biochem exam 3 Flashcards
(160 cards)
1
Q
what are the three factors that control metabolic homeostasis?
A
blood level of nutrient
hormone levels
nerve impulse (direct or via hormone release)
2
Q
what is epinephrine also known as?
A
adrenaline
3
Q
what are the insulin counter-regulatory hormones?
A
glucagon, epinephrine (norepinephrine), and cortisol
4
Q
what kind of hormone is insulin? what is its function?
A
an anabolic hormone
fuel storage, growth, and protein synthesis
5
Q
what makes skeletal muscle special in response to glucagon?
A
it is not affected by glucagon because it doesn’t have glucagon receptors
6
Q
where is insulin synthesized and secreted?
A
from beta cells of the pancreas and is synthesized a preproinsulin
7
Q
explain the significance of c peptide in insulin?
A
c peptide connects the a-chain to the b-chain of preproinsulin and is later cleaved. insulin is rapidly removed from the blood but c-peptide is not. c peptide is used to measure an estimate of pancreatic insulin secretion
8
Q
what does Glipizide do?
A
it is used to treat type II diabetes by closing the ATP dependent K+ channel leading to release of insulin
9
Q
where is glucagon synthesized?
A
in the alpha cells of the pancreas as preproglucagon
10
Q
what are the 4 methods of hormonal regulation?
A
- change substrate concentrations
- covalent, reversible modifications to enzyme structure
- change concentrations of allosteric regulators
these are fast
slow = change the expression level or degradation rate of the regulatory enzymes
11
Q
what does NADPH do?
A
it is responsible for biosynthesis and detoxification
12
Q
what does ribose 5-phosphate do?
A
it is responsible for nucleotide synthesis
13
Q
what are the products of oxidative PPP?
A
G6P is oxidized (by G6PD)–> produces 2 NADPH, Co2, and ribulose 5-phosphate
NADPH can be used for FA synthesis, glutathione reduction (regenerate GSH), and others (like detoxification)
14
Q
what happens in the nonoxidative phase?
A
5C sugar derivatives of ribulose 5-phosphate (xylulose 5-phosphate and ribose 5-phosphate) are used to generate glycolytic intermediates like F6P and GAP
15
Q
how many NADPH are produced from 1 G6P?
A
2
16
Q
why is the oxidative phase important?
A
it is the key pathway for generating NADPH in ALL cells and ONLY pathway for generating NADPH for cells that lack mitochondria or O2 (like RBCs)
17
Q
explain the oxidative phase pathway
A
G6P is converted to 6-phosphoglucono-delta-lactone via G6PDH and produces NADPH + H+ using NADP+
6-phosphoglucono-delta-lactone –> 6-phosphogluconate via glucolactonase (addition of H2O and makes H+) –> RIBULOSE 5-PHOSPHATE via 6-phosphogluconate DH (usses NADP+ to make NADPH and CO2)
18
Q
what is a respiratory burst?
A
response to infectious agents and other stimuli where phagocytic cells (like neutrophils) generate free radicals to destroy invading pathogens
process uses lots of NADPH and O2
19
Q
explain the respiratory burst process
A
uses O2 and NADPH via NADPH oxidase to make NADP+ and O2- which can be generated into H2O2 –> addition of Cl- can make HOCl while addition of Fe2+ will make Fe3+ and OH radical
ONOO- (with NO)
All these destroy the pathogen
20
Q
what happens when G6PDH is deficient?
A
cell has decreased ability to generate NADPH
RBC mostly affected because it will become susceptible to oxidative damage
21
Q
how does ribulose 5-phosphate convert to its 5C sugar derivatives?
A
isomerized to ribose 5-phosphate (used for nucleotide synthesis or nonoxidative phase)
epimerized to xylulose 5-phosphate (used in nonoxidative phase and KEY REGULATOR of gene transcription –> promoting lipogenesis)
22
Q
what is special about nonoxidative reactions?
A
they are reversible
23
Q
what is significant about the carbons in the nonoxidative phase?
A
they undergo carbon shuffling between the 5C derivates to make F6P or GAP
24
Q
what happens when nucleotides are needed and no NADPH is needed?
