targets lipoic acid ## Footnote ØInhibits Lipoic Acid containing enzymes * PDH * a-Ketoglutarate DH (TCA cycle) * branched-chain a-Ketoglutarate DH (amino acid metabolism) ØLeads to increase in Pyruvateà Lactate (Lactic Acidosis) ØAffects brain: neurological disturbances and death

Answer 220

ØRepression(Inhibition) of Cyto P450: * Reduces the metabolism of co-administered drug by inhibition of cytochrome P-450 activity. * Results in higher levels of drugàtoxic effects * e.g. grapefruit with statins: –High levels of statinsà rhabdomyolysis

Answer 221

1.Interconversion of 3,4,5,6,7 sugars: ØTransaldolase ØTransketolase: Fructose 6-P Glyceraldehyde 3-P for glycolysis, gluconeogenesis, etc

Answer 222

G_s protein ## Footnote epi (M), glucagon (L) --\>G_s--\> protein kinase A (+) ---\> phosphorylase kinase (+) ---\> phosphoylase a ----\> glycogen to g1p and n-1 glycogen

Answer 223

B.Degradation of gangliosides

Answer 224

Glycogen Synthase Deficiency (very rare) M * beings early childhood * M pain, weakness, syncope following mod physical activity * arrhythmia - impairs heart ab to pump blood -- –Mutation in GYS1 gene : autosomal recessive

Answer 225

ØNO-cGMP cascade is involved in learning and memory through the maintenance of long-term potentiation in the hippocampus: Helps convert short term memory to long-term memory

Answer 226

•important in smooth muscle contraction and immediate hypersensitivity reactions, particularly in asthma

Answer 227

duodenum increase SA of lipids bile salts + peristalsis * lipid particles = smaller, prevented from coalescing

Answer 228

main pathway that metabolizes carbohydrates WITHOUT mitochondria 2 ATP via SUBSTRATE-LEVEL

Answer 229

(Phos/Dephos) of Glycogen Synthase via Insulin Two forms: –Active (dephosphorylated): Glycogen Synthase a or I –Inactive (phosphorylated) Glycogen Synthase b or D

Answer 230

Hormonally Regulated •FA released from TAG in adipocytes by Hormone-sensitive lipase (HSL) * •Epinephrine and glucagon activate HSL * •Insulin inhibits HSL * Released FA are transported by serum albumin to liver and muscle * Glycerol is used for gluconeogenesis by the liver

Answer 231

TAG ## Footnote * Glycerol esterified with three FA, added one at a time * Usually contain a saturated FA on C1 and an unsaturated FA on C2 with a variable FA on C3 * Stored mostly in adipose tissue but also as lipoproteins * Precursors are glycerol 3-P and fatty acyl CoA

Answer 232

* Adipose tissue * Only from DHAP * Glycerol kinase is absent in adipose tissue

Answer 233

−increase with chain length −decrease with unsaturation

Answer 234

Similar to prostaglandins but have instead a 6-membered ring containing oxygen * Abbreviated TX * Role in blood clotting via platelet aggregation

Answer 235

Ala, Gln –From hydrolysis of tissue proteins –Major precursor during a long term fast

Answer 236

triacylglycerols

Answer 237

* Palmitate is first activated to palmitoyl CoA * Elongation occurs in smooth ER and in mitochondria * Similar to FA synthesis * Elongase uses either malonyl CoA (SER) or acetyl CoA (mitochondria) as the 2-carbon donor * NADPH supplies the reducing equivalents

Answer 238

ØNADH production increases --\> lactate.

Answer 239

Glucokinase * High Km for Glucose(~10mM) * Functions at high [Glucose] after high-carb ingestion * High Vmax * Removes glucose quickly after being delivered to liver via portal vein * Minimizes chance for hyperglycemia Hexokinase * Low Km (high affinity)(~0.1mM) * Activity under low [glucose] * Low Vmax * [G6-P] is formed only as needed

Answer 240

type V - •Skeletal muscle phosphorylase deficiency(myophosphorylase) normal liver enz Autosomal recessive - child/adult onset No rise in blood lactic after exercise Myoglobinemia and myoglobinuria Benign condition-normal mental development High level of muscle glycogen-normal structure

Answer 241

(most fats) cannot make glucose ## Footnote (but do provide ATP and NADH for its synthesis) Acetyl-CoA (end product of fat metabolism) is NOT a gluconeogenic precursor

