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Catabolism
Breaking down energy containing nutrients to obtain high
energy intermediates (ATP, NADH, NADPH and FADH2+
TERM 2
Anabolism
DEFINITION 2
Using high energy sources to create cell macromolecules
from precursor molecules. These reactions are exergonic.
TERM 3
ATP
DEFINITION 3
Adenosine tri phosphate.Universal currency of the cell
because of high energy phosphate bonds within ATP.Allow for
connection between catabolism and anabolismBeta-Alpha
Bond > Beta-Gamma Bond >> Beta-Adenosine bond it terms
of energyProportion of adenine nucleotides as ATP ~ 70-90%
TERM 4
Cell Building Blocks
DEFINITION 4
Make up structures in the cell.Cost is expressed in high
usage of both ATP and NADPH
TERM 5
PCr
DEFINITION 5
Some cells use PCr as a source of energy (specifically
myocyte and neuron)
NADH, NADPH, FADH
Molecules are able to produce ATP through transfer of
protons in electrons in the electron transport chain
TERM 7
isulin Receptor
DEFINITION 7
Glucose sensor in pancreatic beta cells triggers secretion of
insulin:
TERM 8
Stereochemistry of Sugars
DEFINITION 8
Mammals use D optimal isomers in the metabolism of sugars.
A sugar is in D conformation if the reference carbon - the
chiral carbon closest to the carbonyl carbon - is the same a
D-glyceraldehdye (to right to fisher projection)
TERM 9
Aldoses
DEFINITION 9
A Monosaccharide that contains one aldehyde group per
molecule.
Changed to glucose via epimerase enzymes
Galactose cannot change to mannose via one reaction;
must use glucose as intermediate
TERM 10
Ketose
DEFINITION 10
A Monoshacarride where one carbonyl group is a ketone
EX --> Dihydroxyacetone
Glycoproteins
Branched chains (antennae) made up of complex sugars
where a sugar group of GlcNac is attached to an Asn residue
which makes it an N linked protein.The cell has enzymes to
create an elaborate antenna of the protein which is located
at key places on the protein
TERM 17
Proteoglycans
DEFINITION 17
Protein-carb structures with repeating disaccharide cores and
protein/sulfated sugar branches
TERM 18
Glucose Transporters in Human Genome
DEFINITION 18
Glucose is to big to undergo passive diffusionGLUT2: Brings
forth glucose into the liver, pancreas , and intestine at very
high concentrations. Allows removal of excess glucose from
bloodGLUT4: brings glucose into the muscle as lower
concentrations
TERM 19
Origins of Glycolysis
DEFINITION 19 Comes from dietary carbs- -> (starch and sucrose) digestion starts at mouth (alpha amylase breaks down glycosidic linkages) alpha amylase present in stomach and pancreas continues to break down molecule until glucose is free free glucose enters glycolysis Glycogen: Mobilized by phosphorolytic reaction catalyzed by glycogen phosphorylase to create G1P G1P is converted to G6P which can then enter glycolysis Fructose, Galactose, Mannose: They can undergo glycolysis after conversion to a phorphorylated derivate Fructokinase in liver catalyzes the phosphoyrlation of fructose to create G3P or F6P depending on site of phosphorylation Galactose is converted by epimerase to obtain G1- only after UDP is added Mannose undergoes phosphorylation to enter the cell as F6P TERM 20
Glycolysis (preparatory phase)
DEFINITION 20 Glucose is phorylated at C6 to form G6P. This is done by hexokinase and IT IS IRREVERSIBLE. ATP IS USED G6P is converted to F6P by phosphohexase isomerase G6P is phophorylated again to phosphofructokinase-1 in order to create Fructose 1,6 biphosphate. ATP IS USED F16BP is slipt to create glyceraldehyde-3-phosphate and DHAP (which is then converted back to glyceraldehyde 3 phosphate)
Payoff Phase
2 Glyceraldhyde 3 phosphate molecules are oxidized and
phosphorylated to form 1,3 biphosphoglycerate. 2
MOLECULES OF NADH IS GENERATED
In steps 7-10 energy is released by having phosphate being
removed by phosphoglycerate mutase and pyruvate kinase.