A
use GLYCOLYSIS to make F6P and GAP then run the NONOXIDATIVE phase backwards
G6P –> F6P –> F1,6BP –> DHAP and GAP
F6P and GAP –> ribose 5-phosphate
25
what happens when NADPH and nucleotide needs are balanced?
run OXIDATIVE phase and ISOMERASE
G6P (using 2 NADP+ to generate 2 NADPH and 2 CO2) --> ribulose 5-phospate (isomerase) --> ribose 5-phosphate
26
what happens when you need more NADPH than nucleotides?
run OXIDATIVE and NONOXIDATIVE phases, use F6P and GAP to generate more G6P for OXIDATIVE phase
G6P (2NADP+) --> ribulose 5-phosphate (isomerase) --> ribose 5-phosphate --> F6P and GAP
GAP --> F1,6BP --> F6P --> generate more G6P
27
what happens when you need NADPH and ATP?
run OXIDATIVE and NONOXIDATIVE phase, using the NONXOIDATIVE phase products for glycolysis
G6P (2 NADP+) --> ribulose 5-phosphase (isomerase) --> ribose 5-phosphate --> F6P and GAP
F6P --> F1,6BP --> DHAP or GAP ...--> 2 ATP and pyruvate
GAP ...--> 2 ATP and pyruvate
28
what inhibits G6PDH?
NADPH (feedback inhibition)
29
what causes the oxidative phase to run?
when [NADPH] is low and [NADP+] is high (feedback regulation)
30
how is the nonoxidative phase regulated?
because it is reversible, it is regulated by cellular concentrations of the pathway intermediates
31
what are the enzymes involved in the nonoxidative phase?
isomerase (like ribose), epimerase (like xylulose), and transaldolases and transketolases
32
what is special about transketolases?
they use TTP
thiamin deficiency is detected by measuring transaldolase and transketolase activities in RBC (activities are low --> can be increased by the addition of TTP = thiamine deficiency)
33
what is NANA also know as?
Sialic acid
34
what residue does type A blood group have?
GalNAc residue
35
what residue does type B blood group have?
Gal residue
36
what are gangliosidoses (sphinoglipidoses)
group of lysozomal storage disease resulting from defects in the degradation of gangliosides
37
how are gangliosidoses inherited?
autosomal recessive pattern and most present with neurological degeneration
usually fatal before early childhood (EXCEPTION of Gaucher disease)
38
what is Tay-Sachs disease?
beta-HeXosaminidase A deficiency (accumulation of gangliosides - GM2)
infantile onset with RAPID progression of neurodegeneration and blindness, CHERRY SPOT on macula
tA-saX
39
what is the Niemann-Pick disease?
accumulation of sphingomyelin (deficiency in sphingomyelinase)
infantile onset RAPID progression of neurodegeneration, CHERRY SPOT on macula, AND HEPATOSPLENOMEGALY
40
what is Gaucher disease?
beta-glucosidase deficiency
- commonly lysosomal storage disease, onset at any age (generally after childhood), NO NEURODEGENERATION, bone involvement (weakness with PATHOLOGIC FRACTURES and bone pain), HEPATOSPLENOMEGALY
GLUCOCEREBROSIDES accumulate in macrophages of liver, spleen, and bone
WRINKLED TISSUE PAPER
41
what are amino sugars synthesized from?
F6P which reacts with GLUTAMINE to form glucosamine 6-P and glutamate
42
what is I-cell disease?
Condition which PHOSPHORYLTRANSFERASE that makes MANNOSE-P is deficient --> mannose-P will NOT go to lysosome to be degraded and will instead be dumped into the cell and cause damage
lysosomal hydrolases are secreted from cell and INCLUSION BODIES FORM in lysosomes
43
what is the function of colipase?
facilitates the binding of TAG to the lipase active site
to catalyze digestion of triglycerides in the small intestine
44
what is the function of pancreatic lipase?
along with colipase, they catalyze digestion of TGs in SMALL INTESTINE
it hydrolyzes fatty acids from carbons 1 and 3 of TAG glycerol backbone (TAG-->DAG-->MAG)
45
how is cholesterol hydrolyzed?
dietary cholesterol comes in the form of cholesterol ester which MUST be hydrolyzed by cholesterol esterase
hydrolysis via cholesterol esterase for INTESTINAL ABSORPTION
46
what is significant about glycogen phosphorylase?
it catalyzes the PHOSPHOROLYSIS of glucose residues from NONREDUCING ends of the particle --> produces G1P
47
how are glycerophospholipids hydrolyzed?
hydrolyzed to form a free fatty acid chain and LYSOPHOSPHOLIPID using phospholipase A2
48
what happens to bile salts in lower concentrations?
they are water-soluble
49
what happens to bile salts at higher concentrations?
they are micelles
50
what is the critical micellar concentration (CMC) for bile salts?
