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256 Cards in this Set
- Front
- Back
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Before they can enter into the cell, starches and other oligosaccharides must be broken down into... |
monosaccharides first |
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The function of salivary amylase is... |
breaking doen internal bonds, does this through brief contact |
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Salivary amylase is limited in that it cannot... |
break down alpha-1,6glucosides or alpha-1,4 branch points |
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The stomach does not have any... |
enzymes for carb digestion |
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Most carb digestion occurs in... |
the small intestine in 2 major components 1. Lumen 2. Enterocyte |
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In the lumen of the small intestine is the enzyme... |
pancreatic amylase |
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Pancreatic amylase produces... |
alpha limit dextrins |
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alpha limit dextrins have... |
8 glucose units with 1 or more alpha-1,6 branch points which will he digested to maltose, maltotriose and glucose |
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Only monosaccharides can be... |
absorbed into intestinal epithelial cells |
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The final hydrolysis of di and oligo saccharides to monosaccharides occurs... |
on the surface of small intestinal epith. cells |
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di/oligo/polysacs not hydrolized in the small intestine are... |
cannot be absorbed by epith cells and will travel to lower small intestine or large intestine |
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bacterial digestion of tough carbohydrates in large intestine results in.. |
CO2, methane, hydrogen gases and short chain fatty acids |
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The bacterial products of large intestine cause these symptoms: |
fluid secretion, increased motility, cramps and gasing |
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When lactase if deficient lactose will... |
pass to colon > GI tract distress (cramping, bloating from CO2, CH4) |
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In the world's population, more than half have... |
lactose intolerance |
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There are 2 different ways to absorb monosacs into the enterocyte |
1. SGLT-1 2. GLUT-5 |
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SGLT-1 is for... |
glucose, galactose and mannose intake |
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SGLT-1 works by... |
secondary active transport, symport -driven by Na+ gradient (est. by ATP hydrolysis and Na+/K+ pump) -works against sugar gradient |
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GLUT-5 is... |
-for fructose -Na+ independent -flows down concentration gradient |
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GLUT-2 is... |
-for all monosaccharides -located on contraluminal side of membrane -no energy needed, moves with concentration gradient |
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GLUT family of transporters are... |
-involved with facilitated diffusion -go with concentration gradient |
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GLUT-4 is... |
-insulin-dependent -inside cell -moves to surface upon insulin binding |
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the first pathway of catabolism is... |
glycolysis |
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nearlt universal metabolic pathway, occuring in every tissue... |
glycolysis |
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the amount of reactions in aerobic glycolysis... |
10 |
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the amount of reactions in anaerobic glycolysis... |
11 |
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aerobic glycolysis needs... |
-d-glucose, 2 PO34-, 2ADP, 2NAD+ |
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aerobic glycolysis produces... |
2 pyruvates, 2 H+, 2 ATP, 2 NADH + 2H2O |
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anaerobic glysolysis requires... |
d-glucose, 2 PO34-, 2ADP |
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anaerobic glycolysis produces... |
LACTATE, 2H+, 2 ATP+ 2 H2O |
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anaerobic glycolysis is more this than aerobic glycolysis |
favorable, greater negative delta g |
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the functions of glycolysis are... |
1. storage (glycogen) 2. Pentose PO34- Pathway > NADPH, 4-C, + 5C, + 7C, sugars 3. 2,3-BPG 4. special carb sx (gluconorate, glucosamine-6-P) 5. can utilize glycerol from triacylglycerol |
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the two stages of glycolysis are... |
1. the investment phase 2. the payoff phase |
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in the investment phase.. |
-glucose is phosphorylated, but needs 2 ATPs -glyceraldehyde 3-P is produced |
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in the payoff stage... |
G3P is converted to either: -pyruvate -lactate through redox steps |
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the product of step 1 glycolysis is... |
G6P |
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G6P is.. |
-negatively charged -trapped inside cell -can't be used as transporter (i.e. glut4) |
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Trapping of sugar is from... |
