When does de novo synethesis of glucose occur?
This is gluconogenosis and this occurs during fasting when blood glucose levels are falling and glucose is needed for certain organs
What and when does glycogenesis take place?
When glucose levels from diet are more than needed, the excess is stored as glycogen through glycogenesis
When need the glycogen is degraded through glycogenolysis
Go from Glycogen to lactate
What are the two minor pathways of glucose
Hexose monophosphate shunt- produces ribose-phosphate for nucleotide synthesis and NADPH that supplies power for bopsynthetic reactoin (making fatty acids)
Galatose and fructose metabolime-- can sytnehsize sugar and sugar derivitatives.
Where can glucose be obtained from
Storage (glycogen) or diet
In storage glycogen is cnoverted to glucose or glucose 6-phosphate
Glcuose from diet has different sources. What are they? examples of each kind
Monosaccarides- honey and fruit- these can be easily absorbed by enterocytes
Disaccarides- milk sugar (lacatose) and table sugar (sucrose)- hudorlyzed by enzymes in the brush border of intestinal tract
Polysaccarides- starch (from plants) and glycogen(animals from their storage) and they contain alpha 1-4 glycosdies linkages and alpha 1-6 glycosidic linkages
What is lactose, sucrose and trehalose composed of
Lactose- glucose and galactose
Sucrose- glucose and fructose
Where does the major daily caloric intake come from? How is each absorbed?
CARBS! mono, di and poly
1. Monosaccharides are absorbed directly;
2. disaccharides are digested by
intestinal surface enzymes
3. polysaccharides need to
be reduced to smaller molecules
Explain the absorption of strach and glycogen
1. The amylose chains (1-4 glycosidic chain/ linear) are degraded by alpha-amylase in the saliva and pancreatic juices
making glucose, maltose (di) and maltotriose (tri).
2. The 1-6 glycosidic chains (amylopectin/branched) are hydolyzed by isomaltase
3. Further digestion of oligiosaccharides occurs on the surface of the intestinal epithelial cells by alpha-glucosidases (maltases)
4. Oligosacc not hydolyzed by amlyase or intesintal enzymes reach the ileum where bateriametablizes the sugas anerobically to short fatty acids, H2, methane and CO2
What happens in pathology of digestion? Explain oral tolerance test>
Undigested disaccharides go to the LI and they cause osmotic diarheea. Bacterial digestion results in production of large amounts of CO2, methane and hydrogen gas.
Oral tolerance test can measure the amout of hydrogen gas in a breath and can identify enzyme deficieny
What can cause disaccharide intolerance?
1. Loss of brush cells in intestinal tract
2. Intesitnal disease
3. Drugs that damage the mucosa of the SI
Temp disorder can lead to severe diarhea
Explain what happens when someone is lactase intolerant
Latase definicity so lactose passes into the LI where it is digested by bacteria causing GI distress, cramping, bloating due to the CO2 and methane that is being produced.
What is isomaltase sucrose deficienty
Results in intolerance to sucrose. in about 10% of greenland eskimos and 2% of NAmericans are heterozygous
Where do intestinal cells obtain energy?
From glutamine metabolism--- they don't depend on glucose
How and by what are monosacc absorbed?
What is the exception?
By entercytes through facilitated diffusion
Pentoses and L-sugars enter through passive transport (so we can use xylose to test ability of mucosal cells for absorption)
How does glucose and ____ get absorbed?
Difference from mannose
Through the Na-monosaccharide (SGLT-1) co transporter driven by Na gradient and the hydrolyze of ATP, so the mono sacc can go against it's gradient
** this is different from the Na-dependent transporter used for manose***
What does GLUT-5 transport?
What passes through GLUT-2?
Glut -2 transports all monosacc through the membrane of the lumen into the capillaries. CAn pas glucose, galactose, fructose
steps after monosacc have passed into the capillary through the Glut-2
Monosaccs. go to the liver. Gluocse is distributed into general circulation, while galactose, fructose and mannose are processed by the liver
Why can every cell use glycolysis? Names cells that only use it
Because its anerobic and doesn't require O2
Scelera, retina, RBC, cornea-- so they rely on the 2 ATPs formed by glycolysis
Name some functions of glycolysis
1. Yields 2 atps (cells that have no mitochondria rely solely on these two ATPs)
2. Sets the stage for aerobic oxidation because pyruvate can become Acytl CoA
3. Stores glycogen which is an intermediate for carb storage
4. Supplies intermediates for pentose phosphate pathway (making of NADPH and 4,5,7 Carbon sugars)
5. Supplies intermediates for 2-3 BPG
6. Supplies intermediates for special carbohydrate synthesis
7. can take up glycerol from triacykygylercols
Where does glycolysis, TCA and oxidative phosphorylation take place
Glycolysis – in cytosol
TCA – in mitochondrial matrix
Electron transport and oxidative phosphorylation – in inner membrane and inter-membrane
Glucose--> pyruvate 2 ATP
Pyruvate--> CO2 2 ATP
NADH+H (FADH2)-->H2O 34 ATP
1. Dependent on glucose that make pyruvate
2. Dependent on glucose that make lactate
3. Dependent on glycolysis b/c of low mitochondria
1. Dependent on glucose that make pyruvate-- brain
2. Dependent on glucose that make lactate-- No mitochondria so make pyruvate- RBC, retina, sclera, lens
3. Dependent on glycolysis b/c of low mitochondria-- renal medulla, testis, WBC, Whte mucle fibers
*** heart is aerobic but uses mostly fatty acids**
3 stages of glycolysis
Explain the first
3. oxidareduction phosphorylation
The priming stage is activating the pathway by converting glucose to fructose 1-6 biphosphate (this requires 2ATPs).
here takes place the 1st regulatory step. Hexokinase (and glucokinase an isoenzyme) both run phosphorylation of glcuose to glucose 6 phosphate where we have a junction point in metabolism
Right after hexokinase is PFK-1 (2nd regulatory step MOST important and rate limiting- invest 1 ATP in PFK-1)--- this decides to run or stop glycolysis
Glucose 6-phosphate is a junction point inmetabloim.. What can form from it?