5-15 mM
51
when are bile salts effective?
when the pH is higher than 4, bile salts will be deprotonated = effective emulsifiers
52
what happens when bile salts cannot efficiently emulsify dietary fats?
- decreased absorption of dietary fat
- decrease absorption of fat-soluble vitamins
- steatorrhea
52
what differs between chylomicrons and VLDL?
chylomicrons contain apoprotein B-48 while VLDL contain apoprotein B-100
53
where are TAGs and apoproteins synthesized?
TAGs are synthesized in the SER
apoproteins are synthesized in the RER
come together in the Golgi complex and then secreted into the lymph
enter circulation at thoracic duct
process takes about 1-2 hours
54
what does the formation of chylomicrons (in intestinal endothelial cells) and VLDL (in hepatocytes) depend on?
microsomal triglyceride transfer protein (MTP)
before leaving the ER, Apo48 and Apo100 have to associate with small amounts of lipids which is facilitated by MTP
deficiency in MTP leads to abetaliproteinemia
55
what does a deficiency in MTP cause?
abetalipoproteinemia (lack of beta lipoproteins in the blood)
can cause fat malabsorption, stearrohea, inability to absorb fat-soluble vitamins, inability to make FA storage in adipocytes and myocytes (impair gluconeogenesis) --> weight loss and less access to fat
treatment = low fat diet and supplements (fat-soluble vitamins = KADE, and essential fatty acids = a-linolenic acid, linoleic acid for plants and EPA and DHA for animals)
56
what is the function of ApoCII?
it activates lipoprotein lipase (LPL) which hydrolyzes chylomicron TAGS to 3 FA chains and glycerol so they can enter adipocytes and myocytes
deficiency in ApoCII will lead to elevated TG serum levels, chylomicron accumulation, and pancreatitis
attached to mature chylomicrons along with ApoE
57
where are mature chylomicrons attached?
to the luminal surface of capillary walls
where LPL is located
58
describe the order of chylomicron maturation
nascent chylomicron --> mature chylomicron --> chylomicron remnants
59
what is the function of metformin?
it inhibits complex I of ETC causing build-up of NADH --> unable to make ATP leading to decrease in ATP which activates pyruvate kinase and PFKL activity (liver isoform of PFK-1) --> AMP builds up and activates PFKL activity and inhibits FBP1 activity --> increases AMPK activation which improves glucose transport
inhibit gluconeogenesis
60
what is glifozins?
SGLT2 inhibitors
reduce glucose reabsorption in the kidney which leads to increase glucose excretion in urine and lowering blood glucose levels
61
what does bilirubin need to be bound to?
serum albumin --> transported to liver where it is conjugated with TWO glucuronates
it is also a DEGRADATION PRODUCT OF HEME
62
what is the cause of infantile jaundice?
low activity of HEPATIC BILIRUBIN GLUCURONYLTRANFERASE at birth
63
what are the two subunits of lactase synthase?
galactosyltransferase and alpha-lactalbumin
64
how is UDP-galactose synthesized from UDP-glucose?
via UDP-glucose 4-epimerase that requires NAD+
oxidizes C4 to KETONE, then reduced ketone back to ALCOHOL
65
where are O-linked carbohydrates synthesized?
in the ER directly on the PEPTIDE CHAIN
involves glycosyltransferase and occurs on SER/THR residues
66
where are N-linked carbohydrates synthesized?
in the ER directly on the DOLICHOL phosphate
oligosaccharide is then transferred to asparagine residues in target proteins and further processed in ER and GOLGI COMPLEX
attaches to ASN
67
what happens in the formation of mature chylomicrons to chylomicron remnants?
mature chylomicrons bind to LPL (attached to luminal surface of capillary walls)
ApoCII activates LPL --> catalyzes hydrolysis of triglycerides to 3 FA chains and glycerol which can then be taken up by adipocytes and myocytes
mature chylomicrons become chylomicron remnants (TG content decreases) and lose ApoCII proteins (increases exposure of ApoE on their surface)
68
who are more prone to G6PD deficiency?