Answer 242

under decreased O2 conditions (hypoxia) anaerob metab MI, pulm embolism, shock

Answer 243

acts on phosphatidyl-inositol, releasing arachidonic acid (procursor to prostaglandins) panc secre = rich with phospholipase a2 proenz = activ by trypsin, requires bile salts for activity inhib by glucocorticods (cortisol)

Answer 244

\*Sucrose Glucose Mannose Sorbitol

Answer 245

ØIncrease in pyruvate --\> lactate via LDH: abnormal lactate buildup: * severe lethargy, * poor feeding, tachypnea (increase in breathing) especially during times of illness, stress, or high ØLeads to a loss of ATP * Loss of NADH from PDHC --\>loss of 3ATP@NADH * loss of ATP from TCA (Acetyl-CoA not feeding into TCA cycle) ØCauses neurological problems

Answer 246

•inhibitor of TX synthase as well as TX receptor activity

Answer 247

salts = deprotonated bile acids (pka around 2-4) more effective detergents than acids

Answer 248

Phospholipids bilayer of cell membranes * Decrease lipid mobility * Polyunsaturated fatty acids most prone to ROS * Oxidation of LDL(lipoprotein)àCVD

Answer 249

OH group on ser/thr NH2 group on Asn - more abundant

Answer 250

first is G-6-PD deficiency in HMPS

Answer 251

•pancreatic lipase, phospholipase A2 and cholesterol esterase

Answer 252

•Orlistat (Xenical®, Alli®) −Anti-obesity drug (OTC) −Inhibits pancreatic and gastric lipase •Olestra (Olean®) −6-8 FA attached to sucrose −Non-digestible −Pringles® with olestra came with the warning “Wear dark pants”

Answer 253

•Phase I –Parent drug converted to a polar metabolite by addition of a functional group •e.g. OH by CYP –If drug is polar enough, it is excreted. Or continue to phase II. •Phase II –Increased MW due to conjugation e.g. glucuronate, acetylation

Answer 254

1.Substrate-level: * Energy needed to form ATP comes from a high-energy substrate * Ex: Phosphoenolpyruvate (PEP) -\> Pyruvate + ATP * anaerobic 2. Oxidative-Phosphorylation (Ox-Phos): * Energy needed to form ATP comes from the Electron Transport Chain in mitochondria (aerobic)

Answer 255

HFI causes buildup of fructose -----\> hypoglycemia and hyperuricemia fructosuria = defic in FK = fruc removed in urine

Answer 256

−Does not cross blood-brain barrier (intrathecal administration has been proposed) −May benefit patients with all forms of disease

Answer 257

deficiency of phytanyl CoA hydroxylase prevents α-oxidation of phytanic acid cerebellar ataxia, peripheral polyneuropathy, retinitis pigmentosa, and hearing loss

Answer 258

Zetia® inhibits absorption of cholesterol by interfering with NPC1-L1

Answer 259

Asn-linked glycoprotein made in the ER

Answer 260

Our City Is Kept Safe and Sound From Malice Oxaloacetate Citrate Isocitrate α-Ketoglutarate Succinyl-CoA Succinate Fumarate Malate

Answer 261

* CPT-1 in OMM (forward reaction) * CPT-2 in IMM (reverse reaction)

Answer 262

Reoxidation of NADH--\>NAD+ in Lactate Synthesis

Answer 263

Normal * A1C - about 5 * fasting glucose = 99 or below Pre * A1C - about 5.7-6.4 * fasting glucose = 100-125 DM * A1C - 6.5 and above * fasting glucose = 126 or above

Answer 264

•Prostaglandins: Cyclopentane ring • •Thromboxanes: six-membered oxygen-containing ring • •Leukotrienes: 3 conjugated double bonds + one unconjugated • •Hydroxyeicosatetraenoic acids (HETEs):

Answer 265

* Degradation of FA occurs in two phases * Phase I: Transport of FA into mitochondria * •Activation of FA to Acyl CoA * •Transfer of FA to Carnitine * •Carnitine shuttle •Phase II: β-Oxidation of FA * •Repeated cycles of 2-carbon removal * •Dehydrogenation * •Hydration * •Dehydrogenation * •Thiolysis

Answer 266

β-amyloid formation and in thrombosis

Answer 267

Transketolase: Needs thiamine for activity ØUsed to measure thiamine levels in blood ØDeficiencyàberiberiàheart failure

