Exam #2 Flashcards
Carbohydrate Structure
(CH2O)n are aldehydes or ketones containing multiple hydroxyl (OH) groups.
Simple - mono and di-saccharides
Complex - oligo (3-10 sugar units) and polysaccharides (10+ sugar units)
Glycosidic Bonds
are how monosaccharides are joined to form oligo and polysaccharides
Glycoproteins & Glycolipids
CHO maybe complexed with proteins or lipids
Monosaccharides
glucose, fructose, galactose
Glucose
Principle source of energy
Glucose Structure
Glucose on Cell Surface
Recognition for communication purposes
Fructose
Monosaccharide - fruit, corn-syrup in processed foods
simple CHO
sweetest sugar
Fructose Structure
Galactose
monosaccharide
compare structure to glucose to identify
image of Beta D galactose
Pentoses
Monosaccharides Ribose (5C) and Deoxyribose comprise part of RNA and DNA
Ribitol - reductuction product of ribose, constituent of riboflavin and the flavin coenzymes; FAD and FMN
Disaccharides
lactose, sucrose, maltose
two monosaccharide units joined by convalent bonds
Lactose
Disaccharide - Milk
Made of glucose and galactose
simple CHO
can’t absorb stays in gut
Lactase
enzyme that breaks down lactose
beta - hard to break down in body you need lactase enzyme in order to do so
Sucrose
Disaccharide - Table sugar, cane, and beet sugar
made of glucose and fructose
simple CHO
2nd sweetest sugar
Maltose
Disaccharide - Beer and malt liquors
made of glucose and glucose
simple CHO
doesn’t normally occur naturally
brush border digests
formed from hydrolysis of starch
Oligosaccharides
3-10 sugar units
raffinose, stachyose, and veracose
complex CHO
attaches monosaccharides via acetal (glycosidic bonds) to form short chain polymers
Formed between OH group of one sugar unit and OH group of next with elimination of water (condensation)
can be alpha or beta based on anomeric carbon before bond was formed
not common - disaccharides are more common
Polysaccharides
>10 sugar units
starch, glycogen, dietary fiber
complex CHO
Homopolysaccharide
structure is composed of a single type of monomeric (monosaccharides) unit
in greater abundance than heteropolysaccharides
Heteropolysaccharides
two or more different types of monosaccharides make up its structure
Starch
Polysaccharides (more than 10 sugar units) - (amylose and amylopectin)
wheat, rice, corn, barley, oats, legumes, breads, cereals, legumes
Starch is storage form of CHO in plants.
made of glucose
Complex CHO
ALL starch is ALPHA LINKAGE
Amylose
starch (breads, cereals, and legumes)
linear, unbranched structure
15-20% of total starch content
alpha-1-4 glycosidic linkage
Amylopectin
starch (breads, cereal, legumes)
80-85% of total starch content
branched chain polymer
alpha-1-6 glycosidic linkage makes branch point linkage
alpha-1-4 glycosidic linkage connects glucose units
requires 2 enzymes to breakdown due to different linkages
high degree of branching but not as much as glycogen
provides a large number of nonreducing ends from which glucose residues can be cleaved and used for energy
Glycogen
Polysaccharide (more than 10 sugar units)
human made in the skeletal muscle and liver
Glycogen is storage form of CHO in aminals.
made of glucose
Complex CHO
highly branched is most effective attracts less water and more enzymes can work on it
can be hydrolyzed from nonreducing ends of glycogen chains
provides a large number of nonreducing ends from which glucose residues can be cleaved and used for energy by entering into energy releasing pathways
Dietary Fiber - Cellulose
homopolysaccharide (glucose) - rough part of grains and fruit
provides structure in the cell walls of plants
dietary fiber - bulking agent and energy souce for bacteria
considered dietary b/c can’t be digested by mammals
contains beta-1-4 glycosidic linkage therefore resistant to digestive enzyme alpha-amylase which favors alpha-1-4 linkages
Chiral Carbon
has 4 different atoms or groups attached
D Isomeric Forms
OH group is to the right
all naturally occurring sugars are D
enzymes are specific and will only work on D or L NOT BOTH
L Isomeric Forms
OH group of the chiral C is to the left
enzymes are specific and will only work on D or L NOT BOTH
Anomeric Carbon
The carbon that forms a ring structure with the reducing carbon reacting with OH group on the highest numbered chiral carbon of monosaccharide.