BOTH OF THESE STEPS ARE IRREVERSIBLE. The finalproduct
is pyruvate
TERM 22
Substrate level phosphorylation
DEFINITION 22
When the direct product of a reaction is ATP
TERM 23
Oxidative Phosphorylation
DEFINITION 23
Present when NADH or FADH2 is generated as these
molecules can later form ATP in the presence of oxygen in
the electron transport chain
TERM 24
Lactic Acid Fermentation
DEFINITION 24
Pyruvate is converted to lactate via lactate dehydrogenase in
order to obtain NAD+ which can stimulate glycolysis. This
allows for the production of ATP WITHOUT the use of oxygen.
Lactate eventually bring the body to a halt signalling that
oxygen is needed:
TERM 25
Alcohol Fermentation
DEFINITION 25
Occurs in yeastPryruvate is converted to acetaldehyde via
pyruvate decarboxylase and alcetaldyde is converted to
ethanol via alcohol dehydrogenase. Occurs under conditions
where there is no oxygen. When the yeast is 12% ethanol it
dies
Pyruvate conversion to PEP (Gluconeogenesis)
When lactate is the precursor: Pyruvate is transported from the cytosol into mito Pyruvate carboyxlase and coenzyme biotin converts the pyruvate to oxaloacetate in the mito oxaloacetate is converted to PEP via PEP carboxykinase which can then leave the mito When Alanine or Pyruvate is the precursor: oxaloacetate is converted to malate which can leave the membrane which is then converted back to oxaloacetate TWO NADH MOLECULES ARE OBTAINED TERM 32
Pyruvate Carboxylase
DEFINITION 32
Requires acetyl CoA as a positive effectorATP is a regulatory
element. High concentrations of ADP and AMP indicate a shut
down of the enzymeUses biotin to react
TERM 33
PEP Carboxykinase
DEFINITION 33
Inhibited by formation of PEP
TERM 34
Fructose 1,
Biphosphatase
DEFINITION 34 Levels of Fructose 2,6 biphophate will dictate to go through glycoslysis or gluconeogenesis.High F26BP = glycolysisLow F26BP = gluconeogenesisF26BP allosterically activates PFK-1 and deactivates Fructose 1,6 biphosphataseGlucagon lowers cellular level of F26BP therefore stimulating gluconeogenesis by activating FBPase-2 which breaks it downInsulin raises cellular level of F26BP therefore stimulating glycolysis TERM 35
Glucose-6-Phosphatase
DEFINITION 35
Only present in the liver
Allows for phosphate group to be clipped off G6P and for
glucose to be created
G6P stays in muscle to stimulate glycolysis
Liver transports G6P around the cell
Glycogen Stores
There are primarily in liver and muscleLiver:
glycogen stores are used to maintain blood glucose to
provide energy for other tissue
Muscle:
used solely by the tissue
TERM 37
Advantages of Glycogen Stores
DEFINITION 37
rich source of glucose for energy and carbon skeletons
4 Kcal/g (less than half of the energy of fat as it is
partially oxidized)
rapidly mobilized because of multi branches structure
TERM 38
Disadvantages of Stores
DEFINITION 38
only 30% of wet weight is carbohydrate
heavily relative to triglycerides as triglycerdies are
anhydrous (dry weight = wet weight)
limited in size
TERM 39
Glycogenoglysis
DEFINITION 39 Cleavage of glycogen stores to yield glucose residues for energy or to use for building blocks in anabolic processes: Glycogen Phosphorylase : hydrolyses glycosidic bonds using Pi in order to remove G1P from the chain Debranching Enzyme: Glycogen Phosphorylase acts repetitively on non reducing end of glycogen branches until it is 4 glucose residues away from the branch point. Transferase transfers 3 glucose residues to another end of the molecule and cleaves the free glucose remaining Phosphoglucometase: Changes G1P to G6P such that it can enter glycolysis TERM 40
Regulation of Glycogenoglysis
DEFINITION 40 Glucagon/epinephrine stimulates an increase in cAMP which activates PKA that phosphylates phosphrylase kinase which can then activate glycogen phosprylase. This cascade of reactions converts the inactive form (glycogen phosphorylase b) to the active form (glycogen phosphorylase a) This allows for intense amplification.PP1 can convert form a to from b. Insulin activates this enzyme
Steps of Citric Acid Cycle Yielding Energy
Step 3: Isocitrate is converted to alpha ketogluterate through isocitrate dehydrogenase. This releases NADH Step 5: Succinyl CoA is converted to Succinate by succinyl CoA synthetase. This releases GTP and CoA-SH Step 4: Alpha Ketogluterate is converted to Succinyl Coa by alpha ketogluterate dehydrogenase. This releases CO2 and CoA-SH Step 6: Succinate is converted fumerate via succinate dehydrogenase where is a double bond is introduced. FADH2 is released Step 7: Malate is converted to oxaloacetate though malate dehydrogenase. OH is oxidized and NADH is released TERM 47
Regulation of Citric Acid Cycle
DEFINITION 47
Calcium signals contraction and stimulates energy yielding
metabolism to replace the ATP consumed by contraction.