Answer 268

20-30 molecules FA cholesterol MAG lysolecithin vitamins A, D, E, K

Answer 269

base exchange

Answer 270

•Increase: –Expression of Glu Transporters •Decrease: –Proper formation of Complex IV (Cyt c Oxidase) –Decrease in ETC

Answer 271

•fats and oils float

Answer 272

* Six classes of GAG based on the repeating unit (n = 100s to 1000s) * Amino sugars may be Sulfated (on C4, C6 or on non-acetylated N) * Five of the six classes of GAG are covalently attached to proteins (exception is hyaluronic acid)

Answer 273

–Too high: hyperglycemia:diabetes –Too low: hypoglycemia: confusion, coma, death

Answer 274

•places the initial double bond between C9 and C10; additional double bonds can then be introduced

Answer 275

duodenum - pancreatic lipase

Answer 276

* Releases Glucose via G 6-Ptase * Regulated by insulin/glucagon, blood glucose, epinephrine * Usually lasts 16-18hrs fasting

Answer 277

4 ATP/GTP –Glycolysis: 2 net ATP –TCA:2 GTP (succinate synthatase)

Answer 278

•Increases: –Glycolytic enzyme gene expression –GLUT 1 and 3 –LDH –MCT4 •Decreases: –PDH –Number of mitochondria

Answer 279

ER ## Footnote * Minor pathway * Normally SCFA substrates ( * Makes dicarboxylic acids

Answer 280

back to Hepatic Glucose (Cori Cycle) and glucose released to blood

Answer 281

Primary constituents of cell membranes Two fatty acids form ester linkages with the first and second hydroxyl groups of L-glycerol-3-phosphate Head group is charged at physiological pH Unsaturated fatty acids are commonly found connected to C2

Answer 282

* FA synthase complex contains 7 different enzyme activities * The addition of each 2-carbon unit requires four steps: * Condensation * Reduction * Dehydration * Reduction * The end product of FA synthase is the 16C FA, palmitic acid * FA are synthesized from ω-end to α-end

Answer 283

fast twitch - contracts faster fatigues easy anaerobic

Answer 284

FA synthesis is regulated at 3 levels * ATP:Citrate lyase * Acetyl CoA carboxylase * Fatty acid synthase

Answer 285

•(non-classical galactosemia) Rare autosomal recessive disorder * semia and galactosuria * No Gal 1-P accumulation in tissues * Galactitol accumulation * Can lead to cataract formation

Answer 286

prostaglandin, arachidonic acid

Answer 287

•Cannot reform Pyruvate from Acetyl-CoA to synthesize glucose for gluconeogenesis

Answer 288

* 95% metabolized in liver * Oxidation of Ethanol--\> large [NADH]

Answer 289

normal = 70/110 post meal * under 120 1-2hrs after meal * most = \<100 by 2 hours after meal hyperglycemic fasting blood sugar * \>126

Answer 290

GAGs repel due to negative charges, surr by water shell contraction causes water between gag to squeeze out - return to extended/hydrated state when released

Answer 291

glyceraldehyde ---(aldehyde DH)---\> glycerol ---(glycerol kinase)---\> g3p **glycerol kinase (not in adipose)** g3p = backbone for TG (fats)

Answer 292

* Vasoconstrictor * Bronchoconstrictor * Pathogenic in asthma * Contracts uterine smooth muscle, active in labor and delivery

Answer 293

* Aspirin (but not other NSAIDs) promotes the synthesis of AT-Lipoxins and AT-Resolvins (not Protectins) * Conversion of DHA and EPA, into Resolvins and Protectins may account at least part of the reported nutritional benefits of ω-3 fatty acids, * reported 45% decrease in sudden death of cardiovascular disease patients taking close to 1g of ω-3 fatty acids/day (11,000 patients enrolled) * Aspirin combined with ω-3 fatty acid supplements may have synergistic effects but a careful study has not been carried out * Synthetic Lipoxins, Resolvins, and Protectins have promise for treatment of many inflammatory disorders such as asthma, cardiovascular disease, arthritis, etc.

