L32 - Metabolism 2 Flashcards
What are proteins used for?
cell signaling receptors, signaling molecules, enzymes & intracellular trafficking components, extracellular matrix scaffolds, ion pumps, ion channels, oxygen and CO2 transporters (hemoglobin) + growth and repair
What are amino acids?
the building blocks of protein
What are proteins broken down to?
amino acids that can be used as metabolic substrates, less important than carbohydrate and fat
What are essential AAs?
cannot be made by the body, must come from food
leucine, isoleucine, valine, phenylalanine, threonine, methionine, lysine, tryptophan, histidine, arginine
What are non-essential AAs?
alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, tyrosine
Each amino acid has its own specific…
metabolism
How are proteins broken down and how are their components transported?
enzymes in the stomach / SI break down proteins into AAs, which are released into the bloodstream -> AA transporters are membrane-bound proteins that mediate transfer of AAs into and out of cells or cellular organelles
How are amino acids concentrated in the cell?
active transport mechanisms are used
What are the diverse range of functional roles carried out by AATs?
neurotransmission, acid-base balance, intracellular energy metabolism, and anabolic and catabolic reactions
What are amino acids mostly used for?
protein anabolism (i.e. new protein production) and a source of energy, especially in times of starvation
Why are amino acids useful in times of starvation?
because the processing of AAs results in the creation of metabolic intermediates, including pyruvate, acetyl CoA, oxaloacetate and α-ketoglutarate, amino acids can serve as a source of energy production through the TCA cycle
Is amino acid contribution to ATP synthesis generally high or low?
low (except starvation)
How are amino acids used to produce glucose?
pyruvate is transaminated with ammonia, derived from muscle protein catabolism, to produce alanine -> alanine is released from muscle and taken up by liver to produce glucose -> toxic ammonia is converted to urea in the liver
What are hormones?
generally proteins secreted by cells into the blood for transport to a distant target, secreted by most tissues, exert their functions at very low concentrations, degraded rapidly in blood so that their effects are of limited duration
How do hormones work?
bind to receptors on the surface of target cells
generally activate second messenger signalling pathways (i.e. signal transduction), which can induce a cellular response (e.g. activate enzymes)
What is the exocrine function of the pancreas?
functions as an exocrine gland secreting pancreatic juice into the duodenum (digestion, 99% of pancreas)
What is the endocrine function of the pancreas?
within pancreatic islets (1% of pancreas, endocrine function):
β-cells (secrete insulin)
⍺-cells (secrete glucagon)
What is insulin secretion increased by?
high blood glucose levels, amino acids, incretin hormones, feeding-induced parasympathetic neural activity to the pancreas
Does the digestion and absorption of food containing both carbohydrates and proteins provide strong stimulation for insulin release?
yes
What are incretin hormones?
include GIP and GLP-1, which are released by enteroendocrine cells of the SI in response to the presence of glucose in the GI tract
What is an important feature of insulin signalling?
translocation of GLUT4 from the cytosol to the plasma membrane which allows for an increase in glucose uptake
What is glucagon secretion increased by?
low blood glucose levels + increased activity of the sympathetic division of the autonomic nervous system, as occurs during exercise or prolonged fasting
What does glucagon activate?
Gs receptors, which stimulate AC to produce cAMP that activates PKA
What is the role of PKA?
phosphorylates enzymes that control metabolism, leading to their activation (e.g. glycogen phosphorylase) or promote gluconeogenesis (via CREB)
What is the primary target tissue of glucagon and insulin?
the liver; the major effect is increased or decreased release of glucose into the bloodstream, respectively
Which factors is substrate metabolism controlled by?
many factors including the prevailing nutrient supply, hormones and the activity level of the individual
What is the fed state?
ingested nutrients are entering the bloodstream, and glucose is readily available for ATP production
FAs are mostly available as triglycerides in chylomicrons (from GI tract)
How much glucose is used for anabolic metabolism?
half of glucose
What is the fasted state?
absorption of nutrients from the GI tract is complete, and energy needs must be met by fuels already in the body (stored glycogen, triglycerides and proteins)
How long does it take for complete absorption of a meal?
typical meal requires about 4 h for complete absorption; given three meals a day, the absorptive state exists for about 12 hours each day
How does whole-body substrate utilisation change between the fed and fasted state?
the RER tells us the proportion of fuel which is coming from glucose and FAs
RER of 0.7 = burning 100% fat, RER of 1.0 = burning 100% carbohydrate
What happens in most tissues during the fed state?
~50% of glucose absorbed and oxidised by tissues
What happens in the liver during the fed state?
glucose is stored as glycogen and some glucose can be converted to FAs
AAs can be used to synthesise fatty acid and glucose
AAs are used for protein synthesis
What is lipogenesis?
converts excess dietary carbohydrates, proteins, and fats into triglycerides
stimulated by insulin and occurs mostly in liver
Which pathways convert glucose into FAs?
glucose -> G-3-P -> glycerol -> triglyceride
glucose -> G-3-P -> acetyl CoA -> FAs
Which pathways converts AAs into FAs?
AAs -> acetyl CoA -> FAs
What happens in the muscle during the fed state?
glucose is stored as glycogen and some amino acids are used for protein synthesis
What happens in the adipose tissue during the fed state?
TG contained within lipoproteins can be broken down and the released FAs stored as TG (minimal), glucose -> TG
most dietary lipids, most notably TG within chylomicrons (GI tract), are transported into adipose tissue and stored as TG
lipolysis is inhibited
Which metabolic changes does insulin regulate?
facilitated uptake of glucose into cells, active transport of amino acids into cells and protein synthesis, glycogen synthesis (glycogenesis), lipogenesis in liver and adipose tissue, inhibition of lipolysis
What occurs in the liver during the fasted state?
glycogenolysis ↑, gluconeogenesis ↑, ↑ delivery of substrates including AAs and glycerol -> maintenance of hepatic glucose production to sustain blood glucose levels
What is ketogenesis?
hepatocytes convert FAs to ketone bodies, which can be used by the heart, kidneys, brain and other tissues for ATP production
this occurs in the liver during the fasted state
What is gluconeogenesis?
production of glucose from AAs, glycerol and lactate, process is essential to maintain blood glucose levels in fasted state, stimulated by glucagon, inhibited by insulin
What happens in the adipose tissue during the fasted state?
adipose tissue lipolysis is increased, providing FAs for oxidation / ATP generation and glycerol for gluconeogenesis
What happens in the skeletal muscle during the fasted state?
modest breakdown of proteins supplies amino acids to the liver for gluconeogenesis
FA oxidation increases considerably
glycogenolysis occurs for ATP production
What is the role of glucagon in the fasted state?
regulates liver glycogenolysis and gluconeogenesis
What is the role of adrenaline in the fasted state?
regulates liver and muscle glycogenolysis and adipose tissue lipolysis