men because the G6PD gene is on the long arm of the X chromosome
point mutations of G6PD can result in enzymes with decreased lifespan or decreased function
69
what is the most beneficial fat? followed by what?
omega 3 (from fish and plants like walnuts, canola oil, and flax seeds)
followed by omega 6 (corn, soy, safflower, and sunflower oils) and monounsaturated fats (olive, peanut oils, nuts, and avocados)
70
what does lingual and gastric lipase hydrolyze?
short and medium chain fatty acids from dietary TAGs
SCFAs and MCFAs can diffuse DIRECTLY INTO circulation (both come from dairy products, medium can come from coconut oil)
71
what is the significance of bile salts in TAG?
it prevents dietary TAGs in bile salt emulsion from accessing the active site of pancreatic lipase so colipase helps counteract this and facilitates the binding of TAG to lipase active site
72
what kind of chylomicrons are exocytosed into the lymph? where does it enter after?
nascent chylomicrons
enters circulation at the thoracic duct
73
what is produced from the hydrolysis of starch?
maltose and isomaltose also alpha dextrins and trisaccharides
74
what is the function of salivary alpha-amylase?
it breaks down starch into alpha-dextrins but cannot break down sucrose and lactose
glucoamylase can also break down alpha-dextrins
75
what are the insoluble and soluble fibers?
insoluble (cellulose, hemicelluose, and lignin)
soluble (pectins, gums, and mucilages)
76
ApoCII and ApoE come from....in the serum
HDL
they are transferred from HDL to nascent chylomicron to make mature chylomicron
77
what is the primary product of glycogenolysis in the liver and muscle?
G1P
78
what is PP1?
involved in glycogen metabolism and muscle contraction
hydrolyzes pyruvate kinase to active form
79
what are the benefits of dietary fiber?
anti-obesity (increase satiety by increasing GLP-1 and PYY--> decrease appetite, decrease lipogenesis (increase LIPE and FA oxidation, decrease TG accumulation, increase energy expenditure), anti-diabetes (increase satiety by increasing GLP-1 and PYY, increase insulin, decrease glucagon, increase glycogen synthesis, increase GLUT4)
anti-inflammation, hepatoprotection, neuroprotection, anticancer, cardiovascular protection, constipation treatment, immunoregulation, and inflammatory bowel disease treatment
80
both soluble and insoluble fiber can be fermented by gut microbes to form SCFAs (true/false)
true
81
what provides an accurate measure of pancreatic insulin secretion?
C-peptide
ex: normal about of C-peptide = normal amount of insulin
82
explain the release of insulin from the beta cells?
glucose enters the beta cells via GLUT2 transporters (passive transport) and is phosphorylated by glucokinase then enters glycolysis generating and increasing [ATP]
increase in [ATP] inhibits the ATP Dependent K+ channel which causes membrane depolarization and activates the voltage-gated Ca+ channel to allow Ca+ influx which triggers the exocytosis of vesicles containing insulin and c-peptide
83
what regulator can both stimulated insulin and glucagon release?
amino acids
84
what also expresses preproglucagon other than the alpha cells in the pancrease?
intestinal L cells
secrete GLP-1 and GLP-1 in response to entry of food into the intestine, GLP-1 stimulates insulin secretion and inhibits pancreatic glucagon secretion
85
Glucagon levels in diabetics remain...
elevated despite the high serum [glucose] because body thinks it's in the fasting/starved state since there's not enough insulin
86
What kind of receptor is the glucagon receptor?
GPCR
87
Explain the mechanism of glucagon action
glucagon binds to glucagon receptor and activates the G-alpha subunit by binding GTP and released the beta and gamma subunits --> GTP-G alpha S binds to and activates adenylyl cyclase increasing [cAMP] (cAMP activates cAMP-dependent kinase aka PKA) using ATP
Adenylyl cyclase then catalyzes the formation of cAMP --> cAMP phosphodiesterase converts cAMP into AMP
88
explain the mechanism of insulin action
insulin binds to the alpha subunits of insulin receptors which activates the tyrosine kinase on the beta receptors through autophosphorylation --> activated tyrosine kinase phosphorylates main target cytosolic proteins like insulin receptor substrate 1 (IRS-1) --> IRS-1 recognizes and binds to many signal transduction proteins (like phospholipase C - PLC and phosphadidylinositol 3-kinase - PI3 kinase)
89
how does insulin reverse glucagon-stimulated phosphorylation?