When ATP is high it will regulate the high energy yielding
cycle.
TERM 48
Loss of Intermediates and Replenishment
Steps (Citric Acid Cycle)
DEFINITION 48
When intermediates are removed for the cycle they are
replaced by anapldrotic reactions.Most important:In liver and
kidney where pyruvate is converted to oxaloacetate to help
regulate the cycle. It is catalyzed by pyruvate carboxylase
and it is an allotter regulator which needs acetyl CoA in order
to function
TERM 49
The Glyoxalate Cycle (Introduction)
DEFINITION 49 acetyl CoA condenses with oxaloacetate to form citrate Citrate is converted to isocitrate Isocitrate is cleaved by isocitrate lyase thereby forming succinate and glyoxylate (different that in CAC) Glyxoxylase then condenses with a second molecule of acetyl-CoA to yield alate which is catalyzed by malate synths Malate is then converted to oxalacetate with NADH This occurs in glyoxysomes that converts stored lipid into glucose. Very close to mito. Succinate leaves the cycle and enters CAC in mito such that Malate can be released and converted to glucose. TERM 50
Regulation of Glyoxalate Cycle through
isocitrate dehydrogenase
DEFINITION 50 Phosphorylation of isocitrate dehydrogenase in citric acid cycle by protein kinases then it is inactivated an all isocitrate is channelled into glyoxalate pathway When AMP and ADP are high there is reduced ATP which allows isoctirate dehydrogeanse to be activated. No glyoxyalate cycle occurs When AMP and ADP are low, ATP is high and CAC is not required so isocitrate dehydrogenase is inactivated and glyoxalate cycle occurs
The Pentose Phosphate Pathway (Oxidative
phase)
The pathway exists to generate NADPH (used by angels that synthesize fatty acids or steroids) and Ribose-5-P (building block)Creates GSH which is reduced glutathione. GSH protects the cell from highly reactive oxygen derivates by destroying hydrogen peroxide and hydroxyl free radicals. Regeneration of GSSH is through NADPHG6P dehydrogenase used Mg2+ as a cofactor TERM 52
Pentose Phosphate Pathway (Non Oxidative
Phase)
DEFINITION 52
Six 5C sugars are converted to 5 6C sugars using the
enzymes transketolase and transaldolase
Energy is supplied by thiamine pyrophaste TPPwhich
specializes in 2 carbon transfer
RIbose-5-phosphate is ultimately converted back to
Glucose-6-phosphate to continue the oxidative phase
TERM 53
Regulation of Pentose Phosphate Pathway
DEFINITION 53
When NADPH is in excess, NADPH inhibits G6P
dehydrogenase thereby shutting down the oxidative phase
TERM 54
Definition of Vitamins
DEFINITION 54
Substance that is not synthesized by the body BUT must
be provided in diet (sometimes but gut flora or sunshine -
vitD-)
essential for special function
first recognized with thiamine
required it small amounts per day but there is a
1000000x different between the amount required per
vitamin
TERM 55
Function of Vitamins
DEFINITION 55 Coenzymatic Fucntion (All B, C, and K vitamins) Antioxidant Function (vitamin c and K) --> mops up free radicals and peroxide Transcriptional Regulation (Vit A and D) --> fat soluble vitamins serve as specific ligands for certain genes. Vit D regulates calcium binding in intestine and kidney Vitamins do a bunch of general function as they can hold things like hydrogen,hydride,carbons,and CO2 that acts as a temporary transition state
Biotinidase
Biotinidase allows us to take in biotin and recycle it. If one
lack biotinidase we lose biotin every time we perform the
cycle. Avidin inhibits biotin and it is very hard to remove
form body
TERM 62
Human Biotin Deficiency
DEFINITION 62
If we lack biotin we have a buildup of precursors in biotin
reacting enzymes.To treat this we add a MEGABOSE of biotin.
