Professional Documents
Culture Documents
Control of balance between substrate need and substrate availability is known as?
Three ways that intertissue integration for metabolic homeostasis is achieved?
Determines whether skeletal muscle will use fatty acids or glucose as fuel
Two major hormones that regulate fuel storage and mobilization?
Major anabolic hormone of the body?
Promotes storage of fuels and utilization of fuels for growth?
Major hormone of fuel mobilization?
Minimum amount of glucose required a day for an adult?
Cutoff for absolute minimum amount of blood glucose before hypoglycemic episodes?
Overall process of glucose flux through the BBB -> into interstital -> neuronal cells is ____
at low blood glucose levels?
Effects that would occur if even a day's worth of glucose, AA, and FA's could not enter
cells normally?
Metabolic Homeostasis
1. Concentration of nutrients affects rate at with used/stored
2. Hormones carry messages about supply and demand
3. CNS uses neuronal signals to control tissue metabolism
Concentration of FA
Insulin and Glucagon
Insulin
Insulin
Glucagon
190 g (150 for brain, 40 for other tissues)
60 mg/dL
Slow
1. Glucose and AA would be in hyperosmolar concentrations in the blood -> severe
neurological problems
2. Glucose and AA [] could rise above renal threshold, can't completely resorb metabolites
-> spill into urine
3. Nonenzymatic Glycosylation of proteins -> alter tissue function
4. TAGs and VLDL would rise -> increased risk of athlerosclerotic plaque build up
Insulin
Degradation
Promotes Glucose -> FA and FA -> TAGs (inhibits TAGs -> FA)
Promotes AA -> Proteins and Glucose -> Glycogen and CO2
Promotes Glucose converstion to Glycogen and FA; also promotes AA -> Proteins (inhibits
catabolism and gluconeogenesis)
Promotes TAGs -> FA (for fuel) and subsequent FA release from Tissues
No Effect
Promotes Glycogen -> Glucose, AA -> Glucose (Gluconeogenesis), and Glucose release from
Liver (inhibits storage of glucose)
Insulin Spike and Glucagon Fall
Skeletal muscle
Approx. 30-45 minutes after a meal
oppose the actions of insulin by mobilizing fats
Neuronal signals
direct response to changing levels of fuels in the blood
Stimulates glucose production from glycogen
Stimulates FA release from Adipose Tissue
Catabolism of Muscle protein for AA release
Stimulates FA release from Adipose Tissue
Stimulates usage of AA for gluconeogenesis
Epinephrine
Cortisol
ACTH (from Anterior Pituitary)
ANS
Low Blood Glucose and ANS (minor role in the release of glucagon)
Glucose is plentiful and available for use as fuel or storage
A tumor that produces excessive insulin
Reduced blood glucose levels due to uptake into tissues
Hepatic Portal Vein (via the pancreatic veins)
Two
3, two interchain and 1 intrachain (A-chain)
rER
Cysteine residues
In the storage vesicles secreted by the Golgi
Zinc
GLUT2
G6P
metabolized
Increased ATP
It is inhibited
Membrane Depolarization
Ca2+ channel
Fusion of the insulin-containing transport vesicles with the PM
Synthesis of new insulin
Less than the amount released during a high carb meal
GLP-1 and GIP (released after ingestion of food)
In the rER
Lumen of the ER
Liver and Kidneys
3-5 minutes
Release of glucagon
-cells (they are downstream from the -cells)
Amino Acids
Catecholamines
insulin levels drop
Insulin would rise (not as much as after carbo meal) and glucagon would show great
increase (well above fasting)
Antibody mediated destruction of -cells
genetic defect in the gene that codes for MHC II (self recognition)
glucokinase mutation that results in an ezyme with a elevated Km (lower affinity for glucose
- less efficient)
higher than normal
Hyperglycemic State
Within the first 3 months of life
KCNJ11 gene mutation
Activating mutation for the K+ channel
keeps it open, and less susceptable to the ATP inhibition -> no Ca2+ channel activation ->
no insulin secretion
Make it difficult to close the K+ channel -> display neonatal diabetes
C-peptide, it is not cleared from the blood as rapidly as insulin
Yes, because exogenous insulin does not contain C-peptide
Decreased, or barely existant
Normal or elevated, but it is not enough to combat the hyperglycemia
Insulin binds to subunit -> spans the membrane -> TK phophorylates tyrosine residues
on (autoP) -> IRS1 phosphorylated ->
IRS-1 binds to SH2 domains
1. Reverse glucagon stim. Phosphorylation
2. PO4 cascade that phosphorylates many enzymes
3. Induces represses/induces synthesis of specific enzymes
4. Insulin acts as a GF and has a general stimulatory effect on protein synth
Insulin causes __________ of of the synthesis of enzymes that are induced by glucagon
Key enzyme in the gluconeogenic pathway?
