Integration of Metabolism Flashcards
Possible fates of G6P?
1.Stored as glycogen
2.converted via glycolysis anf PDH to acetyl COA –>ATP
2 . precursor for FA and cholesterol synthesis
3. enter PPP to make NADPH and ribose 5 phosphate
fates of Amino acids
(1) protein synthesis-liver and plasma proteins
(2) enter bloodstream to be used by other tissues to make proteins
(3) used as precursors for biosynthesis of nucleotides, hormones, other compounds
(4) yield products that enter TCA cycle; ammonia converted to urea and excreted
(5) Pyruvate converted to glucose and glycogen
(6) converted to acetyl-CoA, then oxidized via (7) the TCA cycle and (8) OXPHOS to produce ATP
(9) used to make lipids for storage
(10) TCA cycle intermediates make glucose
(11) muscle proteins converted to alanine, which is can be used to make glucose in liver via the glucose-alanine cycle
F.A Metabolism in Liver fates ?
converted to liver lipids;
(2) oxidized to give acetyl-CoA and NADH;
(3) acetyl-CoA further oxidized via TCA cycle and (4) used to make ATP via OXPHOS;
(5) excess acetyl-CoA is converted to ketone bodies (fuel for heart, and for brain during prolonged fasting)
(6) some acetyl-CoA used for synthesis of cholesterol;
(7) fatty acids can be converted to the TAGs and the phospholipids of plasma lipoproteins;
(8) and some is bound to serum albumin and carried to heart and skeletal muscle for use as fuel
Metabolism in Adipose Tissue
in notes
__+__=energy consumed
energy expended + energy stored
Short-term biochemical signals (all are peptides)
Originate from ?
GI tract, beta cells of pancreas, and fat cells
Short-term biochemical signals target ?
arcuate nucleus of the hypothalamus
What are Two signals relay feelings of satiety?
- chloesystokin- secreted by the SI
2. glucagon like peptide 1
Ghrelin?
Ghrelin: secreted by stomach, stimulates appetite
when leptin binds to its receptor it __?
Binding to its receptor increases sensitivity of muscle and liver to insulin, stimulates b-oxidation of FAs, and decreases TAG synthesis
orexigenic
appetite stimulating
neurons in the arcuate nucleus inhibit __
Neurons in arcuate nucleus: inhibits production of appetite-stimulating (orexigenic) peptides Neuropeptide Y (NPY) and agouti-related peptide (AgRP)
Insulin inhibits ______, thereby inhibiting food consumption.
NPY/AgRP-producing neurons,
describe the process of the insulin signaling
in notes
Most obese people have high blood levels of leptin.
But they have leptin resistance. Why?
Because of overactivity of Suppressors of Cytokine Signaling (SOCS) proteins
Disrupt interactions among components of insulin (& leptin?) signaling pathway, inhibiting it
1921: __ and __ discovered insulin is produced in the pancreas (dogs).
Frederick Banting and medical student Charles H. Best
type 1 diabetes is insulin dependent caused by?
destruction of pancreatic Beta cells
Type II (NIDDM) is characterized by?
insulin resistance
dyslipidemia?
—called metabolic syndrome, a precursor to diabetes
in the pricess on secteting insulin , high ATP/ADP ratio will cause ?
K+ channels to close, Ca2 channels to open, influx of Ca2+ and release of insulin
How does insulin resistance cause pancreatic failure?
Normally, ER in b-cells processes proinsulin to mature insulin
As insulin resistance develops, ER ramps up effort to process insulin, but becomes overwhelmed,
ER is stresssed and caused B cell apoptosis
in Type 1 Diabetes Patient is in a biochemical fasting mode despite high blood concentration of glucose causing ?
cells to be starved and Liver is “stuck” in ketogenic and gluconeogenic mode
High glucagon/insulin ratio
causes
inhibition of glycolysis
promotes glycogen breakdown in liver—excessive amount of glucose produced by and released from liver
Result: glucosuria, polydypsia
Uncontrolled breakdown of lipids and proteins yields high levels of ___?
ketone bodies (ketogenic state)
in the fed state Glucose and amino acids transported from __ into blood
intesine
in the fed state lipids are packaged into __ and tranported into the blood via ___ system
chylomicrons
lymphatic
the fed state stimulates ?
storage of fuels and synthesis of proteins
Stimulates glycogen synthesis in muscle and liver; suppresses gluconeogenesis; stimulates glycolysis in liver, which, in turn, increases fatty acid synthesis
How is excess blood glucose after a meal removed?
Glucokinase: acts to trap large quantities of glucose in the liver as Glu6P
Rise of Glu6P, together with insulin action, leads to the buildup of glycogen
entry of glucose into muscle and adipose tissue
stage two of the starved fed cycle
early fasting or postabsorbative
Stimulates glycogen breakdown and inhibits glycogen synthesis
inhibit FA synthesis; stimulate gluconeogenesis
in the early fasting stage Entry of glucose into muscle and adipose tissues __ as insulin level declines
decreases
What is result of liver glycogen depletion?
Gluconeogenesis from lactate and alanine continues, but this just replaces glucose used
stage 3 of starved fed state?
refed stage
Liver remains in gluconeogenic mode, but glucose used to replenish glycogen; and FA synthesis
what is Priority #1 during fasting?
Provide sufficient glucose for brain and other tissues (RBCs) that are dependent on it
what is Priority #2 during fasting?
to preserve protein by shifting fuel source to fatty acids and ketone bodies
Metabolic Changes during Day #1 of Starvation?
liver uses mainly fatty acids for fuel
In Metabolic Changes during Day #1 of Starvation what causes inhibition of glycolysis?
b-oxidation of fatty acids produces acetyl-CoA, which stimulates phosphorylation and inhibition of PDH
Increase of Acetyl CoA and citrate
by day 3 of starvation __ is secreted by liver
ketone bodies
3 stages of liver damage
) Fatty liver stage
(2) alcoholic hepatitis: groups of cells die and inflammation results
(3) cirrhosis of the liver:
: ethanol consumption leads to accumulation of?
NADH
microsomal ethanol-oxidizing system (MEOS)?
Cytochrome P-450-dependent; generates acetaldehyde, then acetate; also NAPD+
What causes oxidative stress in MEOS
P-450 enzyme uses O2 and consumes the NADPH needed to form GSH; free radicals are produced and not adequately removed,
Excess alcohol disrupts vitamin _ metabolism
A
Other disruptions due to alcoholic malnutrition?
Wernicke-Korsakoff syndrome due to thiamine insufficiency, and (2) alcoholic scurvy due to vitamin C insufficiency
leptin ?
Binding to its receptor increases sensitivity of muscle and liver to insulin, stimulates b-oxidation of FAs, and decreases TAG synthesis