Answer 294

mito matrix EXCEPTION: succinate DH

Answer 295

PGE2 * Vasodilator, bronchodilator * Cytoprotective in GI tract * Proinflammatory: Pain, swelling, redness * Contracts uterine smooth muscle, active in labor and delivery

Answer 296

activation of oncogene ## Footnote Upregulation of: * GLUT-1 * HK2 (Hexokinase isoform) * PKM2 (Pyruvate Kinase isoform) * LDHA (L4-Skeletal Muscle)

Answer 297

Andersen disease •Deficiency of glycogen branching enzyme: (glucosyl 4:6 transferase) Amylopectinosis * dec in amylopectin-branched glycogen = insolub glycogen * abnormal glygen structure - long outer branches * Failure to thrive: growth and mental development declines * Hepatosplenomegaly * Progressive cirrhosis * Muscle hypotonia * Death typically occurs by five years of age.

Answer 298

* NADH formed --\> 3ATP * Rate-limiting rx: exergonic * Importance of a-ketoglutarate * Interconverts with Glutamate via Glu DH: * source of Glu or Glu = source of a-KG for TCA

Answer 299

Essential Fructosuria : Benign •Fructose cannot be metabolized * eliminated in urine * Detected as a reducing sugar

Answer 300

Answer: * Carbohydrates (sugar, breads, pastas, fruit, soda) raise insulin levels * Insulin's job is to move sugar and fat out of the blood * It does this mainly by opening up fat cells for storage * It also decreases fat break down * Increased insulin means increased storage and less fat burning * Glucose by itself promotes the expression of ATP:citrate lyase and acetyl CoA carboxylase * The net result is that carbohydrate is efficiently converted to stored fat

Answer 301

Forms NADH, OAA endergonic * driven forward by low [OAA] due to use in citrate synthase rxn

Answer 302

•Non-Insulin dependent uptake : GLUT 5 transporter

Answer 303

Thiamine deficiency ## Footnote * ataxia,ocular abnormalities,mental disorder characterized by disproportionate memory loss and confusion * Often associated with alcoholism- due to poor nutrition

Answer 304

glycerate kinase and g-3-pdh = reversible rxns in glycolysis IRREVERSIBLE : -G

Answer 305

increases after chronic alcohol consumption. MEOS pathway requires the CYP2E1 enzyme, part of the cytochrome P450 family of enzymes

Answer 306

Biotin-Dependent Biotin: water soluble vitamin – functions as a CO2 carrier for several important reactions including: * Acetyl-CoA carboxylase * Pyruvate carboxylase * Propionyl CoA carboxylase

Answer 307

Carboxylic acids with hydrocarbon chains containing between 4 to 36 carbons Almost all natural fatty acids have an even number of carbons Most natural fatty acids are unbranched

Answer 308

* CPT-2 defects (muscle) * Cardiomyopathy, rhabdomyolysis

Answer 309

prod by I-cells n duodenum and jejunum func: * stomach: decrease gastic motility * pancrease: secr panc enz * gallbladder: secr bile

Answer 310

* Gene expression * Insulin, feeding (↑) * PUFA, fasting (↓)

Answer 311

•Increased lipolysis leads to increased delivery of FA to liver * •Fasting * •Type I Diabetes * Increased FA β-oxidation produces acetyl CoA * Excess acetyl CoA in liver mitochondria leads to production of ketone bodies

Answer 312

* FA synthase binds one acetyl unit and one malonyl unit * A 2-carbon unit is transferred from malonyl unit to acetyl unit to form a 4-carbon unit * The oxygen is replaced by hydrogens * This process is repeated using new malonyl units a total of 7 times

Answer 313

inhibitor of pancreatic lipase weight loss drug

Answer 314

F6P --\> Glucokinase regulatory protein (GKRP)--(+)--\> bind Glucokinase --\> nucleus When [glucose]increases --\> GKRP releases GK --\> P glucose --\>preventing hyperglycemia **GK only active under higher [glucose]**

Answer 315

quickly mobilized metab anaerob (glycolysis) maintain blood gluc homeostasis (liver) •Does not create an osmotic problem for cell as would glucose monomers

Answer 316

---\> 2,3 BPG via bpg mutase regulated Hb binding of O2

Answer 317

ØCoASH released ØImportance of Citrate: vShuttled to cytosolàAcetyl-CoA + OAA * Acetyl-CoA used to make fat * Citrate activates main fat synthesizing enzyme in cytosol • ØTake Away Point: SUGARS ARE FATTENING!!!!!!!