the carbon atom comprising the carbonyl function
anomeric carbon is the new asymmetric center
Alpha
FORM: when OH group of anomeric carbon is drawn below the plane of ring
DOWN
Starches - soluble and easily digested
LINKAGE: (disaccharides)
Humans can digest alpha because enzyme is made to support alpha linkage.
straight
Beta
FORM: when OH group is above the plane of the ring
UP
Fiber (can’t digest-only animals and bacteria)
Cellulose formed when synthesized from beta-glucose units is INSOLUBLE and cannot be digested as a food source by most animals
LINKAGE: (disaccharides)
zigzag
Polysaccharide Digestion
Mouth - salivary alpha-amylase hydrolyzes alpha-1-4 linkages
amylose->dextrins amylopectin->dextrins
Stomach no digestion pH too low inactivates enzyme
Small intestine - pacreatic alpha-amylase hydrolyzes alpha-1-4 linkage; bicarbonate in duodenum elevates pH
dextrins-> maltose dextrins->maltose and limit dextrins
Brush Border of SI (disaccarides)
amylose - maltose (maltase) -> glucose
amylopectin - maltose (maltase)-> glucose
limit dextrins (alpha-dextrinase) -> glucose
Resistant Starches
crystalline starch is insoluble in water and nondigestible
when heated becomes digestible but upon cooling reverts back
starches can be chemically modified to resist digestion by increasing crosslinking between chains
Disaccharide Digestion
Mouth - no digestion
Stomach - no digestion
Upper Small Intestine - microvilli of the intestinal mucosal cells (enterocytes) the brush border
enzymes located on enterocytes lactase, sucrase, maltase, and isomaltase
lactose (lactase catalyzes clevage) ->galactose & glucose
sucrose (sucrase hydrolyzes) -> glucose & fructose
maltose (maltase hydrolyzes) -> glucose & glucose
Isomaltose (isomaltase or alpha-dextrinase from amylopectin hydrolyzes alpha-1-6 linkage) -> glucose & glucose
Absorption - enterocyte to blood
once food is digested nutrients must move into the cells of the GI tract by the process absorption
The wall of the small intestine is composed of absorptive mucosal cells that line projections called villi that extend into the lumen.
On the villi are absorptive cells (enterocytes) that have microvilli (brush border)
diffusion - particles move from high to low concentration
facilitated diffusion-carrier want equalization of substance each side of membrane
active transport-concentration only on one side. requires ATP and Na+. one directional carriers
pinocytosis- large molecules cell membrane engulfs
Absorption of Glucose & Galactose
Into CELL: Active Transport - SGLT1 (sodium glucose transporter 1) uses ATP to transport sugar through mucosal cell. 1 glucose and 2 Na+ are transported into mucosal cell of the SI at one time. carrier used to cross cell membrane
Into BLOOD: Diffusion GLUT2 transports glucose from the intestinal mucosal cell (enterocyte) into the portal blood. dependent on blood glucose concentration
Absorption of Fructose
Into CELL: facilitated transport - GLUT5 fructose transported into the mucosal cell of SI
Into BLOOD: GLUT2 factilitated transport fructose transported from the mucosal cell of SI
absorbed by the liver where it is phosphorylated and trapped (no fructose in blood)
limited in 60% of adults
fructose absorption is slower than glucose and galactose
Transport
going from blood to other tissues
Galactose and Fructose Transport
transport across the wall of intestine into portal circulation
portal circulation -> directly to liver (major site of metabolism) through specific hepatocyte receptors
enters liver cells by facilitated transport and metabolized
converted to glucose derivatives and have same fate as glucose
in liver-> converts to glucose-> stored as glycogen or catabolized
Glucose Transporter (GLUT)
glucose is highly polar
cell (lipid bilayer) membrane is nonpolar matrix
the family of integral protein carriers involved in this process are glucose transports (GLUT)
glucose enters cell through these proteins that are embedded within cell membrane. FACILITATED DIFFUSION
these integral proteins (12) have specific combining site
these proteins undergo conformational change upon molecule binding which allows the molecule to be TRANSLOCATED to the other side of the membrane and released
can reverse this conformational change when molecule is unbound so that the process can be repeated
Insulin - Cellular Absorption
insulin - anabolic hormone involved in glucose synthesis and storage released by Beta-cells of pancreas
role in cellular glucose uptake
binds to membrane receptor
stimulates GLUT4 to move to membrane
Maintains blood glucose levels
insulin receptor in mucles and liver
muscles=use
liver=store
- ) stimulates uptake of glucose by muscle and adipose
- ) Inhibits the synthesis of glucose (glyconeogenesis)
The rise in blood glucose following a CHO meal triggers release of insulin while reducing the secretion of glucagon.