phosphorylation (negative charge) |
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Important things about Step 1 Glycolysis.... |
1. IRREVERSIBLE 2. uses hexokinase (*except LIVER = GLUCOKINASE) 3. step is not yet committed |
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Glucokinase has... |
higher Km for glucose than hexokinase |
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at normal blood glucose concentrations, hexokinase is... |
fully saturated |
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at normal blood glucose concentrations, glucokinase is... |
not saturated |
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Step 2 of glycolysis... |
-G6P isomerized to F6P -enzyme: glucose PO34- isomerase -readily reversible |
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Step 3 Glycolysis... |
-uses ATP -F6P > F1,6P -enzyme: PFK1 -2nd of 2 priming rxns |
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PFK1 is inhibited by... |
-ATP -low pH -CITRATE |
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PFK1 is activated by... |
-AMP -F-2,6 bi-PO34- |
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Step 4 Glycolysis... |
-F-1,6 bi-PO34 CLEAVED -2 products DHAP +G3P (G3P > glycolysis) -enzyme: aldolase -reversible |
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Step 5 Glycolysis... |
-isomerization > G3P -enzyme: triose phosphate isomerase -needs 2 ATP |
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Steps 6-10/11 Glycolysis... |
-produce 2x/glucose |
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Step 6 Glycolysis... |
-G3P oxidized > 1,3-bisphosphoglycerate *reduces NAD+ > NADH |
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NADH produced from Step 6 Glycolysis can either... |
-used for lactate conversion -pass electrons into mitochondria > ATP |
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Step 7 Glycolysis |
*First ATP generating step aka substrate level phosphorylation |
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Step 8 Glycolysis |
-OPO32- shifted from C-3 > C-2 -enzyme: phosphoglycerate mutase |
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What is a mutase? |
enzyme transfers functional group from one position to another on same molecule |
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Step 9 Glycolysis |
-dehydration rxn -product = phosphoenolpyrivate (PEP) enzyme: enolase |
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Step 10 Glycolysis |
*2nd of substrate level phosphorylation rxns -irreversible *important regulatory step in liver -enzyme: pyruvate kinase |
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in glycolysis, the conversion of glucose > pyruvate produces... |
-net 2 ATP |
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the 3 irreversible rxns of Glycolysis are... |
-hexokinase -PFK-1 -pyruvate kinase |
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Step 11 Glycolysis... |
-occurs only in anaerobic conditions (intense activity, or mitochondria-poor tissues) -enzyme: lactate DH -needs NADH -regenerates NAD+ = important for continued glycolysis |
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Initial glucose uptake has what affect on glycolysis. |
Another regulatory mechanism used to cells |
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4 mechanisms control glycolysis or its enzymes... |
-hormonal regulation -allosteric regulation -covalent modification -sequestration |
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the sx of kinases in glycolysis is... |
-stimulated by inslin -inhibited by glucagon |
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hormone stimulation of glycolysis kinases results in... |
-20-40x activity |
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regular consumption of carbs/well-fed state results in... |
facoring glycolysis liver > store energy as fatty acids |
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Hexokinase... |
-has low Km for glucose compared to glucose concentrations -saturated (vmax) at blood glucose concentrations -STRONGLY inhibited by G6P (so G6P doesn't hog PO34-) |
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Glucokinase... |
-turned off ONLY at high glucose concentrations -in beta cells, it's how b senses glucose and secretes insulin -not inhibited by G6P -indirectly inhibited F6P -inhibited by GKRP |
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GKRP is respinsible for... |
-sequestering glucominase inside nucleus |
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F6P promotes the binding of... |
glucokinase and GKRP -overcome in large glucose concentration as glucose triggets dissociation |
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F1P activity... |
-activates glucokinase -promotes dissociation of glucokinase and GKRP |
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effect of F1P... |
adverse effect aka hypertriacylglycetolemia from excess dietary fructose consumption |
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glucokinase sx induced by... |
insulin (few hours) |
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glucokinase gene expression indirectly... |
influence by glucose, since glucose stimulates insulin production |
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diabetic PT causes... |
glucokinase deficiency (no insulin) despite high glucose > liver not good buffer |
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PFK1 special role in Glycolysis |
*MAJOR regulator! -influenced and promoted by insulin -dependent on F2,6-BP (and therefore PFK2) |
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PFK2 is important since it... |