- inhibits adenylyl cyclase (to prevent more cAMP production)
- activates cAMP phosphodiesterase (lowers cAMP concentrations because high cAMP activates PKA which is activated by glucagon)
- dephosphorylates glucagon-activated proteins (often via phosphoprotein phosphatase 1 or PP1)
90
what is the insulin phosphorylation cascade mediated by?
PKB or Akt
91
what receptors activate G alpha s? what happens when it's activated?
beta receptors
stimulates formation of cAMP because it activates adenylyl cyclase
92
what receptors do epinephrine norepinephrine bind to?
adrenergic receptors
93
explain alpha 1 receptor
post-synaptic receptor that mediates vascular and smooth muscle contractions as well as GLYCOGENOLYSIS in LIVER, activates G alpha q (NOT a) which activates signaling pathway that increase [Ca+2]
94
what is the function of cortisol?
it is a hydrophobic hormone that can cross the cell membrane, regulates gene transcription
it upregulates the expression of enzymes in lipolysis and gluconeogenesis
long-term stress hormone
95
how is PFK-1 regulated by it's activators and inhibitors?
heteroallosterically
AMP and F26BP = activators
ATP and citrate = inhibitors
96
how is pyruvate kinase regulated?
by phosphorylation
glucagon is present = phosphorylates pyruvate kinase and inactivates it
pyruvate kinase activated when it's been hydrolyzed by PP1
pyruvate kinase is activated by F1,6BP and inhibited by ATP and LCFA (present in fasting)
97
why does the polyol pathway occur?
when there is an excess of glucose that the cell CANNOT metabolize then it can be converted to fructose --> sorbitol (GLUT 5 is a fructose transporter)
98
Explain the polyol pathway
D-glucose gets converted to sorbitol via ALDOSE REDUCTASE (uses NADPH) --> sorbitol gets converted to D-fructose via sorbitol DH (uses NAD+)
HOWEVER, sorbitol DH activity is low in tissues, causing build up of sorbitol which can lead to osmolar imbalance (cataracts, nephropathy, neuropathy), reduced ability to manage ROS because aldose reductase uses NADPH needed in detoxification --> makes cell susceptible to cellular oxidative damage
99
explain galactose metabolism
galactose is phosphorylated by galactokinase using ATP to produce galatose 1-P (build of galactose = nonclassical galactosemia)
galactose 1-P is converted to glucose 1-P via GALACTOSE 1-P URIDYLYLTRANSFERASE which depends on UDP-glucose (produces UDP-galactose which is substrate for epimerase that converts UDP-galactose to UDP-glucose) to react with galactose 1-P to make glucose 1-P (deficiency in galactose 1-P uridylyltransferase increase [galactose 1-P] causing classical galactosemia)
glucose 1-P is isomerized to glucose 6-P to be used in glycolysis or make glucose
100
explain galactosemia
defects in galactose metabolism can be detected in the first few days after birth
symptoms = vomiting, REFUSAL TO EAT, JAUNDICE, and cataracts
both nonclassical and classical galactosemia has build of galactose which will be converted to galactitol resulting in osmolar imbalance, cataracts, and KIDNEY DAMAGE (more common in babies than adults)
particularly in classical, galactose 1-P is very toxic to liver --> result in JAUNDICE and HEPATOMEGALY
101
when can you detect that a child has a defect in fructose metabolism?
occurs EXCLUSIVELY in the LIVER and not detected until after child begins to wean
102
what can hereditary fructose intolerance cause and what is it caused by?
causes SEVERE HYPOGLYCEMIA due to deficiency of aldolase B
can't convert F1P to glyceraldehyde (F1P is very TOXIC)
Because free phosphate is needed to run ATP synthase, it can't make ATP because the phosphate is stuck to F1P so no GLUCONEOGENESIS which means you can't break down glycogen leading to HYPOGLYCEMIA --> also means INHIBITS GLYCOGEN PHOSPHORYLASE in glycogen metabolism
103
what are the symptoms and causes of essential fructosuria?
patients are asymptomatic
caused by deficiency in fructokinase to convert fructose to F1P which is not as severe because no build up of toxic F1P
this is similar to nonclassical galactosemia
104
what is special about fructose metabolism?
it bypasses PFK-1
105
how does lactate dehydrogenase work?