Insulin Receptor
doesn’t take glucose into cell
insulin - anabolic hormone involved in glucose synthesis and storage
insulin -> receptor -> 2nd messenger (signal) -> stimulates uptake of glucose -> to glycogen to store or
insulin binds to it’s receptor intracellular domain changes shape which cause chain of reactions that activate certain enzymes.
more glucose transporter proteins are released from intracellular stores and move to the plama membrane and become embedded
GLUT4
insulin regulated
GLUT4 concentration on plasma membrane increases in response to the hormone insulin
more membrane transporters = increase in glucose uptake
skeletal muscle and adipose tissue are responsive to insulin
muscle, heart, brown and white adipocytes
GLUT3
high affinity glucose transporter with expression in those tissues that are highly dependent on glucose
Brain
Glucose Distribution
muscles, kidney, and adipose
kidney - liver can’t filter glucose out not suppose to have C units in urine diabetes= sweet urine kidney damage
uptake of glucose by skeletal and adipose tissue are insulin dependent (GLUT4)
uptake by liver is insulin independent
Glycemic Response to Carbohydrates
the rate glucose is absorbed from intestinal tract is important in controlling the homeostasis of blood glucose, insulin release, obesity, and possible weight loss.
Glycemic Index
increase in blood glucose level over the base-line level during a 2 hour period following consumption of a defined amount of carbohydrate (usually 50 g) compared with the same amount of CHO in a reference food
high glycemic food cause a spike in bld glu levels
low glycemic food not as bad of a spike
PTN and FAT slow digestion
Glycemic Load
Glycemic load = glycemic index X g of CHO in a serving
High GL = increase bld glu
takes into account that we don’t just eat single food but meals made up of a number of foods
Metabolic Pathways of Carbohydrate Metabolism
glycogenesis - making glycogen
glycoenolysis - breakdown glycogen
glycolysis - oxidation of glucose
gluconeogenesis - produce glucose from nonCHO intermediates
hexose monophosphate shunt - production of 5C monosaccharides from NADPH
TCA - oxidation of pyruvate and acetyl CoA
Glycogenolysis
The pathway by which glycogen is enzymatically broken down to individual glucose units in the form of glucose-1-phosphate
hormone regulated
- glucagon (pancreas)
- epinephrine (adrenal medulla)
both hormones function through the second messenger cAMP which regulates phosphorylation state of enzymes
phosphorolysis- glycogen glycosidic bonds are cleaved by adding a phosphate
reaction is catalyzed and regulated by glycogen phosphorylase (muscle and liver)
Glycogenesis
conversion of glucose to glycogen (insulin stimulates)
important in hepatocytes bc **liver **(maintaining glucose homeostasis) is major source of glycogen synthesis and storage
other major site of storage is skeletal muscle (used for energy) and to a lesser extent also adipose tissue
4 Fates of Glucose
- Glycogen Synthesis - (Glycogenesis) reversible
stimulated by high glucose (liver), insulin, low glycogen (muscle)
- ATP Synthesis - produce energy NOT reversible
Glycolysis - low energy produced, cytoplasm, anaerobic
glucose -> pyruvate releases ATP
Anaerobic Glycolysis = 2 ATP/glucose and maintain blood glucose. pyruvate to lactate
RBCs, WBCs, kidney medulla, enterocytes, lens, cornea, skin, and skeletal muscle (rely on glycolysis bc lack mitochondria)
Aerobic Glycolysis = 38 ATP/glucose and maintain blood glucose
glucose->pyruvate->acetyl-CoA->TCA
brain, liver, skeletal muscle, kidney cortex
TCA - high energy produced, mitochondria, aerobic
upon completion of acetyl-CoA through TCA -> lots of ATP!!