phosphorylates F6P > F2,6P -bifunctional enzyme has PFK2 activity + BPase activity (F1,6BP) |
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In well-fed state PFK2/FBP2... |
not phosphorylated > PFK2 active > promotes glycolysis/inhibits gluconeogenesis |
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In starved state, PFK2/FBP2... |
glucagon phosphorylates > activates F26BP > dephosphorylates F2,6BP >stops glycolysis |
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two forms of Pyruvate Kinase... |
- L-form = liver > extensively regulated -M-form = muscle and brain > not regulated |
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L-form Pyruvate Kinase is inhibited by... |
-ATP -Alanine -glucagon -phosphorylation > cAMP > PKA |
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the presence of Alanine promotes... |
-gluconeogenesis (starting material of process) |
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L-form PK is activated by... |
F1,6BP *linked and regulated by PFK1 -dephosphorylation -insulin |
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PK deficiency |
-rare but -most common genetic defect of glycolytic pathway -causes hemolytic anemia |
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PK hemolytic anemia happens bc... |
-deficiency of PK > less ATP sx > ion pumps (esp Na+/K+ pump) > swell > lyse = excessive erythrocyte destruction |
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NADH does not regenerate in this process... |
aerobic glycolysis |
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Anaerobic glycolysis regenerates... |
NAD+ from oxidation of NADH |
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oxidized NAD+ remains... |
-in cytoplasm, even though electrons are oassed to mitochondria for ETC |
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two shuttle systems transport reducing agents from cytosol > mitochondria are... |
1. G3P shuttle 2. malate-aspartate shuttle |
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Malate-aspartate shuttle is used mostly by... |
the liver |
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G3P shuttle is used more extensively in... |
muscle cells |
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the 2 shuttle systems are... |
-irreversible -unidirectional (ONLY from cytosol > mitosol NOT from mitosol > cytosol) |
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G3P regenerates... |
NAD+ by transferring electrons from NADH > DHAP > G3P > gives electrons to G3P DH (inner mito membrane facing cytoplasm) > FAD+ as cofactor, aceepts electrons |
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G3P shuttle produces... |
1 less ATP since gives electrons > FADH2 |
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G3P from G3P shuttle does not... |
penetrate inner mito. membrane |
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Malate shuttle products... |
-regeneration of NAD+ from NADH (cytosol) -NAD+ > NADH (mitosol) |
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OAA is important in maintaining NAD+/NADH balance... |
accepts electrons from NADH > malate > leaves cytosol > enters mitochondria > gives electrons to mito NAD+ > sx NADH becomes OAA |
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OAA can reenter cytosol by... |
receiving Glu group > transanimated > Asp |
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as mitochondrial OAA is transanimated, Glu... |
becomes alpha keto-glutarate and crosses into cytosol with Asp so that aKG can accept Glu in cytosol and Asp > OAA > available to be reduced again |
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2,3BPG is sx... |
-by enzyme" 2,3-BPG mutase/phosphatase |
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2,3BPG mutase/phosphatase converts... |
-1,3-BPG > 2,3-BPG -2,3-BPG > 3-PG |
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BPG shunt in RBC... |
makes NO NET ATP bc bypass phosphoglycerate kinase step! |
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Normal blood glucose level is... |
10 g < 1/5 teaspoon sugar! |
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hypoglycenic coma glucose levels... |
40 mg/dL |
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diabetes mellitus levels... |
125 mg/dL |
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cells that use glucose as primary fuel |
-brain -RBC -kidney medulla -lens -cornea -testis |
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brain consumes... |
200 g glucose/day |
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at concentration of only 10 mg/dL blood glucose is... |
constantly replenished |
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we are in glucose homeostasis when... |
our diet, glycolysis and gluconeogenesis are in balance |
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gluconeogenesis is... |
making glucose from non-carb carbon sources |
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gluconeogenesis happens during... |
fasting, starvation, low-carb diet or intense exercise |
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Most gluconeogenesis occurs... |
in the liver |
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In a prolonged starved state, up to 40% of glycolysis can occur... |
in the kidney |
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Gluconeogenesis borrows Glycolysis steps... |
2, 4, 5, 6, 7, 8, 9 |
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Gluconeogenesis does not have glycolysis steps... |
1, 3, 10 (rate limiting, highly controlled steps) |