Answer 318

•lack of charged carboxylate group

Answer 319

triacylglycerols, cholesterol esters ## Footnote −Neutral lipids −Intracellular storage ØLipid droplets in adipose

Answer 320

all goes to liver ## Footnote atp -\> adp-\> amp-\> uric acid (amp deaminase)-\> gout uric acid blocks NO synthase = dec NO = dec in vasodil = **htn!!**

Answer 321

metabolic acidosis --\> hyperventilation (respiratory compensation)

Answer 322

Second most common cause of enzyme deficiency-related hemolytic anemia ## Footnote * Increase in 2,3BPG * Lower-than normal Oxygen affinity:Hb in the T-state decrease in ATP production in glycolysis --\> cannot maintain proper RBC membranes (Na/K ATPase) --\> hemolysis

Answer 323

* ENDPRODUCT: pyruvate * Pyruvate --\> Acetyl-CoA --\> TCA (energy)

Answer 324

The only significant sphingophospholipid in humans Important constituent of myelin (18% protein and 76% lipid)‏ Myelin sheath insulates and protects neuronal fibers

Answer 325

blocks attachment of GAG to peptide

Answer 326

cell-cell adhesion (glycan binding proteins - GBP) cell signally receptors for virusbac gene reg: Ts factors are O-glycosylated immune response (many antigens = glycans) protein sorting (lyso target by glycan tagging)

Answer 327

* Choline is an essential nutrient * When choline levels are low * PE can be converted to PC by transferring methyl groups from S-adenosyl methionine (SAM) **Phospholipid synthesis is ubiquitous**

Answer 328

PDHC Deficiency

Answer 329

Activated during well fed state Inhibited during fasting state

Answer 330

Glycerol 3-P Shuttle Malate-Aspartate Shuttle

Answer 331

Ø(low blood glucose): opposes insulin * decreases synthesis of F 2,6-bisPà * decrease in glycolysis (PFK-1) * increase in gluconeogenesis (F1,6-bisPtase)

Answer 332

Ether linked saturated FA at C1 Acetyl ester at C2 Phosphocholine at C3 Activates inflammatory cells Mediates hypersensitivity, acute inflammatory and anaphylactic reactions Synthesis and release of PAF → platelet aggregation and release of serotonin from platelets

Answer 333

ØLactate --\> Pyruvate --\> Glucose ØAlanine --\> Pyruvate --\> Glucose * Glutamine in kidney and small intestines ØGlycerol (from fats) --\> Glyceraldehyde-3P --\> Glucose

Answer 334

type IIb : white fibers

Answer 335

* LT are more stable than PG (half life = hours) * The C, D and E class of LT together are termed slow reacting substance of anaphylaxis (SRS-A) * Mediators of immediate hypersensitivity * By blocking PG synthesis, aspirin can increase the conversion of arachidonate to LT and potentiate hypersensitivity

Answer 336

HMPS Fructose a6-P and Glyceraldehyde 3-P can be formed without the use of ATP

Answer 337

Triacylglycerol

Answer 338

1. NADPH: used for many synthetic pathways: Lipids; Cytochrome P450 reactions 2. Ribose 5-phosphate: for nucleotide synthesis 3. Mechanism for metabolism of 5 carbon sugars and interrelationship between carbohydrate pathways

Answer 339

•celecoxib anti-inflammatory •Do not block TX production

Answer 340

exogenous or diet-derived lipids * ppl * apolipoprotein B48 (from aa) * TAG * cholesteryl ester deliver to muscle, adipose and liver via lymph sys

Answer 341

Defects in peroxins ## Footnote •decreased cerebral myelination and a loss of hearing and vision

Answer 342

Nomenclature is similar to LT, PG, TX, and HETE: * Lipoxin = LX * Resolvin = Rv * Protectin = P * Capital letter designation of different forms * Subscript = number of ‘non-ring’double bonds for LX * AT =‘Aspirin-triggered’= different stereochemistry • Synthesized from: * Arachadonic acid (C20:4, ω-6) - Lipoxins * Eicosapentanoic acid (EPA, C20:5, ω-3) - E series Resolvins * Docosahexanoic acid (DHA, C22:6, ω-3) - D series Resolvins and Protectins

Answer 343

•Phosphorylation of ACC promotes its depolymerization to inactive dimer

Answer 344

–transfers Alanine to Liver for gluconeogenesis: –Ala - blood - Pyruvate --- Glucose