Stimulated: high glucose, low ATP, insulin
Inhibition: high ATP, FFAs
- FFA Synthesis - fatty acid production NOT reversible (only occurs if excess calories are consumed)
Acetyl-CoA->FFA synthesis->TG (liver and adipocytes)
Stimulated: high glucose, high ATP, and insulin
- NEAA Synthesis - amino acids reversible
Glycolysis
glucose degraded into 2 pyruvate
Anaerobic -> pyruvate to lactate from muscle can then move to the blood stream and be carried to the liver for conversion into glucose. releases only small amount of energy to help sustain muscles
Aerobic -> pyruvate transported to mitochondria goes through TCA completely oxidized to CO2 and H2O and ATP
notes: pyruvate->acetyl CoA->TCA->electrons enter ETC=ATP
Glycolysis: Step 1
Glucose phosphorylated to Glucose-6-Phosphate
Enzymes: glucokinase (Liver) and hexokinase (liver or other tissues)
Rate-limiting step - 1 ATP consumed
irreversible (unless use G-6-phosphotase in liver) liver isn’t selfish will return glucose back to blood
glucokinase and G-6-phosphotase enable the liver to regulate blood glucose levels
adding phosphate traps glucose into cell (when BGL are high)
hexokinase is inhibited by G6P competes for active site and by allosteric interactions at a separate site on enzyme
glucokinase has high km for glucose (prevents too much glucose being removed from blood). only active at high glucose. not inhibited. allows glucose to be stored at glycogen in liver only when blood glucose is high
ATP-> ADP
Phosphate added to glucose-6-phosphate
Glycolysis: Step 2
G6P isomerized to Fructose-6-phosphate
Enzyme: phosphoglucose isomerase
smaller ring but still 6 carbons
Glycolysis: Step 3
F6P phosphorylated to fructose-1,6-bisphosphate
Enzyme: catalyzed by phosphofructokinase (PFK)
Irreversible - Rate limiting
allosteric Inhibitors: ATP, citrate, certain FA, increase in blood concentration of H ions
Activators: AMP, ADP, and fructose 2,6-bisphosphate produced from fructose 6-P using enzyme phosphofructose kinase 2 (PFK2)
low ATP speeds reaction up
ATP -> ADP
phosphate added to fructose-1,6-bisphosphate
Glycolysis: Step 4
F 1,6 bisP into glyceral dehyde-3-phosphate (G3P) and dihydroxyacetone (DHAP)
Enzyme: aldolase
G3P and DHAP are each 3C units
Glycolysis: Step 5
DHAP is converts to G3P
Enzyme: triosephosphate isomerase
G3P = glyceraldehyde-3-phosphate
Glycolysis: Step 6
G3P is oxidized and phosphorylated to 1,3-bisphosphoglycerate
enzyme: G3-P dehydrogenase
requires NAD and inorganic P
produces NADH (energy producing)
NADH = 3ATP
Glycolysis: Step 7
1,3-bisphosphoglycerate to 3-phosphoglycerate
enzyme: phosphoglycerate kinase
substrate level phosphorylation
2 ATPs produced from 1 glucose
Net ATP=0
ADP -> ATP
phosphate removed from 1,3-bisphosphoglycerate
Glycolysis: Step 8
3-phosphoglycerate to 2-phosphoglycerate
Enzyme: phosphoglycerate mutase
reversible
phosphate group transfer from carbon 3 to carbon 2
Glycolysis: Step 9
2 phosphoglycerate to phosphoenolpyruvate + H2O
enzyme: enolase
Dehydration rxn
reversible
forms a double bond between the 2nd and 3rd C
Glycolysis: Step 10 RLR
phosphoenolpyruvate (PEP) to pyruvate
enzyme: pyruvate kinase (PK)
transfer of phosphate from phosphoenolpyruvate (PEP) to ADP