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The new rxns of Gluconeogenesis provide... |
-new favorable rxns (spontaneous) -new regulation |
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Gluconeogenesis NEW Step 1... |
Pyruvate > PEP via 2 coupling rxns 1. pyruvate > OAA needs ATP! enzyme: pyruvate carboxylase 2. OAA > PEP enzyme: PEP carboxykinase (PEPCK) needs GTP! |
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Pyruvate Carboxylase is dependent on... |
Biotin (Vit B7) |
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Pyruvate Carboxylase produces... |
joins bicarbonate + pyruvate > OAA in mito (producing NADH) > malate > cross into cytoplasm |
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PEPCK simultaneously... |
-decarboxylates and phosphorylates OAA > PEP -requires GTP |
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Gluconeogenesis requires this to make 1 glucose... |
-4 ATPs (2 steps use ATP/pyruvate×2/glucose) |
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PEP to F1,6BP in Gluneogenesis are... |
same as Glycolysis, in reverse |
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In gluconeogenesis F1,6BP is... |
-dephosphorylated > F6P -enzyme: F1,6BPase |
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In gluconeogenesis F6P is converted to... |
-G6P -enzyme: phosphoglucose isomerase |
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In gluconeogenesis G6P is... |
-converted to glucose -enzyme: G6Pase (not hexokinase) |
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In gluconeogenesis, in order to reach its enzyme G6P... |
has to be transported from cyto > inside ER > G6Pase -uses translocase |
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After Gluconeogenesis, GLUT 7 |
transports glucose from ER > cytosol |
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After Gluconeogenesis, GLUT 2 is... |
used to get new glucose from cytosol to bloodstream |
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Inputs of Gluconeogenesis... |
2 NADH + 4 ATP + 2 GTP + 2 pyruvate |
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Products of Gluconeogenesis... |
glucose + 4 ADP + 2 GDP + 6 Pi + 2NAD+ + 2H+ |
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Unique regulation of Gluconeogenesis... |
*PFK-1 |
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In Gluconeogenesis, PFK1 is inhibited by... |
-F2,6BP and AMP thus promoting Glycolysis |
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In Gluconeogenesis, F1,6BPase is stimulated by... |
CITRATE, which also inhibits PFK1 (decreasing glycolysis) |
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Ace CoA is... |
-an allosteric effector of pyruvate carboxylase > promotes gluconeogenesis -inhibits PDH |
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F6P is... |
-an intermediate of gluconeogenesis -activates glucokinase inhibitor protein > inactivates glucokinase > x step 1 Glycolysis |
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Glucagon has this effect in adipose tissue... |
activates lipases > frees up fatty acids bloodstream |
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In Gluconeogenesis Glucagon/Epi... |
-increase G6Pase; F1,6-BPase; PEP-caroxykinase activity |
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In gluconeogenesis insulin... |
decreases PEP carboxykinase activity |
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Carbon sources for Gluconeogenesis... |
lactate, pyruvate, amino acids, glycerol, proprionate, other sugars |
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muscle protein is a major precursor to... |
blood glucose |
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we lose both muscle and adipose tissue in.. |
prolonged fasting, malnutrition or starvation states |
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lactacte comes primarily from... |
RBCs and muscle |
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lactate serves as... |
predominant source of carbon for gluconeogenesis |
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In the Cori Cyle |
lactate leaves cell (produced during anaerobic lactate DH rxn) > bloodstream > liver > converted to glucose > returns to blood > travels to target tissue |
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lactate DH converts... |
-pyruvate > lactate oxidizing NADH > NAD+ -lactate > pyruvate reducing NAD+ > NADH |
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Alanine Transaminase converts... |
Glu + Pyruvate > a-KG + Ala |
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Glucose/Alanine Cycle... |
-muscles > AAs > Nitrogen > pyruvate > 2 Ala -enzyme: alanime transaminase -alanine > liver > pyruvate for gluconeogenesis or TCA -nitrogen portion enters urea cycle -pyruvate > glucose -AA nitrogen > urea > excreted by kidney |
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LEUCINE and LYSINE cannot be... |
degraded to pyruvate or participate in TCA |
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When glycogen stores are depleted during exertion (muscle) or fasting (liver)... |
muscles are catabolized > AAs > blood glucose |
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Catabolizing triacylgerol produces... |
Glycerol + Ace CoA |
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net gain of glucose cannot use carbons sourced from... |
fatty acids |
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fatty acids broken down from beta oxidation... |
-produce ace CoA > enter TCA cycle -expelled as 2 CO2 = no net gain of carbon |
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Glycerol Kinase is located... |