Answer 345

dec [NADPH] = inc ROS RBC lipids memb ox =hemolysis = hemolytic anemia = jaundice dmged RBCS removed by macrophages in spleen and liver Hb in RBC ox = disulfide bonds with metHB --\> ppt (Heinz bodies)

Answer 346

glut 4 increased under insulin to txp gluc out of blood and into tissues

Answer 347

•Activated under well fed state by Glucose 6-Phosphate * prod hexokinase/glucokinease * in M and liver g6p --\> g1p

Answer 348

Type III - ØDebranching enzyme deficiency ØAccumulation of an abnormally structured glycogen having very short outer chains symptoms: * hepatomegaly, fasting hypoglycemia, myopathy tx: freq high carb meals with constarch supplements * high protein diet also effective = drives gng ØAutosomal recessive: * 1:100,000 General population * 1:5,400 North African Jews (1:35 carriers N.African Jews)

Answer 349

Liver:~100g •10% of fresh weight liver:\

Answer 350

Ø(high blood glucose):opposes glucagon * increases [F 2,6-bisP]à increase in glycolysis (PFK-1) * decrease in gluconeogenesis (F1,6-bisPtase)

Answer 351

•Always in consensus sequence ---Asn-X-Ser/Thr--- Where X = any amino acid except Pro −Antibodies (IgG) −Glycoprotein IIb/IIIa on platelets (aggregation and blood clotting) −gp120 (HIV)

Answer 352

* NADPH Oxidase deficiency * Not able to form ROS in Phagolysosome to kill bacteria * Increase in granulomas (nodules of inflammation) that have sequestered bacteria and were not destroyed = Severe persistent infections

Answer 353

•First step catalyzed by acyl CoA oxidase, e- go to oxygen directly

Answer 354

a 1,6 linkages @ 6-8 residues increase # sites for synth/degrad increase # non-reducing ends avvail for degradation when needed increases solubility –Amylopectin has branches –Amylose: straight chain: less soluble

Answer 355

starts in mouth - lingual lipase stomach - gastic lipase lipase characteritics: * optimum pH 4-6 * act on short/medium chains * directly absored into bloodstream from stomach * sig in infacts, adult CF pts with pancretic insuff

Answer 356

Bifunctional ## Footnote A.4:4 Transferase: Transfers 3 glucose units to another branch to elongate (all alpha 1,4) B. 1:6 Glucosidase: Single glucose left at branch site of a1,6 hydrolyzed results in free glucose

Answer 357

Fe2+ + H2O2 = .OH + OH– + Fe3+ ## Footnote Next, the O2.- reduces the ferrous ion (Fe3+) to produce Fe2+ and allows that the previous reaction can continue: O2.- + Fe3+ = O2 + Fe2+

Answer 358

cycles of beta-ox steps interspersed by rxns cat by an isomerase and a reductase Need additional enzymes: * •NADPH-dependent enoyl CoA reductase * •Enoyl CoA isomerase * •Fewer ATP than saturated FA *

Answer 359

liver TG and fat synthesis

Answer 360

Gal b1--\>4 Glu UDP-Galactose: Activated Form

Answer 361

liver = MAIN! •Kidney cortex: * During periods of severe hypoglycemia during liver failure •Small Intestines: under high protein/fasting/renal failure

Answer 362

prim in plant tissue potential therapeutic target in the treatment of Alzheimer Disease and stroke

Answer 363

* Odd-chain FA are synthesized when FAS is initiated with propionyl CoA instead of acetyl CoA * Small amounts (\<1%) of C15 and C17 FA in plasma lipids * Branched-chain FA are synthesized by initiating FAS with CoA derivatives of branched-chain keto acids (products of Leu, Ileu and Val) * Not very important in human metabolism

Answer 364

ABCD: * Andersen Type IV: Branching * Cori Type III: Debranching

Answer 365

–Triglycerides (stored in Adipose) triglycerides = 3 FA + glycerol

Answer 366

* Seen in homozygotes: need a reduction of \> 50% of activity to see clinical symptoms * Gal 1-P increases in tissues and Gal seen in blood and urine * Mental retardation: need immediate treatment with infants * Newborns ingest up to 1g galactose/day in milk * Liver and kidney damage and cataracts * Part of Newborn Screening Panel NYS