involved in anaerobic glycolysis or when NADH/NAD+ ratio is high (can lead to lactic acidosis)
pyruvate (using NADH) --> lactate
when NADH/NAD+ ratio is low
lactate (using NAD+) --> pyruvate to feed back into glycolysis and the TCA cycle to make more NADH and ATP for ETC
NO NADH TRANSPORTERS, uses a malate-aspartate shuttle to transport NADH from OAA out of mitochondria
106
what happens during high intensity exercise?
the muscle's need for ATP exceeds the rate at which TCA and ETC can generate ATP so [AMP] begins to rise
AMP activates PFK-1 stimulating glycolysis
increasing the NADH/NAD+ in the cytosol drives the lactate DH reaction toward lactate (can be used in gluconeogenesis, other tissues like the heart can convert lactate to pyruvate then acetyl CoA which is 80% fate of lactate)
107
what is the cori cycle?
glucose from the liver during gluconeogenesis can be converted to lactate in RBC via anaerobic glycolysis --> lactate can be used by liver for gluconeogenesis
108
what are the 3 most important, regulated enzymes in gluconeogenesis?
PEPCK, F1,6Pase, and G6Pase
108
how can lactic acidosis occur?
may be caused by lack of oxygen (HYPOXIA, COPD, MI, and stroke) --> increase anaerobic glycolysis
also by inability of the liver to use lactate for gluconeogenesis (occurs when liver is metabolizing large amounts of alcohol increasing NADH/NAD+ ratio)
108
how is lactate transported?
via monocarboxylate transporters which also exports a proton --> high serum lactate levels will decrease pH because of its cotransport of H+
108
what happens in the conversion of pyruvate to PEP?
pyruvate that comes from lactate, alanine, and other AA is converted to OAA via pyruvate carboxylase (uses BIOTIN, CO2, and ATP)
OAA from the TCA cycle is converted to PEP via phophosenolpyruvate carboxykinase (PEPCK) using GTP and producing CO2 (NO NADH)
108
what are the non-carb precursors for gluconeogenesis?
glycerol, amino acids, propionyl CoA, and lactate (fructose and galactose are also considered glucogenic)
109
what happens when a person consumes an excessive amount of egg whites?
can lead to multiple carboxylase deficiency aka B7 (biotin) deficiency
109
where is PEPCK found?
in MITOCHONDRIA and CYTOSOL
110
how is OAA transported out of the mitochondria?
using malate or aspartate
111
what is pyruvate carboxylase activated by?
high acetyl CoA
112
Explain lipolysis and its function in gluconeogenesis
glucagon stimulates lipolysis which provides FA for beta-oxidation --> high [NADH] and [acetyl CoA] inhibit pyruvate DH complex (which uses TTP, along with a-kg DH), preventing formation of acetyl CoA from pyruvate allowing gluconeogenesis
113
what are the anaplerotic reactions in gluconeogenesis?
glucogenic amino acids can enter the TCA cycle at OAA (aspartate), succinyl CoA (propionyl CoA from valine and isoleucine and odd-chain FA), and alpha-ketoglutarate (glutamate)
114
how is PFK-1 bypassed in gluconeogenesis?
using F1,6Pase (FBPase-1)
HYDROLYSIS RXN no ATP is made
115
when can gluconeogenesis be stimulated?
during exercise, high-protein diets, and stress
116
how is gluconeogenesis regulated in short-term?
by substrate availability and glucagon/insulin
- acetyl CoA activates pyruvate carboxylase
- cAMP inhibits pyruvate kinase (because high cAMP activates PKA which will phosphorylate pyruvate kinase to the inactive form - think back to the diagram for pyruvate kinase)
- F26BP levels regulate this step (low levels will activate gluconenogenesis and FBPase-1 and PFK-1 is inactive)
- FBPase-1 is allosterically inhibited by F26BP and AMP and activated by ATP
117
how is gluconeogenesis regulated in long-term?