-only in the liver -can convert glycerol > G3P > DHAP > gluconeogenesis -enzyme: G3P DH -FAD+ > FADH2 |
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Propionyl-CoA is... |
a terminal oxidation product from the beta-oxidation of odd # carbon atoms of fatty acids |
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Propionyl-CoA is converted to... |
succinyl CoA (TCA intermediate) > can feed gluconeogenesis |
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Elevated Alcohol can lead to... |
gluconeogenesis is favored: 1. high levels of NADH cytoplasm > shuttled to mitochondria > OAA into malate (ethanol + NAD+ > acetylaldehyde + NADH + H+) 2. lactate production is favored, pyruvate limited . DHAP > G3P 3. DHAP > G3P(conditions favor glycolysis) (conditions favor glycolysis) |
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Fructose and galactose are one of few... |
monosaccs significantly present in metabolism |
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Galactose is important part of... |
cell's structural carbohydrates |
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Once inside the cell, most sugars are... |
phosphorylated, can't pass membrane > trapped |
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major source of fructose is... |
sucrose |
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when sucrose is cleaved, results in equal... |
parts fructose and galactose |
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fructose... |
1. depends on insulin for entry into cell 2. does not promote insulin secretion (unlike glucose) |
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to enter intermediate metabolic pathways, fructose must... |
be phosphorylated |
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fructose is phosphorylated by... |
hexokinase or fructokinase (more often) |
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hexokinase phosphorylates fructose... |
only when fructose levels are very high (since it has a high km for glucose) |
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Drawback of Gluconeogenesis... |
consistent but SLOW |
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Drawback of Gluconeogenesis... |
consistent but SLOW |
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GLYCOGEN is preferred storage over glucose bc... |
rapidly mobilizable! |
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In the absence of dietary glucose... |
glycogen is released from liver, especially muscle glycogen during exercise |
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The primary structure of Glycogen is... |
alpha-1,4 linkage every 8-10 glucosyl residues -alpha-1,4 linkages × 100,000/glycogen molecule |
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branching of glycogen allows... |
more sotes for degradation and sx so metabolism happens quicker |
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More glycogen is found in these tissues... |
muscle and liver |
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Glycogen stores increase in... |
well-fed state |
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Liver stores of glycogen help... |
maintain blood glucose levels |
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Muscles stores of glycogen are not... |
used to maintain blood glucose levels |
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Each glucosyl residue addition on glycogen requires... |
2 ATPs |
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Glycogenolysis and Glycolysis to lactate yield... |
3 ATPs |
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Glycogen sx and Glycogenolysis degradation to lactate yield... |
1 ATP |
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Why glucose cannot be stored... |
osmotically active and ATP pump would be needed against its gradient |
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The advantage of Glycogen transport over Glucose... |
glycogen does not change osmolarity like glucose |
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The first step of Glycogenesis is... |
the same as Step 1 Glycolysis |
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Step 2 Glycogenesis... |
G6P > G1P enzyme: phosphoglucomutase |
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alpha-D-glucise attached to UDP is... |
source of growing glycogen molecule |
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Step 3 Glycogenesis... |
G1P + UTP > UDP-glucose enzyme: UDP-glucode pyrophosphorylase *uses 2 UMPs energy to elongate chain |
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Glycogen synthase is responsible for... |
making alpha-1,4 linkages in glycogen |
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Glycogen synthase cannot... |
-use free glucose -can only elongate on existing chains -needs a primer |
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3 kinds of glycogen primers... |
1. fragment of glycogen 2. glycogenin 3. specific tyrosine residue |
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glycogen fragment can be a primer in... |
cells that still have glycogen stores (not depleted) |
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Glycogenin... |
-is a glycogen primer for de-novo sx -accepts glucose residues from UDP-g |
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A specific tyrosine side chain... |
is the site where initial glycosydl residue is added |
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Glycogenin can catalyze... |
the transfer of first few glucose molecules from UDP-glucose in glycogenesis |
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the transfer of glucose from UDP-glucose needs... |