Answer 367

via bile salts ## Footnote •~5% of bile salts excreted in feces

Answer 368

Pyruvate carboxylase

Answer 369

Hereditary Fructose Intolerance (HFI) - like poisoning •Seen after a baby starts eating food/formula inc [F1P] in blood = Decrease Pi and ATP production = increase AMP = dec gng * Hypoglycemia, Hyperuricemia * Hepatic failure and death •Therapy: Remove fructose and sucrose from diet

Answer 370

* Mediators of active resolution of inflammation, a concept that has replaced the idea of passive resolution * Synthesis of AT-Lipoxins and Resolvins triggered by aspirin modification of COX2 * Synthesis involves some enzymes common to the synthesis of PGs, LTs, and HETEs, including cyclooxygenase and lipoxygenases * They provide additional mechanistic insight into the potent anti-inflammatory actions and benefits of aspirin * Resolvins and Protectins may help explain the clinically documented benefits of ω-3 fatty acids like docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)

Answer 371

**Increased NADH/NAD+ ratio** * (-) gng (removal of precursors) * (-) F.A. oxidation cycle --\> Fatty liver since FA (supposed to be ox in liver) stays there * increase in TG = Hyperlipidemia * (-) TCA --\>Acetyl-CoA --\> Ketone Bodies --\>Acidosis * –Increase in Lactic Acid --\>Acidosis * Increase in acidity can --\> decrease in uric acid excretion --\> * Gout (Deposition of uric acid in joints)

Answer 372

(GOD He's Massive) Gout Obesity Dyslipidemia Htn Metabolic syndrome (pSER-IRS-1)

Answer 373

•Cis unsaturation causes a kink in fatty acid chain * more cis = more kinks •Saturated fat and trans fat are risk factors for coronary artery disease

Answer 374

. Because humans cannot synthesize n-6 (ω-6) and n-3 (ω-3) FA

Answer 375

* Sphingomyelinase removes phosphoryl-choline to leave ceramide * Ceramidase cleaves ceramide to FA and sphingosine

Answer 376

α-iduronidase deficiency hernia, **corneal clouding,** coarse features, claw hand

Answer 377

* Hypoketotic hypoglycemia * Incidence * 1 in 12000 * Leads to a deficiency of both ATP and acetyl CoA * Both ATP and acetyl CoA needed for gluconeogenesis * •Acetyl CoA is the obligatory allosteric activator of PC * •Low acetyl CoA = low ketone bodies * C8, C10 acyl carnitines accumulate in blood and urine * ω-oxidation of MCFA produces dicarboxylic acids

Answer 378

* With the exception of the red blood cell, prostaglandins are produced and released by nearly all mammalian cells and tissues * PG effects vary from one target cell population to another due to multiple GPCR and effector enzymes * Because of their very short half-lives, all but prostacyclin (PGI2 = circulating hormone) act over short distances cell to cell (paracrine) * PG not stored in cells but instead synthesized and released immediately

Answer 379

Type II GSD (Pompe Disease)

Answer 380

decrease in precursors of GNG

Answer 381

−Acetyl CoA −NADPH −ATP

Answer 382

GPCR •LTB4 acts via BLT receptors which couple to Gi (↓ cAMP) * •Brochoconstriction * •Chemotaxis of neutrophils •LTC4 and LTD4 act via CysLT receptors which couple to Gq (↑ Ca2+) * •Degranulation of mast cells * •Bronchoconstriction •LTE4 - CysLT receptor * •Smooth muscle contraction

Answer 383

* PIP2 is the source of two second messenger molecules in Gq signaling * PI is also an intermediate in PI 3-kinase signaling by insulin * C2 of PI is esterified with arachidonic acid (20:4) which is the precursor of eicosanoids

Answer 384

•When the polar group is a sugar alcohol * •Phosphatidic acid is activated to CDP-DAG * •Glycerol or inositol added to CDP-DAG * •Phosphatidylglycerol (PG) or Phosphatidylinositol (PI) •When the polar group is a nitrogenous base * •Choline or ethanolamine is activated by CDP * •Then added to DAG * PC or PE

Answer 385

instead of 36/38 ATP, ca cells only get 2 atp from gluc --\> lactate needs 19 mol gluc to produce equivalent quant

Answer 386

joint and ocular fluids, cartilage

Answer 387

(activation of Akt oncogene) ## Footnote Upregulation of : * GLUT-1 * HK2

Answer 388

* Gluconeogenesis uses 7/10 glycolytic reactions in the reverse direction * 3/10 reactions are irreversible and need to be “bypassed” with different enzymes * Gluconeogenesis is irreversible