Symptoms are reduced within 48 hoursThe case concluded
that human biotin deficiency was caused by a loss of
function in biotinidase which caused defective biotin
recycling enzyme
TERM 63
Lipids
Definition
DEFINITION 63 Biochemists definition of fat:Fatty acids (Prostaglandins): Metabolic field, Building blocks for other lipids, Intracellular ModulatorsGlyceral esters (Acyclglycerols and Phosphoglycerides): fatty acid storage, metabolic intermediates, membrane structureSphingolipids (Sphingomyelin and Glycosphingnolipids): membrane structure, membranes, and surface antigens TERM 64 DEFINITION 64
In sphingolipids the backbone is not glycerol
Phosopholipids have a hydrophilic group at the 3rd
position and fatty acid in the second position which
makes in amphipatic and ideal for membrane structure
TERM 65
Triacylglycerols
DEFINITION 65 When saturated (no double bonds) the structure can be found in solid form and back together. This is why these fats are an amazing source of storing energyWhen unsaturated (double bonds) they are liquid at room temperature and cannot back togetherNOTE: Butter is special as it has a high abundance of short saturated fatty acidsTo increase fluidity we can increase number of unsaturated fatty acids or shorten the fatty acid chain lengthGlycerol and three fatty acids
Glycerolphospholipid
Position one has a saturated fatty acidPosition two has an
unsaturated fatty acidOnly the X group varies and it is
usually polarThe charge and phosphate can often be
cancelled out by a positive charge on x group
(phosphatidylcholine)Molecules that are extremely charged
are often used in cell signalling
TERM 67
Sphingolipids
DEFINITION 67
These have similar structures to phospholipidsThey all have
same basic structure; however, the X group will usually
vary.The molecule is very rich in brain tissue and myelin
sheath for the option nerveThey are in large amounts in the
retina because they are great insulators (basic function)
TERM 68
A Fatty Acid
DEFINITION 68
Alpha carbon is next to carboxyl.Chemistry systematic
numbers:
count from carboxyl carbon (C1)
Nutritionist Functional Class Numbering
count from methyl carbon (N or omega)
Biochemists Enzymatic Greek Symptoms:
label carbons from C2 using greek alphabet
TERM 69
Why did Nature select Triglycerides as the
major long term storage for energy?