non-reducing end, not bound by glycogenin > new bond formed btw hydroxyl on C-1 of activated and C-4 of accepting glucosyl residue |
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Fructokinase is located in... |
-liver, kidney, small intestine -needs ATP -produces F1P |
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F1P cannot be converted to... |
F1,6-P |
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F1P produces... |
DHAP and glyceraldehyde enzyme: aldolase B |
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DHAP can directly enter... |
glycolysis and gluconeogenesis |
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Aldose reductase produces... |
reduces glucose > sorbitol |
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Aldose reductase is in specific tissues such as... |
retina, peripheral nerves, kidney |
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Sorbitol DH... |
-oxidizes sorbitol > fructose -in certain cells: liver, ovaries, sperm, seminal vesicles |
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In fructosuria... |
deficiency of fructokinase > high blood fructose > eventually 90% metabolized |
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Hereditary Fructose Intolerance (HFI) is... |
-autosomal recessive disorder -deficiency of aldolase B > buildup F1P > traps Pi > inhibits glycogen breakdown + gluconeogenesis |
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symptoms of HFI... |
abdominal pain, vomiting, hypoglycemia, hepatic/renal failure and death in infants, distaste for sweet foods |
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alpha-1,6 bond in glycogen is formed when... |
amylo-alpha-1,4 -> alpha-1,6-transglucosidase teansfer glycosyl residues from non-reducing end of glycogen (breaking 1,4-chain) to another residue > forming 1,6-chain |
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Degradation of Glycogen begins with.. |
-alpha-1,4 bonds broken > G1P -alpha-1,6 bonds brokrn > free glucose |
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Glycogen phosphorylase... |
cleaves alpha-1,4 bonds > 4 glucosyl units > releases G1P |
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Limit dextrin is... |
structure at branch point in glycogen, cannot be degraded further, branches are removed |
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Oligo-alpha(1,4) -> alpha(1,4)-glucan transferase... |
removes outer three residues attached at branch point > transfer to non-reducing end for more processing, leaving just limit dextrin |
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amylo-alpha(1,6)-glucosidase... |
transfer the 1,6 branch of glycogen > free glucose |
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oligo alpha-1,4 transferase and amylo-alpha-1,6 glucosidase... |
are debranching enzymes |
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Phosphoglucomutase converts... |
G1P > G6P |
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G6P Translocase moves... |
G6P into ER |
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G6P phosphatase converts... |
G6P > glucose in the ER |
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Muscles lacks this enzyme of Glycogenolysis... |
G6P phosphatase > cannot make free glucose (comes from 1,6 branches) |
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lysosomal enzyme alpha-1,4-glucosidase(acid malase) purpose... |
is unknown but deficiency > Pompe disease |
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Glycogen metabolism controlls regulating enzymes... |
-glycogen synthase -glycogen phosphorylase through allosteric or hormonal means |
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Glycogen synthase is allosterically activated by... |
HIGH G6P levels in liver, occuring in well-fed state |
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Glycogen Phosphorylase is allosterically inihibted by... |
G6P, ATP and glucose |
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the muscle form of Glycogen Phosphorylase is stimulated by... |
HIGH levels of calcium |
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the enzyme family of glycogen phosphorylases can be... |
regulated differently bc they are isozymes |
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the binding of what hormones signal the need for glycogen catabolism... |
glucagon and epinephrine |
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membrane receptor for glucagon/epinephrine is... |
gcpr > activates adenylyl cyclase > cAMP > regulatory units pKA > active pKA > phosphorylates inactive glycogen phosphorylase kinase B > actiavted glycogen phosphorylase kinase A |
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Glycogen phosphorylase kinase exista in... |
2 forms: -dephosphorylated/inactive B form -phosphorylated/active A form |
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active phosphorylase kinase... |
phosphorylates glycogen phosphorylase > degrades glycogen |
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in extreme conditions of anorexia or ATP depletion... |
AMP can activate glycogen phosphorylase independent of phosphorylation |
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Protein Phosphatase 1 (PP1) is stimulated through... |
an insulin dependent pathway |
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In PP1 pathway... |
insilin binds to surface receptor > PP1 dephosphorylates both glycogen phosphorylase and glycogen phosphorylase kinase > inhibits glycogen catabolism |
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muscle contraction may require... |