Answer 389

Tissues with low mitochondria, will convert pyruvate to lactate normally Tissues that are under hypoxia, will not be able to reconvert lactate to pyruvate * lactate accumulates and can be sent via the blood to the liver (Cori Cycle) for gluconeogenesis

Answer 390

* F2,6bisP (for PFK-1) * F1,6bisP (for PK) * AMP(low energy)

Answer 391

* VLCFA (\>C20) * Less energy than in mitochondria

Answer 392

* Monosaccharides sequentially added to OH groups of Ser or Thr (sometimes HyL as in Collagen) * No consensus sequence but Ser/Thr near or adjacent to Pro * Each activated sugar added by a specific glycosyltransferase in the Golgi apparatus/Nucleus/Plasma membrane

Answer 393

1. g6p txp to ER 2. dephos by g6ptase in ER memb 3. gluc txp out of ER to cytosol 4. gluc txp out of liver to blod as free blood gluc by GLUT2

Answer 394

Inflammed Tissue * PGE2 * Pain, Swelling, Redness Blood Vessel Wall * Prostacyclin * Antithrombotic Kidney, Arterioles * PGE2, Prostacyclin * Antihypertensive

Answer 395

flow of bile from gallbladder to the intestines is blocked usually due to gallstones result = jaundice

Answer 396

phosphoglucomutase ER translocase --\> g6p --\> glucose --\> free blood gluc --\> out to cytosol via glut7 --\> into bllod via glut2

Answer 397

1. E * atp = negative - E abundance * adp = positive - low E signal 2. citrate * negative - E abundance 3. F (2,6) BP * positive

Answer 398

•PG**_A_**, PG**_D_**, PG**_E_**, PGF, PGG, PGH, PGI The functional groups present at 9 and 11 •PGE _{1, 2}or ₃ The subscript refers to the number of double bonds present in the linear hydrocarbon chain •The subscript a refers to the configuration of the 9–OH group (projects down from the plane of the ring)

Answer 399

•Presentation: hemolytic anemia, jaundice

Answer 400

interferes with the absorption of fat-soluble vitamins (A, D, E and K)

Answer 401

PART 1 : Oxidative * makes NADPH •Glucose 6-P --\> Ribulose 5-P + 2 NADPH –Irreversible steps that produce NADPH: 1. Glucose 6-DH(G6PD)\*+ NADPH 2. 6-Phosphogluconolactone hydrolase + NADPH

Answer 402

NO! Patient’s with GSD Type 1a cannot RELEASE glucose due to a deficiency in Glucose 6-Ptase. They can metabolize glucose when ingested.

Answer 403

* End product of aerobic glycolysis in cytosol (pyruvate kinase) * Transported into mitochondria for oxidative metabolism in TCA cycle via pyruvate transporter * Major source of Acetyl-CoA for TCA cycle from carbohydrates

Answer 404

glycerol ## Footnote (Adipocytes lack glycerol kinase, so glycerol transported to liver)

Answer 405

operates in skeletal muscle and brain MAX 2 ATP gen from each NADH produced in glycolysis

Answer 406

ØEndothelium-derived relaxing factor: Relaxes smooth muscle:dilator ØNeurotransmitter in central and peripheral nervous system ØMacrophage bactericidal ØInhibitor of platelet aggregation

Answer 407

slow twitch - contracts slow low fatigue - endurance aero

Answer 408

* CYP1, 2, and 3 families, are responsible for the biotransformation of most foreign substances including 70–80% of all drugs in clinical use * Active in many tissues: * e.g. liver, kidney, intestines

Answer 409

fats main fuel for liver and E for gng = 6 atp •C16 --\> ~130ATP * Fatty acid oxidation --\> Acetyl-CoA --\> TCA --\> ETC --\> ATP •Fats --\> Acetyl-CoA * allosteric activator of pyruvate carboxylase --\> glucose

Answer 410

endergonic: 2 atp used exergonic: 4 atp made, 2 nadh made NET: * glucose --\> 2 pyr * 2 ADP --\> 2 atp * 2 NAD+ --\> 2 NADH

Answer 411

Pyruvate Carboxylase: * (+) acetyl-CoA * (-) ADP F1,6 bisPtase: * (+) citrate * (-) F(2,6)BP, AMP

Exam 2 Flashcards

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