DEFINITION 69 Inert --> fatty acid would be reactive in free form but ester bond ties up COOH group in triglyceride Reduced --> triglyceride is almost all hydrocarbon (little oxygen and concentrated) Anyhydrous --> hydrophobic chains excluded water and it is light to carry around in fat depots DISADVANTAGE: Mobilization is slow --> in a deposit the large circle inside of it is a giant fat globule which lies the reason why it is so slow to metabolize TERM 70
Olestra
DEFINITION 70 8 fatty acids arranged around a single sucrose molecule: Artificial fat substitute Ester of sucrose instead of glycerol Cannot hydrolyze as lipase's in the gut cannot break it down calorie free originally approved in US Medical problems: loss of fat soluble vitamins anal leakage as it is not absorbed Fut enzymes are SPECIFIC to glycerol esters and are very efficient
Processing of Dietary Lipids in
Vertebrates
Bile salts emulsify dietary fats in the small intestine Pancreatic lipases degrade tiacylglycerols Fatty acids and other breakdown products are taken up by the intestinal muscosa and converted into triacylglcyerols Triacyclglycerols are incorporated with cholesterol and apoplipoproteins into chylomicros chylomicrons move through lymphatic system to tissue Lipoprotein lipases converts triacylglycerols to fatty acid and glycerol Fatty acids enter cell and are oxidized TERM 77
Pancreatic
Lipase
DEFINITION 77 Catalyzes TF --> 2MG + 2Fatty. products easily cross gut wall and are re-esterified Substrate (TG) Mixed with Food: Need lipid emulsion and proteases Lipid Emulsion - Required Bile salts works on lipid micelles. pH =7 is important for function. Bile salts change pH Requires Co-Lipase bind to lipase, contacts substrate, opens lid on lipase co-lipase opens active site on lipase to allow triglyceride in TERM 78
Bile Salts
DEFINITION 78
Steroidal nucleus with taurine that has ionic terminus on the
side. One side is hydrophobic whereas the other is
hydrophilicThe hydrophilic group on the outside surface
where the hydrophobic group is packed within the molecule.
The triglyceride can be in the hydrophobic interior
TERM 79
Classes of Lipoproteins
DEFINITION 79
Chylomicron --> ~85% tiacylglycerolsVLDL --> ~50%
triacylglycerols
both have core of triglycerides and cholesterol esters
both have shell with mono layer of phospholipids
both have the key recognition api-CII which activates
lipoprotein lipase
LDL ~ 10% triacylglycerolsHDL ~ 4% triacylglycerols
TERM 80
Chylomicron
DEFINITION 80
Surcae is a layer of phospholipids with heads facing the
aqueous phase. It is sequestered into the interior to make up
80% of mass. Apolipoproteins that protrude from surface act
as signals in the uptake and metabolism of chylomicron
contents. Apo-CII targets particles such that it can interact
with lipoprotein lipase later on
LDL
Similar to chylomicron but the core in enriched with many
more cholesterol esters and less triglyceridesBoth
cholesterols and cholesterol esters are hydrophobic with one
polar head group
TERM 82
Lipoprotein
Lipase
DEFINITION 82
Works on TG in lipoproteins (chylomicrons and VLDL).
They both have C2 recognition whereas LDL and HDL do
not so they cannot be worked on
located in peripheral tissues, adipose tissues, and muscle
apo-CII is a recognition protein in lipoprotein particle
recognized by Lipoprotein Lipase
TERM 83
Lipoproteins and Lipid Transport
DEFINITION 83 Exogenous Pathway lipids are packaged into chylomicrons where much of ticlygerol content is released by lipoprotein lipase to adipose and muscle chylomicron remnants are taken up by liver bile salts prouced in liver aid in dispersing dietary fats Endogenous pathway packaged in liver and liver in peripheral tissue by VLDL extraction of lipid form VLDL to LDL occurs to deliver cholesterol to extrahepatic tissue Excess cholesterol in tissue is transported to liver in HDL TERM 84
Hormone Sensitive Lipases
DEFINITION 84 Enzyme Names (all close to lipid vacuole): Adipocyte Triacylgycerol Lipase: TG --> DG + FA Hormone Sensitive lipase (HSL) DG --> MG + FA Monoacylglycerol Lipase (MGL): MG --> Glycerol + FA Regulation: by glucagon which causes cAMP/PKA mediated events Perilipin and CGI which access lipases on surface of lipid Fates of ProductsFatty acids released are carried by albumin to liver and muslce, Glycerol enter blood stream as it is not converted to Gly-3-P TERM 85