substate level phosphorylation
IRREVERSIBLE
net yields 2 ATPs per glucose molecule
PK inhibited by ATP and alanine
PK activated by Fructose 1,6 bisphosphate
PK is regulated by covalent phosphorylation inhibited by phosphorylation
ADP -> ATP
phosphate removed from 2nd Carbon
Glycolysis: Step 11
pyruvate to lactate
enzyme: lactate dehydrogenase
under anaerobic conditions (fermentation)
NADH+ and H+ have 2H and electrons removed and given to pyruvate
NADH->NAD
NAD formed from this reaction can replace NAD needed in step 6 of glycolysis
RLR Rxns
3 enzymes catalyze highly spontaneous rxns
- hexokinase
- phosphofructokinase (PFK)
- pyruvate kinase
control of these enzymes determines the rate of glycolysis
IRREVERSIBLE RXNs
Glycolysis ATP counting
Glucose
step 1 use 1 ATP = -1
step 3 use 1 ATP= -2
step 6 gain NADH (3 ATP) per G3P = 2 NADH
step 7 gain 2 ATP = 0
step 10 gain 2 ATP per glucose = 2
Pyruvate
step 11 (anaerobic) use NADH (-3 ATP) = -2 NADH
NAD too big to leave cytosol need shuttle system
glucose + 2NAD + 2ADP + 2P ->
2 pyruvate + 2NADH + 2 ATP
Shuttle Systems
NADH (hydrogens and electrons) produced by glycolysis cannot enter mitochondria directly in order to be oxidized by ETC
- Malate - Aspartate shuttle system
liver, kidney, and heart
2 NADH from glycolysis = 6 ATPs + 2 ATP from glycolysis = 8 ATPs
- G3P shuttle system (dominate)
brain and skeletal muscle
2 NADH from glycolysis -> 2 FADH2 = 4 ATPs + 2 ATP from glycolysis = 6 ATPs
Location Change
glycolysis is in cytosol of cell
pyruvate goes to mitochondrion to be further metabolized
inner membrane of mitochondria permeability barrier
matrix contains pyruvate dehydrogenase of TCA
Pyruvate to Acetyl-CoA
3C -> 2C + CO2
enzyme: pyruvate dehydrogenase (PDH)
oxidative decarboxylation of pyruvate
produce NADH and CO2
NADH = 3 ATPs
IRREVERSIBLE - acetyl CoA is also produced from fatty acids (no fatty acid to glucose possible)
Important bc ready for TCA and fatty acid synthesis
Regulated by Inhibition
NADH competes with NAD for E3 binding
Acetyl CoA competes with CoA for E2 binding
TCA Cycle
presence of oxygen
pathway for oxidation of amino acids, fatty acids, and carbohydrates
6C goes CO2 -> 5C goes CO2 -> 4C
3CO2 , 4NADH , 1 FADH2 , 1 ATP produced
1 NADH produced when pyruvate goes to acetyl CoA
TCA: Step 1
Acetyl CoA (2C) + Oxaloacetate (4C) + H2O -> Citrate (6C) + CoA
enzyme: citrate synthase
condensation rxn
TCA: Step 2
Citrate (6C) -> Isocitrate (6C)
enzyme: aconitase
isomerization
TCA: Step 3 RLR
Isocitrate (6C) + NAD -> Alpha-ketoglutarate (5C) + CO2 + NADH + H
enzyme: isocitrate dehydrogenase
oxidatve decarboxylation
Allosteric Enzyme
inhibited by NADH and ATP
activated by ADP
too much product then acetyl coa goes to fatty acid synthesis instead and entire pathway shutdown
NADH=3 ATPs
TCA: Step 4
alpha-ketoglutarate (5C) + NAD -> Succinyl-CoA (4C) + CO2 + NADH + H
enzyme: alpha-ketoglutarate dyhydrogenase
oxidative decarboxylation
NADH=3 ATPs
multienzyme complex composed of 3 subunits E1, E2, E3
requires CoA, NAD, TPP, Lipoic Acid, and FAD
Allosteric enzyme
inhibited by increased levels of succinyl CoA, NADH, ATP
TCA: Step 5
Succinyl-CoA (4C) + P -> Succinate (4C) + CoA