Phosphoenolpyruvate Carboxykinase is increased by what?
Phosphoenolpyruvate Carboxykinase is decreased by what?
Antagonism is exerted through
Biochemistry - Chapter 43
Somatostatin inhibits the release of what two hormones?
GH
Insulin
Glucagon (indirectly)
D-Cells
28 (SS-28)
70-75%
7-10 times
No
Glucose, Argininine, Leucine, Glucagon, VIP, CCK
G coupled proteins
5
4
Production of cAMP and PKA
Suppression of secretion of GH and TSH
Gastrin
Pancreatic enzyme secretion
Nutrient Absorption
Somatomedins
GH binding to plasma membrane receptors
17
Human Prolactin and Human Chorionic Somatomammotropin (hCS)
Hepatocytes
An early increase in 8-10 proteins, among which are IFG-I, 2-macroglobulin, and serine
protease inhibitors
Ornithine Decarboxylase
Adipose
Muscle
Arcuate Nucleus
in the first 29 AA of the N-terminal portion
GH release
IGF-1 (produced in the liver, in response to GH secretion)
Decreases GH secretion
Increases GH secretion
Increases GH secretion
FA release can decrease GH secretion due to increased AA or hypoglycemia. However,
Prolonged fasting utilizes FA increases GH.
GH
GH
Free FA and Glycerol
Liver
Insulin
The muscle
Glucose (and glucose uptake)
Increases the rate of AA uptake by muscle -> substrate for protein synthesis
Has a positive effect on nitrogen balance
Enhances it, thus enhancing ketogenesis
Gluconeogenesis
When GCs are elevated, what happens to glucose uptake by the cells of many tissues?
Why does this occur?
If the levels of PEPCK is increased, what does that signal the liver to do?
Effect of GCs on muscles?
Primary neoplasm of the adrenal cortex will cause what to happen the levels of ACTH and
cortisol, respectively?
Where is the protein thyroglobulin synthesized?
Where is the protein thyroglobulin secreted into?
Iodine trapping mechanism is poorly defined but may involve an?
With RIA, the higher the amount of unlabeled hormone in the sample, the less what?
Thyiod peroxidase
T3
t4 (7 days)
It is free and unbound, therefore it can diffuse across target cell membranes to interact with
intracellular receptors
Liver, kidney, muscle and other tissues via deiodination -> produces compounds with no bio
activity
lysosomal proteases
cAMP, it also increases the level of inositol trisphosphate and diacylglycerol -> cytosolic
Ca2+ w/in the thyroid cell
Goiter, in an attempt to produce more thyroid hormone.
Liver: increase glycolysis, cholesterol synthesis, and conversion of cholesterol into bile salts
Adipose: amplifies the effect of E on fat cells but also increases the availability of glucose to
fat cells
Muscle: increases glucose uptake by muscle cells and stimulates protein synthesis - growth
of muscle
Pancreas: increases sensitivity of -cells to stimuli that normally promote insulin secretion
greater -cell response seen after an oral glucose load, as opposed to one that is
adminstered IV
GLP-1 and GIP
GLP-1
GIP
Sitagliptin
Twice
Vagus (increased) and sympathetic fibers (decreased)
Both adrenergic and cholinergic limbs of the ANS
CB1
The "reward" potential of addictive drugs
Mesolimbic-dopaminergic system
A high fat diet
Adipocytes
1. Nutritional Factors
2. Level of activity
3. Consciousness
4. Stress
5. High protein meal
6. Low level of FA or glucose in the blood
7. Vigorous exercise
8. Sleep
9. Stress
10. Levadopa
11. Clonidine
12. Estrogens
1. Patient must not have eaten for 6-8 hours
2. Patient must not have done any vigorous exercise for at least 4 hours
3. Patient must remain fully awake for the duration of the test
4. Patient must not have taken any drugs that increase GH for at least 1 week
The less radiolabeled hormone is bound
Biochemistry - Chapter 48
Most abundant type of cell in the nervous system?
Glial consists of?
Astrocytes and Oligodendrocytes are found in the
Shwann Cells are found in the?
These cells provide support and synthesize what?
The myelin sheath surrounds the ?
Act as immune cells in the NS, destroying and ingesting foreign organisms?
Interface between brain parenchyma and CSF are the?
Where are they found?
These cells use their ______ to move the CSF, which bathes the cells of the CNS
Neurons are terminallly ______ and have very little capability for division
Astrocytes are found in the CNS and are ____ shaped?