urgent need for ATP > muscle's glycogen storage provides supply |
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the activated calmodulin complex is... |
a sibunit of many protein complexes including glycogen phosphorylase kinase |
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glycogen synthase is regulated opposite... |
of glycogen phosphorylase |
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the active form of glycogen synthase is. . |
active in the non-phosphorylated form |
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the phosphorylation of glycogen synthase by pKA... |
-inactivates it -can happen at multiple levels -level of phosphorylation = level of inactivation |
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the binding of glucagon/epinephrine to surface receptors inactivates... |
glycogen synthase through pKA phosphorylation |
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binding of insulin to receptors stimulates... |
PP1 activity > dephosphorylates inactive glycogen synthase abd glycogeb sx be continued |
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Pentose Phosphate Pathway is... |
-anabolic -generates NADPH -provides ribose-5-phosphate (R5P) -interconvert C3, C4, C7 > further use or recycle through glycolysis |
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the two phases of pentose phosphate pathway are... |
1. 2 oxidative irreversible rxns 2. non-oxidative rxns |
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In the 1st phase of pentose phosphate pathway... |
G6P is decarboxylated via 2 oxidative rxns > pentose sugar + 2 NADPH + CO2 |
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In the 2nd phase of Pentose Phosphate Pathway... |
pentose + ribulose-5-phosphate > other sugars + ribose-5-phosphate via non-oxidative rxns |
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ribose-5-phosphate is used for... |
nucleotide sx (and glycolytic intermediates?) |
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Step 1 Pentose Phosphate Pathway... |
*most highly regulated step -G6P > 6 phodphogluconolactone > relases NADPH -enzyme: G6PDH |
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NADPH is... |
-a potent negative regulator of G6PDH -high energy molecule that is involved with fatty acid sx -similar to NADH, however electrons not transferred to oxygen but rather the molecule being sx |
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when NADPH levels are high... |
pentose phosphate pathway is inhibited |
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Step 2 and Step 3 of Phase 1 i Pentose Phosphate Pathway... |
produce: NADPH + CO2 + R5P |
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the reversible rxns of pentose phosphate pathway allow... |
Ribulose-5P converted into: -ribose-5P > nucleotide sx -or glycolytic interm. = G3P or F6P |
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from the nom-oxidative rxns of pentose phosphate pathway, interconversion of... |
3-7 carbon sugars need a variety of enzymes like epimerases, isomerases, transaldolases and transketolases |
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Uses of NADPH include... |
-reductive biosx -removal of reactive oxygen species -defense against bacterial infections -sx of nitric oxide |
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NADPH rxn equation... |
8 ace CoA + 7 ATP + 14 (NADPH + H+) = palmitate + 8 coA + 7 ADP + 14 NADP + 6 H2O |
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the 3 enzymes which protect cell from oxidative stress are... |
1. superoxide mutases 2. catalase 3. glutathione peroxidases |
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Superoxide Mutases are... |
enzymes that catalyze the conversion of two superoxides into hydrogen peroxide and oxygen |
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Superoxide dismutases are helpful bc... |
-hydrogen peroxide less toxic than superoxide -accelerates detox rxn by 10,000x |
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Catalase is... |
-found in peroxisomes -degrades hydrogen peroxide > H2O + O2 (product of SOD rxn) |
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Glutathione Peroxidases... |
-degrade H2O2 -reduce organic peroxides > alcohols (route to eliminate toxins) -contain selenium |
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G6PDH deficiency... |
-is x-linked recessive disorder -features hemolytic anemia -most common disease-producing enzyme abnormality > 400+ million -200,000 new cases/yr in US -highest prevalence in Middle East, Africa, Asia, Med -lifespan is somewhat shortened -female carriers have increased resistance to malaria |
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why does G6PDH deficiency cause hemolytic anemia? |
cells lacking G6PDH > produce less NADPH > can't reduce glutathione (GSH) |
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Glutathione... |
-agent which fights reactive oxygen species -plays role in repairing oxidative damage to cell membrane -made of gammaGlu-Cys-Gly |
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Glutathione reductase... |
-NADPH-dependent -reduces glutathione > reduced form |
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In oxidized form, Glutathione... |
forms S-S bridge with another GSH |
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Without properties of glutathione... |
decrease in cellular detoxification of free radicals and peroxides > accumulation of denatured proteins = Heinz bodies |
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G6PDH deficiency is most severe... |
im RBC as pentose phosphate pathway is only way to generate NADPH |
