Last Exam 1 Flashcards
Reminder: walk me through glycolysis and the TCA cycle…
How much NADH, FADH2, and (net) ATP is generated during glycolysis, conversion of pyruvate to acetyl CoA, and during the krebs cycle?
And total net ATP yield (after electron carriers also converted)?
Glycolysis (2 ATP, 2 NADH), conversion (2 NADH), Krebs (2 ATP, 6 NADH, 2 FADH2)
36 ATP
What are the key features in the regulation of metabolic pathways? [3]
What is phosphofructokinase? What stimulates it? What inhibits it?
What is the name of the enzyme that acts as a critical sensor of cellular energy? How many subunits does it have? What does each one do?
Key enzyme in glycolysis (adds phosphate to fructose phosphate in order to help split it apart) - stimulated by AMP, inhibited by ATP
AMP Kinase (three subunits - alpha [catalysis], beta [carbohydrate binding], gamma [binds AMP])
What regulates AMPK enzyme?
What does the activated enzyme do?
Ratio of AMP:ATP
Adds phosphate group to ADP to restore ATP
When AMPK is activated, what is up/downregulated? What is the main purpose of all of these changes?
Maximizing the creation of ATP
How much of blood going to the liver comes from the heart (via hepatic artery)? How much comes from the portal vein?
Which vein does blood leave the liver in?
20-30%, 70-80%
Hepatic vein
What is the plasma level of glucose?
How many glucose transporters are there? Are they active transporters? What areas of the body is each one found in? What is the Km of each one (and why might this be important)? Which one(s) are insulin sensitive?
5mM
It is facilitated, not active - requires a gradient. Different tissues have different needs (EG: GLUT1/3 (serving brain) have low Km, so will be taking in glucose even at low serum glucose levels)
Why does GLUT2 (liver) have a high Km?
What is the name of the enzyme that phosphorylates glucose at this location? How is it different to the similar enzyme in muscle?
Low affinity - ensures it only works when glucose is high (glucose sensing)
Glucokinase - higher Km than hexokinase (so only performs function when glucose levels are high), higher Vmax (so doesn’t get overwhelmed), and isn’t inhibited by G6P
Why is glucose phosphorylated when it enters cells?
What enzyme converts G6P to glycogen?
What else could happen to G6P?
To stop it leaving
Glycogen synthase
It can be converted back to glucose and released back into the circulation, or it can be metabolized by glycolysis to pyruvate, or it can go down the pentose phosphate pathway (creation of NADPH, nucleic acid, nucleotides, etc)
What can happen to the acetyl CoA that is produced from pyruvate? Of these, where does it mostly go?
Where does most of the energy required by the liver come from?
What is the liver’s critical roles? [2]
TCA cycle for energy or fatty acid synthesis (mostly this)
Fatty acid and amino acid breakdown
Storing glucose and the generation of substrates that other tissues need
What hormone is secreted in fed state? In fast state? Where do these come from?
Fed = insulin, fast = glucagon, released by the islets of langerhans in the pancreas
Islets of langerhans - are they made up of endocrine or exocrine cells? What do the others do?
Which endocrine cell type releases insulin? And glucagon?
What is the physiological range of glucose? What happens to insulin secretion within this range?
Endocrine (exocrine secrete pancreatic enzymes into the pancreatic duct, and from there to the duodenum)
Insulin (Beta cells), glucagon (alpha cells)
4-7mM (lower below it, sudden increase between 4 to 7, tapering off, and no real increase at all at 15mM+)
How does the pancreatic beta cell work?
Blood glucose rises -> intercellular glucose level rises -> lots of ATP generated quickly -> closes potassium channels in membrane -> membrane potential depolarises (= less negative) -> this opens calcium channels -> insulin released
What stimulates insulin secretion?
What processes does this activate in regards to G6P and beyond? What is inhibited?
Increased blood glucose
It activates glycogen synthase (and so G6P is coverted to glycogen), increases conversion of G6P to pyruvate (and pyruvate to Acetyl CoA), and creation of fatty acids by fatty acid synthase. Breakdown of glycogen is inhibited, as is conversion of pyruvate to G6P
What stimulates glucagon secretion?
What does glucagon cause to occur? What happens to this molecule next? What is the name of the enzyme involved in sending glucose back into the blood?
Reduced blood glucose
Stimulates glucose breakdown to G1P (coverted to G6P). G6P can go in multiple directions (back to glycogen, on to pyruvate, on to the pentose phosphate pathway, or cleaved by glucose-6-phosphatase and released as glucose into the blood)
What counts as low plasma glucose? What is this called? Symptoms?
What counts at high plasma glucose? What is the pathology called? Symptoms?
<4mM. Hypoglycaemia: sweating, hunger, dizziness, fainting, irritability, eventual coma and death
> 7mM fasting levels. Diabetes: headache, thirst, excessive urination, blurred vision, eventual small vessel problems (leading to atherosclerosis, damaged kidneys, reduced circulation to extremities, etc)
Two ways glucose homeostasis is maintained?