Regulate the EC environment: taking up, processing, and metabolizing nutrients and
waste products?
Provide the myelin sheath that surrounds the axon?
Oligodendrocytes can form myelin sheaths around multiple neurons by sending out what?
If oligodendrocyte is damaged it will not _______
Supporting cells of PNS that can myelinate only one axon?
Damaged PNS axons can do what with their appropriate targets post-damage?
Blood Brain Barrier:
Glial
Astrocytes and Oligodendrocytes
CNS
PNS
Myelin
Axon
Microglial cells
Ependymal cells
Lining the cavities of the brain and spinal cord
Cilia
Differentiated
Star
Astrocytes
Oligodendrocytes
Processes that bind to axons on target neurons
replicate
Schwann Cells
Reconnect
1. Tight Junctions at endothelial cells - no polar molecules
2. Narrow intercellular spaces
3. Lack of pinocytosis
4. Continuous Basement Membrane
5. Astrocyte Extension
1. Enzymatically
2. P-glycoproteins = actively pump hydrophobic molecules back into the blood from the
endo cell
GLUT-1
GLUT-3
GLUT-1
Experience hypo-glycemic symptoms
Ketone Bodies
Up-regulated
GLUT1 deficiency
hypoglycorrhachia
CSF Glucose to Blood Glucose Ratio of less than .4
High Fat, Low Carb diet -> force the body to use Ketone Bodies as fuel
Seizures, developmental delay, and complex motor disorder
BBB transporter
They are synthesized there
Proved that competitive antagonism via other AA can lower levels of phenylalanine in the
brain, and improve symptoms
1. Small Nitrogen-containing NTs
2. Neuropeptides
The specific neurotransmitter that they use
Neuropeptides
Endorphins -> bind to opioid receptors and block pain signals
TSH and GH
Tyrosine Hydroxylase
End product inhibition
CREB
Dopamine Decarboxylase
Tyramine
NE receptors
MAO-A
MAOIs
Urine
Phenoxybenzamine
Tryptophan Hydroxylase
PLP + Dopa Decarboxylase
MAO
Tryptophan
Pineal Gland
Light/Dark Cycle (increases in the dark)
Clorgyline
Deprenyl
Dopamine
Deprenyl
Reversible, Moclobemide
No Cheese Effect
Mast Cells
In the thalamus, hypothalamus, dura mater, leptomeninges and choroid process
Histidine Decarboxylase + PLP
PreS and PostS receptors
Recycled
Astrocytes
Methylation via histamine methyltransferase
Oxidation via MAO-B
Increased Appetite and Decreased Mood (Depression)
Redux
MAOIs, Tricyclics, and SSRIs
Vasodilation and Increased Permeability of Blood Vessels
Airways to constrict in an attempt to reduce the intake of allergic material
Excitatory
ChAT (in the preS terminal)
Low and High
Phosphatidylcholine and Sphingomyelin
Add 3 methyl from SAM to ethanolamine end of phosphatidyethanolamine ->
phosphatidylcholine -> hydrolyzed to choline
B12 and folate
Glucose -> Pyruvate and decarboxylation of Pyruvate -> Acetyl CoA
ONLY in Mitochondria
AChE
AChE
Glutamate
1. Glutamate Dehydrogenase (reduces -ketoglutarate -> glutamate) - incorporates free
ammonia into backbone
2. Transamination reactions (AA -> -keto -> glutamate)
Glutaminase
Glial Cells
GABA
Decarboxylation of glutamate
Glutamic Acid Decarboxylase
GABA Shunt (converse GABA and Glutamate)
Glial
GABA shunt in glial -> glutamate -> glutamine -> transported out of glial -> neurons ->
converted back to glutamate
Glutamine
GAD
Lecithin supplementation
ACH
Phosphatidycholine
Increased
Deprives the brain of a source of acetyl CoA
Tiagabine
Aspartate
Glycine
Serine Hydroxymethyltransferase (requires Folic Acid)
The intermediate 3-phosphglycerate in the glycolytic cycle
High affinity uptake transporter
Vitamin B12
NO
Arginine
NO synthase
1. Macrophage Form - overproduction of NO -> cytotoxic actions on paracites/tumor cells
2. Nervous Tissue Form - Physiologic action of NO -> vasodilation and neural transmission
guanylate cyclase -> cGMP
cAMP -> kinases -> relaxation of smooth muscle and dilation of vessels
NO
Retrograde messenger
20%
2 molecules
32 molecules
Hypoglycemia
TCA intermediates and glutamate - these are quickly depleted
Glucose level below 1 mM
EEG become isoelectric -> neuronal cell death ensues