G6Pase, F1,6BPase, and PEPCK expression are induced by glucagon, epinephrine, and cortisol (long-term)
this may induce hyperglycemia as there will be more beta oxidation and more gluconeogenesis
118
where is the only glucose residue that is reducing attached to?
glycogenin
119
what is the structure of glycogen?
alpha 1-->4 bonds with alpha 1-->6 branches
120
why is the branching on glycogen important?
it provides many binding sites for enzymes that synthesize and degrade glycogen and ENHANCES ITS SOLUBILITY
121
how is glycogen synthesized?
glucose is convert to G6P via hexokinase or glucokinase
G6P is converted to G1P via phosphoglucomutase
G1P is converted to UDP via UDP-glucose pyrophosphorylase
4:6 TRANSFERASE (branching enzyme, transfers to another chain via alpha 1,6 linkage, every 7-9 residues) and glycogen synthase convert UDP-glucose into glycogen
process occurs during glycolysis and high glucose concentrations
122
how is glycogen degraded?
glycogen is converted to G1P via the debranching enzyme but prior to this chains are shorted within 4 residues of branch point (4:4 PHOSPHORYLASE, transfers 3 residues to end of nearby chain leaving branching glucose which gets cleaved by alpha 1,6 glucosidase), and glycogen phosphorylase
10% of glycogen is released as free glucose and 90% is converted to G1P --> G6P (can enter other pathways like glycolysis and PPP) --> glucose
123
why is G1P important?
it is the substrate for glycogenesis and product of glycogenolysis
124
where is glucose added in glycogenesis?
ONLY to the nonreducing end
125
how many G1P is produced per 1 glucose?
1 glucose for every 7-9 G1P
126
where is G6Pase present?
ONLY in LIVER and KIDNEY
involved in glycogenolysis and also catalyzes last step in gluconeogenesis
deficiency results in von Gierke's disease (types 1a, 1b, and 1c)
MUSCLES DO NOT HAVE G6PASE OR GLUCAGON RECEPTORS
127
what are the types of glycogen storage diseases?
Von Gierke - deficiency of G6Pase (type 1a) or associated transporters
Pompe - deficiency of lysosomal ALPHA 1,4 GLUCOSIDASE (appears normal at birth but over time lysosomes will fill up with junk and start experiencing symptoms) - LYSOSOMAL STORAGE DISEASE
Cori - deficiency of debranching enzyme
McArdle - deficiency of muscle glycogen phosphorylase
128
what are common symptoms for the glycogen storage diseases?
Von Gierke - Fasting hypoglycemia and lactic acidosis
Pompe - Cardiomegaly, hypotonia, lysosomes
Cori - Branched molecules found in the liver during biopsy or autopsy
McArdles - Exercise, red/brown urine (rhabdomyolysis)
129
what happens to the glycogen stores in muscle?
blood: increase epinephrine
tissue: increase AMP
increase Ca2+-calmodulin
increase cAMP
130
what are glycogen phosphorylase and synthase regulated by?
phosphorylation
when phosphorylase is phosphorylated it is ACTIVE
when synthase is phosphorylated it is INACTIVE
regulated ALLOSTERICALLY
131
what stimulates glycogenolysis?
epinephrine in the liver and MUSCLE
glucagon in the liver
glucagon binds to glucagon receptor, epinephrine binds to beta-2 adrenergic receptors --> both activate G alpha s
adenylyl cyclase is then activated producing cAMP which activates PKA --> PKA phosphorylates glycogen synthase (inactive) and phosphorylase kinase (active) which will then phosphorylate glycogen phosphorylase (active)
132
how does insulin reverse pathways stimulated by glucagon and epinephrine?
high intracellular [glucose] ALLOSTERICALLY simulated dephosphorylation of phosphorylase a (IN LIVER ONLY)
insulin-receptor tyrosine kinase cascade activates PP1 (hydrolyzes pyruvate kinase to active form) --> insulin receptor tyrosine kinase cascade activates cAMP phosphodiesterase
133
what is another receptor that epinephrine can bind to?
it can also bind to alpha-adrenergic receptors in the LIVER
alpha-adrenergic receptors activate Gqs which stimulates an increase in intracellular [Ca2+] --> stimulates glycogenolysis and inhibits glycogenesis
134
what kinases regulate glycogen synthase?
protein kinase C, calmodulin-depedent protein kinase, and phosphorylase kinase
ALL OF THESE KINASE INACTIVATE GLYCOGEN SYNTHASE (phosphorylase kinase activates glycogen phosphorylase)
Ca2+-calmodulin activates Calmodulin-dependent protein kinase and phosphorylase kinase
135
explain muscle glycogenolysis during exercise
- increased [AMP] ALLOSTERICALLY activates glycogen phosphorylase B
- Ca2+ is released and binds calmodulin and activates phosphorylase kinase
- binding of epinephrine to beta-adrenergic receptors stimulates PKA activating phosphorylase a
136
what is important about myocytes in glycogenolysis?
they LACK GLUCAGON RECEPTORS AND G6PASE --> will NOT release glucose in fasting state
glycogen stores are only for their cell use
137
what is produced from the oxidative phase of PPP?