Other than glucagon, what are other counter-regulatory hormones (protecting against hypoglycaemia)? [4]
Balance between uptake from blood into tissues (promoted by insulin -> glycogen production and triacylglycerol synthesis) and release from tissues into blood (promoted by glucagon -> glycogen breakdown, increased gluconeogenesis, and increased fat oxidisation to reduce glucose use)
Preferred utilization of other fuels (eg: fatty acids) by tissues that can use them
Adrenaline, noradrenaline, cortisol, growth hormone
[picture] Where do the separate aminos feed in for gluconeogenesis? For ketogenesis?
What effect does insulin (fed state) have on the processing of fatty acids for energy/storage?
What effect does glucagon (fasted state) have on the processing of fatty acids for energy/storage?
How is AMPK involved?
Stimulates Acetyl CoA Carboxylase to create Malonyl CoA (inhibits CPT-1 -> FAs accumulate & esterified to TAGs in cytosol)
Stimulates CPT-1 expression -> increases fatty acid transport to mitochondria (B-oxidation -> ketones/Acetyl CoA = energy!)
If AMP:ATP is high, it is activated -> inhibits Acetyl CoA Carboxylase -> less Malonyl CoA -> less inhibition of CPT-1 -> increases FA transport to mitochondria
Adipose tissue: In the fed state, what happens to extra glucose that arrives at the adipocytes?
Where does most fatty acid synthesis occur? How does it arrive at the adipocytes, and in what form? What enzymes are involved in transporting it inside, and what happens to it then?
Enters via GLUT4 (insulin-dependent). Converted via pyruvate to acetyl CoA (and from there to fatty acids -> TAG)
Liver, in VLDLs (as TAGs). Lipoprotein lipase breaks it down to fatty acids. They cross membranes, have CoA attached, and are esterified back to TAG.
Adipose tissue: what are the steps of remodeling (through obesity) that lead to the development of metabolic disease? What are the 6 resulting effects of this process?
What are the major fates of glucose in adipocytes?
Once free fatty acids have entered an adipocyte, where are they converted back into TAGs? What else is needed for this process to begin? What steps are there?
ER membrane (needs glycerol-3-phosphate): addition of two fatty acids to G3P (to phosphatidic acid), removal of phosphate, addition of last fatty acid
In fasting state, what enzyme breaks down TAGs to FAs? Which hormones stimulates this? What inhibits it?
Describe the process of activation
Triacylglycerol Lipase (adrenaline/glucagon stimulates, insulin inhibits)
Glucagon and adrenaline binds to glucagon or adrenergic receptors -> activates adenylate cyclase and increases cAMP -> cell signal to break apart TAGs at edge of lipid droplet
Layers of the muscle?
Reminder: enzyme in muscle that phosphorylates entering glucose? What enzyme builds up glycogen? What enzyme does it begin with? What is added at first? What disease is associated with defects in this enzyme?
Glucose uptake/glycogen production: What is phosphorylated when insulin binds to its receptor on muscles? What two things does this do?
How is AMPK involved?
Akt2 [which phosphorylates AS160, which then increases translocation of GLUT4 to membrane = increased glucose transport into muscles][also phosphorylates glycogen synthase kinase, which activates glycogen synthase, and production of glycogen]
High AMP:ATP = AMPK activates = inhibits GLUT4 recycling = more glucose can enter (to be converted to ATP and restore balance)
What are the primary fuels of resting muscles? Where are they from? What happens to them?
Free fatty acids from adipose tissue and ketones from liver - oxidised via acetyl CoA to produce ATP and carbon dioxide
What fuel sources does moderate exercise need in muscle? [3]
What occurs during maximally active muscle?
FAs, ketone bodies, and some glucose
Adrenaline stimulates glycogen breakdown to glucose-1 phosphate to glucose-6-phosphate -> no G6Pase so channelled to energy production -> broken down to lactase through glycolysis and lactose dehydrogenase (= 2ATP)
Fuels, products, and storage in liver/adipose tissue/skeletal muscle/brain…
What occurs in the early phase of starvation in regards to fuel molecules? [4 + details]
Glycogen -> glucose (liver), FAs released by adipocytes (oxidised in liver to Acetyl CoA, which enters TCA cycle and forms ATP, and also forms ketone bodies), muscles oxidise FAs for energy (low insulin), net breakdown of proteins in muslces (low insulin)
What are the hormones that stimulate glycogenolysis? What happens once they bind to their cellular receptors?
What are ketone bodies made from? What is provided when they are merged?
How many GTP and ATP are provided by ketone bodies?
How does the liver use ketone bodies? Why?
What are the ketone bodies? Which one is used for energy?
Two Acetyl CoA molecules (get back a CoA which can be used elsewhere)
2GTP + 22ATP (made in mitochondria)
It does not (lacks B-ketoacyl-CoA transferase enzyme)
Acetone and D-Beta-hydroxybutyrate (this one)