Regulation of Hormone Sensitive Adipocyte
Lipases
DEFINITION 85 Hormone (glucagon or epinephrine) bind the receptor and triggers transduction events with generate cAMP and PKA PKA phosphorylated perilipin peripilin dissociates from coactivator CGI Coactivator activates first lipase AGTL generating DG and FA PKA activates HSL to generate MG and FA MGL converts MG to glyceral and fatty acid glycerol leaves adipocyte since no glycerol kinase to convert to Gly-3-P and is exported to muscle/liver on albuminator and recoiled into TG in adipocyte
Carnitine Transport System
Carnitine acyltransferase I transfers the fatty acyl group from fatty acyl CoA to carnitine Pores - created by porin - in outer mito membrane allows the adduct to freely pass into the inter membrane space Carnitine transporter exchanges the fatty acyl carnitine with free carnitine Carnitine acyltransferase II in the matrix regenerates fatty acyl CoA thereby freeing carnitine inside the mito Fatty acyl CoA enters beta oxidation TERM 92
Role of Carnitine
DEFINITION 92
(COO- attached at right)
to carry fatty acyl group across inner mito membrane
fatty acid is committed to beta oxidation
carnitine is specific for long chain fatty acids (not used for
C5-C10)
TERM 93
Human Carnitine Deficiency
DEFINITION 93 Caused by genetics and can be:Systematic: all organs --> low carnitine everywhere, no ketone bodiesMytopathic: just muscle, fat build up in liver, normal ketogenesisSymptoms: Lethargy, Fat accumulationTreatment: carnitine supplements, medium chain fatty acidsThe deficiency teaches us: carnitine is synthesized in body carnitine is needed for beta oxidation and ketogensis no carnitine = fat in liver and muscle TERM 94
Beta Oxidation
DEFINITION 94 Dehydrogenation of fatty acyl CoA produces a double bond (trans) between the alpha and beta carbon. FADH2 is released. Acyl-CoA dehydrogenase catalyzes this (oxidation) Water is added to double bond by enoyl CoA hydrates to get a L- hydroxy molecule (hydration) Alcohol is dehydrogenase by beta hydroxylacyl CoA to get a ketone and NADH (oxidation) Thiolase doesreaction with Coenzyme A that produces a fatty acid and acetyl CoA so for C16 we get 8 acetyl CoA for CAC (cleavage) TERM 95
Fates of NADH and FADH
DEFINITION 95
They both enter the ETCNADH gives 2.5 ATPFADH2 gives 1.
ATP
Regulation of Beta Oxidation
malonyl CoA blocks carnitine transport system thereby
rending beta oxidation useless
A high energy charge blocks beta oxidation
NADH inhibits 3 hydroxyacyl CoA dehydrogenase
Acetyl CoA inhibits thiolase
TERM 97
Fatty Acid Synthesis
DEFINITION 97
Acetyl CoA carboxylase regulates the pathway
allosterically
levels of this are unregulated by low fat diets
TERM 98
Peroxisomal Beta Oxidation
DEFINITION 98
occurs in peroxisome
exists to shorten very long chain fatty which then can
undergo beta oxidation in the mitochondria
it has the same 4 steps as mito oxidation HOWEVER to
ETC is there instead it uses catalyze to oxidize FADH
NADH and Acetyl Coa re exported from the peroxisome to
process
TERM 99
Omega Oxidation
DEFINITION 99 occurs in endoplasmic reticulum starts with omega carbon likes 10-12 carbons progressive oxidations at omega carbon release succinate and adipate these products are fed into beta oxidation and can be metabolized at either end first step is done is cytochrome 4500 and uses NADPH and O and NADH is generated in the next two oxidation that hydroxylate or demethylate steroids TERM 100
Anaplerotic Reactions - Liver
DEFINITION 100 Pyruvate + HCO3 + ATP --> Oxaloacetate + ADP + Pi reversible catalyzed by pyruvate carboxylase Healthy --> liver is getting glucose fadn fatty acids from diet. Glucose provides pyruvate to replenish oxaloacetate which allows for beta oxidation to feed acetyl CoA into the cycleStarving --> no supply of oxaloacetate therefore the CAC comes to a halt. In response the Liver converts fatty acids from adipose tissues into acetyl CoA which goes to ketone bodies (ketogenesis)