2 NADPH (used to detoxify, for biosynthesis, and to reduce glutathione), CO2, and ribulose 5-P
138
what is produced in the non-oxidative phase of PPP?
ribulose 5-P is converted to its derivatives to generate glycolytic intermediates like G6P to feed into the oxidative pathway and increase NADPH production
139
what is the significance of carbohydrates attached to glycoproteins?
involved in cell-cell recognition and attachment
140
why is mannose-P important?
it's recognized by phosphomannose which helps the cell direct the mannose-P to lysosomes
141
what are the symptoms of I-cell disease?
skeletal abnormalities, coarse facial features (children will look like an adult), delayed development of motor skills
children will be normal at birth but overtime they will start to develop symptoms
142
what are glycolipids?
derivatives of lipid sphingosine, contain CERAMIDE, produced in GOLGI APPARATUS
143
differentiate cerebrosides from gangliosides
cerebrosides contain only ONE sugar residue (galactose aka galactocerebroside) or glucose (glucocerebroside)
gangliosides contain MANY sugar residues and will always have at least one NANA residue
144
explain the importance of glycosyltransferases in blood groups
Type A - has glycosyltransferases that transfer a GalNAc
Type B - has glycosyltransferases that transfer a Gal
Type O - do NOT have glycosyltransferases so they only contain H substance
145
what are the 5 types of lysosomal storage diseases?
Pompe (alpha 1,4 glucosidase deficiency)
I-cell disease (phosphoryltransferase deficiency)
Tay-sachs (Hexosaminidase A deficiency)
Niemann-Pick (sphingomyelinase deficiency)
Gaucher (beta-glucosidase deficiency) = MOST COMMON
146
why is ApoE important?
it allows the chylomicron remnants to bind to the receptors on the liver and enter via receptor-mediated endocytosis
once the chylomicron remnants enter the liver, the TG, cholesterol, phospholipids, and fat-soluble vitamins can be further processed
if ApoE is deficient can lead to elevated TG levels in serum because it can't be processed in the liver
147
explain adipose LPL
has a higher Km (because it is a storage, you won't need to use it for energy as much as the other cells/organs do, you only store it when you have too much) than LPL associated with other tissues
synthesis and secretion is upregulated by INSULIN, most active in fed state
148
describe digestion of TG
begins in the mouth and stomach with lingual and gastric lipase
chyme moves into small intestine, it is emulsified with bile salts secreted by the gallbladder
in small intestine, pancreatic lipase and colipase hydrolyzes TAGs to free fatty acids and 2- MG --> taken up by intestinal epithelial cells and RE-ESTERIFIED and incorporated into chylomicrons
149
explain bile salts
derivatives of cholesterol made in liver and secreted into the DUODENUM
is AMPHIPATHIC (composed of hydrophilic outer layer (lysophospholipid) and hydrophobic inner core (cholesterol, FA, 2-MG)
150
explain recycling of bile salts
95% is resorbed in the ileum, taken up by the LIVER, rest is eliminated in feces
elimination of bile salts in stool is body's PRIMARY MECHANISM of removing cholesterol
some drugs used to treat HYPERCHOLESTEREMIA decrease resorption of bile salts (derived from cholesterol) in ileum
151
explain resynthesis of TAGS
free FAs, MAGs, cholesterol, lysophosphoplipids, and other digested lipids DIFFUSE into INTESTINAL EPITHELIAL CELLS (SC and MC FAs diffuse into circualtion) while remaining lipids are RE-ESTERIFIED and incorporated into chylomicrons
before esterification, LC and VLC FAs must be activated by CoA (2-MG-->DAG-->TAG)
152
what happens when MTP is deficient?
unable to generate chylomicrons and VLDL
153
when is alpha-lactalbumin expressed?
after childbirth in response to PROLACTIN
154
what happens to galactosyltransferase in the absence of alpha-lactalbumin?
it has a VERY LOW AFFINITY for glucose, transfers galactosyl from UDP-galactose to glycoproteins