enzyme: succinyl-CoA synthetase
bond hydrolyzed energy released used for substrate level phosphorylation
GDP phosphorylated to GTP
require inorganic phosphate
GTP=1ATP
TCA: Step 6
Succinate (4C) + FAD -> Fumarate (4C) + FADH2
enzyme: succinate dehydogenase
oxidation rxn
enzyme is integral protein of inner mitochondrial matrix
SDH enzyme requires coenzyme
uses FAD instead of NAD
FADH oxidized in ETC to produce 2 ATPs
TCA: Step 7
Fumarate (4C) + H2O -> Malate (4C)
enzyme: fumarase
hydration rxn
lose double bond
TCA: Step 8
Malate (4C) + NAD -> Oxaloacetate (4C) + NADH + H
enzyme: malate dehydrogenase
oxidation rxn
NADH=3ATPs
TCA ATP Counting
acetyl CoA
step 3 NADH = 3 ATPs
step 4 NADH = 3 ATPs
step 5 GTP = 1 ATP
step 6 FADH2 = 2 ATPs
step 8 NADH = 3 ATPs
oxaloacetate
12 ATPs x 2 acetyl CoA = 24 ATPs
ETC
inner mitochondrial membrane
oxidative phosphorylation occurs
oxidation of a metabolite by oxygen
and
phosphorylation of ADP
Electron carries are substances that make up ETC
contain prosthetic groups which are either e- acceptors (oxidizing agent) or e- donors (reducing agent)
downhill flow of electrons
from NADH to FADH2 to O2
ETC Image
electrons pass in ETC
H+ are translocated to inner membrane space creating electrical charge and pH difference
Complex I - NADH + H to NAD electrons pass to CoQ and 4 H+ to intermembrane. enzyme: NADH dehydrogenase
Complex II - FADH2 to FAD electrons and hydrogens pass to CoQ. enzyme succinate dehydrogenase
CoQ transports electrons to Complex III
Complex III - H to intermembrane heme (Cu & Fe)
Cyt C transports electrons to Complex IV
Complex IV - reduces O2 to form H2O heme (Cu & Fe)
electrical change and pH difference provide driving energy
Complex V - ATP-synthase enzyme protein changes conformation results in ATP synthesis and movement of H back to mitochondrial matix
heme holds apart electrons until 4 are acheived then gives
Hexosemonophosphate Shunt
pentose phosphate pathway
purpose is to generate intermediates
Products:
- Pentose Phosphates - for DNA, RNA, and nucleotide synthesis
- reduced cosubstrate NADP to NADPH - reducing agent for biosynthesis of fatty acids and cholesterol
very efficient - recycling 2 ribose to fructose-6-phosphate to glucose
Gluconeogenesis
formation of glucose by liver or kidney from nonCHO precursors
purpose: maintain blood glucose level: fasting sustained excercise, stress, and hypoglycaemia
when glucose storage is low or tissue without mitochondria (anaerobic) rely on it (nerve cells and RBC)
pyruvate to PEP has to be done by OAA by pyruvate carbosylase
PEP to pyruvate by phyruvate kinase
lactate -> pyruvate (cyto) moves to mito
amino acids -> pyruvate or oxaloacetate in mito
glycerol -> DHAP -> G3P all in cyto
bypass irreversible steps in glycolysis to produce glucose
Pyruvate Carboxylase
pyruvate (3C) to OAA (4C)
step 1 of gluconeogenesis
allosteric enzyme postively regulated by Acetyl CoA
Pyruvate + HCO3 + ATP <-> OAA + ADP + P + H
elongation process
need bicarbonate
when low CHO pyruvate has to be from AAs, lactate, glycerol to make OAA needed for TCA
starvation, low CHO diet, infection, and trauma
glucose needed for anaerobic tissues brain RBC
CHO RDA
male or female 130 g/day