1. can go into gylcolysis,
2. can go into glycogen for energy storage,
3. can go tinto glucuronate for carb synthesis,
4. can go into pentose phosphate pathway to synthesis NADPH and 4,5,7Chain Carbon Sugars)
What is the 2nd step of glycosis. Explain it
Spiltting- sptil our 6 carbon sugar into two 3-carbon sugars byt the enzyme aldolase one is glyceraldhyde 3-phosphate (the one that goes into glycolysis) and Dihydroxyacteon phophate. this step is reversible
For fructose the enzyme is Aldolase-B
What is the 3rd and final step of glycolysis. Explain it.
Oxidoreduction - phosphorylation stage prodcues 4 ATPs (2 net). 1. We start with the glyceraldyhyde 3 phosphate (from the spilting stage); here the enzyme GAPDH oxidzes(aerobic conditions) the aldyhyde group to carboxylic acid with reductio of NAD+ to NADH (making about 3 ATPs)
2. Next phospoglycerate kinase produces 2 ATPs per glucose from 1-3 BPG by substrate level phosphorylation because it occurs with substrate w/o invovlement of oxidative phosphorylation
3. THeo 3_ phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase
4. The 2-phosphglyercate to phosphenolpyruvate by enolse
5. Last step before aerobic is phosophenolpyruvate to pyruvate by pyruvatekinase. this is the 2nd substrate level phosphorylation, 3rd regulatory step and makes 2ATP/glcuose
GAPDH- is liek a housekeeping gene because it's in every cell andit is not regulated.
Explain the RBC shunt
1-3 BPG isn't forming 3-phosphglycerate and 2 ATPS through phosphglycerate kinase but instead we are making 2-3 BPG with mutase, So no net ATP and that RBC are taking up much more glycose that you would think is needed because they are shunting up to 25% of glucose for no energy profuction but 2-3 BPG production
End product under anerobic conditions
Can be utlized by liver, skeltal, and muscle cells and turning it back into pyruvate. Liver can use lactate for glucose production (gluconeogenisis)
Why do we need a balance of NAD+ and NADH
Just like anything we need a balacne. GAPDH uses NAD+ to make NADH so we need to have NAD+ avliable for the next cycle for GAPDH
Lactase dehydronease makes NADH reoxidize to NAD+ by produsing lactate
Aeorboic- NADH through the mitochondria becomes NAD
two routes of reoxidizing NADH back to NAD+
1. Lactase dehydronease makes NADH reoxidize to NAD+ by produsing lactate
2. Aeorboic- NADH through the mitochondria becomes NAD+ through the shuttling of H+
What are two shuttle systems? Why arethey important
1. Malate-asprate shuttle (mostly liver)... oxolacetate reduces to malate making NAD+ (in the cytosol) and then NADH is reproduced in the mitochondrial matrix
2. Glycerol phosphate shuttle(mostly muscle)-- NADH is oxidized back to NAD+ in the cytosol close to the mitochondria membrane where DHAP--> Glycerol 3-phosphate which makes FADH2 in the inner mitochondrial matrix
***Less favored to use glycerol phosphate because you start with NADH (3 ATP potential) and end with FADH2(2 ATP potential), so when we use malate-asparate we make 38ATP (10 NADH, 2FADH, 2 ATP, 2 GTP) when we use the glyverol phosphate 36ATP (8NADH, 4FADH, 2 GTP, 2ATP)
POisions that inhibit glycolysis
Mercury and arsenate inhibit GAPDH (the enzyme used in the oxioreductin-phosphorylation stage of glycolysis to change Glyceraldehyde to 1-3 BPG by oxidizing carboylic acid and reduces NAD+ to NADH)
Fluoride inhibts enolase
PAthway of alchohol metabolism; why is this bad for you
Ethanol-----Alchol DH---> acetaldehyde----- Aldehyde DH--> acetate + NADH
More NADH uses the same shuttle as glycolysis so when too much alchol you're in overload of the shuttle and you lose your balancce of NADH and NAD+ and glycolysis stops
Why shouldn't we mix drugs and alchols
Drugs are removed from the body through liver through two systems Glucononic acid and and cytochrome P-450 system. Alcohol inhibits the cytochrome P-450 system so drugs are circulating . Gluconoric acid system produces NADH as well (like ethanol/alcohol) so the shuttle stops and the glycolysis stops and removal stops.
3 regulatory enzymes in glycoslysis
D glucose--- Hexokinase--> Glucose 6-P
Fructose 6-P----PFK-1-> Fructose 1-6 Biphosphate
phosphenlpyruvate--- pyruvate kinase ---> pyruvate