Tissue specific metabolism Flashcards
Hepatocytes metabolize what nutrients
CHO, AA, lipids
What are the functions of liver
Provides energy precursors to all tissues
Maintains balance between nutrient supply and precursor demand
Nutrient supply and precursor requirement varies
Nutrient: varies with diet and feeding
Precursors: varies with level of activity and health
enzymes in liver are sensitive to
Various hormones
Liver has a flexibility in
Enzymatic machinery
White Adipose tissue (WAT) are situated
Under skin, around major blood vessels and abdomen
What are adipocytes
One lipid droplet
Energy source for WAT
glucose
WAt can do what
Capable of FAs synthesis from glucose- insulin sensitive
WAT is the major storage of
TAG
How do get TAG from WAT
Hydrolysis to NEFA (epinephrine sensitive)
where BAT are
Under skin (chest and back)
Who has BAT
Only in children ,not adults, but new studies have shown can be found in adult also
Why BAT are brown
Many mitochondria and high blood supply
How many droplets BAT has
Many
What is the energy source for BAT
Fatty acid through beta-oxidation
Major role of BAt
Non-shivering thermogenesis- thermogenin (UPC1)-> maintain body temperature
How can we get BAT
Preadipocytes can differentiate into BAT in adults during chronic cold exposure
Muscles can use what fuel
Resting state: FA from adipose and ketone bodies from liver
Moderate: Blood glucose(aerobic glycolysis) in addition to FA and ketone bodies
Vigorous: stored glycogen gives glucose
Each glycogen origin glucose give how many ATPs
3
The result of anaerobic glucose metabolism is
Lactic acid
What is the additional pathway in muscles for ATP
Phosphocreatine
How can we synthesize creatine
Dietary
OR
De novo (glycine, arginine, methionine)
What hormone helps in using glucose from blood and glycogen
Epinephrine
Muscles can maintain temperature through
Vigorous contraction->shivering thermogenesis
What happens in muscles during recovery through activity
Lactate is converted to glucose in liver (kori cycle)
Creatine ->phosphocreatine
What metabolism is carried by cardiac muscles
Aerobic
Mainly FAs, but can also use ketone bodies and glucose
What cellular structure is abundant in cardiac muscles
Mitochondria
Comparing to skeletal muscles, cardiac muscles have less
Stored glycogen
Cardiac muscles are sensitive to
O2 deprivation
Neurons are highly dependent on
Glucose energy
How many grams of glucose neurons use every day
130 grams
Atp is used fr what in neuron
To maintain membrane potential (Na+ K+ATPase)
Apart form glucose, neurons can use
Beta-hydroxybutyrate
What are astrocytes and what so they use
star-shaped glial cells in the brain and spinal cord.
They use FA
Does brain store glycogen?
No
What metabolism is performed by FAs
Aerobic
What fuel is used by neurons during fasting/starvation
Ketone bodies (from FA) Glucose (from muscle protein)
What happens immediately after meal
Glucose level rise
Glycolysis and glucogenesis rise ( insulin levels rise)
What happens 2 hours post-prandial
Glucose begins to drop
Liver glycogen releases glucose (glucagon)
What happens 4 hours post-prandial
More glucagon
More TAG hydrolysis, FA become major fuel
Metabolism in prolonged fasting
Glucose is at the minimal levels
FAs are depleting fast
Non-essential AAs are deaminoated and the carbon backbone can enter TCA cycle and lead to oxaloacetate-> glucoenogenesis->glucose dependent cells
beta-oxidation pathway->accumulation of acetyl-CoA->ketogenic pathway, because oxaloacetate is depleted-> no TCA
Does fat accumulation lead to more energy source during starvation?
Ketone bodies accumulation-> toxic-> fat people will not starve longer
T1DM are due to and develops when
Due to autoimmune destruction of Beta-cells->insufficient production of insulin
Develops early in life
T2DM are due to and develops when
Usually develops in late adulthood
Cells do not respond appropriately to insulin
Typically INSR signaling is affected ->IRS proteins are dephosphorylated
GLUT4 is trapped inside of the cells in cytoplasm
What is the purpose of INSR signalling
Usually regulate gene expression that is needed for inflammation, stimulated of cytokines
Cytokines influence what mechanism
JAK-STAT mechanism
JAK-protein
STAT-TF
This mechanism influence SOC 1 and 3 and they help to regulate the pathway of inflammatory cytokines
Inflammatory cytokines are coming from
Adipose tissue
How Inflammatory cytokines pathway can influence RTK
SOC 1 and 3 can inhibit phosphorylation of IRS by insulin receptor-> insulin resistance-> no GLUT 4 brought
In both types of diabetes what are the consequences to metabolism
Blood glucose is high
Increased osmolarity-excessive urination and thirst
Proteins get glycosylated-> inhibits protein activity
In T1DM, fat breakdown accelerated, because there is not enough glucose for energy-> high ketone bodies. What is the effect
Raise in blood H+, leads to ketoacidosis
Bicarbonate buffering system (RBCs) is activated, leads to altered breathing pattern-> accelerated breathing
Acetone breathe, because of break down of acetoacetate to acetone
Untreated T1DM leads to
Dramatic weight loss
Adipose tissue is ___ organ
Endocrine
Adipose tissue release
Adipokines- one of the main leptin hormones, another one is adiponectin
Adipokines: role
Carry info about fuel stores to brain
The difference between anorexigenic neurons and orexigenic neurons
Anorexigenic- less eating, more burning
Orexigenic neurons- less energy expenditure, more eating
What are stimulators and inhibitors for anorexigenic protons
Leptin
No inhibitor
What are stimulators and inhibitors for orexigenic protons
Inhibitor:leptin, insulin, hormone from gut (satiety signals)
Stimulator:ghrelin(stomach) hunger signals
Leptin ___ appetite
Reduces
What were the mice that had ob/ob-obesity gene
Ate continually, obese, elevated cortisol, shivered, infertile, insulin resistance, died early
What happened to mice with leptin injected into obese mice
The mice lost weight, temperature returned to normal
Did leptin injection helped obese people?
No, they have higher leptin levels ( not deficiency)-> leptin resistance
Leptin resistance ultimately leads to
Diabetes
What does db gene encodes
Leptin receptor in brain, expressed mostly in hypothalamus ( functions in food intake and fertility)
There are ghrelin receptors are in
Brain, heart, adipose tissue
Ghrelin works through what mechanism
GPCR to increase sensation of hunger
PYY is
An appetite-suppressing hormone
Why PYY peptide is called like that
36 AA with two Tyr (Y) residues in the end
PYY secreted from
The small intestine and colon
PYY results in
Reduced hunger
Inhibits release of NPY - stops oroxigenic neurons
Obese and lean people have
Microbiota
How microbiota can affect adipose tissue
Most bacterial products are short chain FAs
Propionate acts through GPCR 43 and 41-> stimulates adipocyte differentiation and inhibits lipolysis
Lipid burden hypothesis link between Obesity and T2DM
Obesity leads to diabetes
As a person starts accumulating fat->MCP-1 is secreted acts as a trigger for macrophages-> accumulation of macrophages in adipose tissue->proinflammatory hormones (TNF)-> increased release of FAs-> accumulation of FAs in circulation->ectopic lipid interference with GLUT4->inhibit the signaling of bringing GLUT 4 to the surface
