Metabolism 1 and 2 : Metabolism overview, carbohydrate metabolism Flashcards
What are the fates of acetyl CoA
Fatty acid synthesis and sterols
Citric acid cycle
Ketone bodies
Preferred fuels of liver
glucose, fatty acid oxidation, amino acids
Preferred fuels of adipose tissue
Fatty acids
Preferred fuels of skeletal muscle
At rest - beta oxidation (FA)
During exercise - glucose
Preferred fuels of heart muscle
Beta oxidation
Preferred fuels of brain
Glucose always, but in starvation it’ll use ketone bodies
Major carbohydrates and fuels in which they are found
Amylose (starch) Sucrose (table sugar, desert) Lactose (milk products) Fructose (fruit and honey) gluocse (fruit, honey) Maltose (barley) trehalose (mushroom) cellulose (plant walls)
What will happen if a person who is lactose intolerant eats milk?
This person is deficient in lactase - this is going to make lactase go through tract an led to osmotic diarrhea and co2 production from bacteria metabolising the lactose.
Carbohydrate metabolism pathways active in red blood cells
Glycolysis only - no mitochondria
Carbohydrate metabolism processes in brain
Glycolysis, TCA, ETC
Carbohydrate processes available to heart and skeletal muscle
Glycolysis, TCA, ETC, Glycogenolysis
Adipocytes
Conversion of glucose to fats
Hepatocytes
glycolysis, TCA, ETC, glycogenolysis, gluconeogenesis, pentose phosphate pathway
Glut2
Insulin independent transporter (liver)
High capacity, low affinity (almost never saturated)
Bidirectional
glut 4
insulin dependent transporter (low capacity, high affinity) - heart, skeletal muscle, adipocytes - not active in fasting states
SGLT1
will transport glucose or galactose with using sodium as a secondary active transport assistant
3 irreversible enzymes of glycolysis
hexokinase/glucokinase
phosphofructokinase 1
pyruvate kinase
Tissue localization: Hexokinase vs glucokinase
Hexokinase - everywhere
glucokinase - liver and pancreas technically
kinetic characteristics of hexokinase / glucokinase
Hexokinase - Low Km for glucose (constantly saturated)
Glucokinsae - High Km for glucose (rarely saturated)
Regulation of hexokinase / glucokinase
Hexokinase - constitutively active, constant amount, but allosterically regulated by its product, G6P
Glucokinase- shuttled between nucleus and cytosol for activity, F6P will suttle to nucleus and glucose brings to cytosol - this one is also inducible and will be induced by insulin to be synthesized
allosteric regulators of glucokinase and hexokinase
Hexokinase - allostericlally inhibited by glucose 6 phosphate
Glucokinase - allosterically activated by glucose, inactivated by fructose 6 phosphate
Allosteric regulation of phosphofuctokinase 1
Activators: F-2,6-BP, AMP, ADP (low energy, high glucose/ active PFK2)
Inhibitors: Citrate, ATP (high energy, glycolysis and TCA are going on)
Allosteric regulation of pyruvate kinase
Positive: F-1,6-BP (upstream)
Negative ATP, alanine
Covalent regulation of pyruvate kinase
Insulin –> dephosphorylated –> more active
Glucagon/ epinephrine –> phosphorylated –> less active
Hepatic PFK2 is phosphorylated in the ___ domain when glucagon and epinephrine are around, meaning __________.
Kinase
It going to have phosphatase activity going (you will not have F-2,6 BP and glycolysis is inhibited)
Muscle PFK2 is going to be phosphorylated in -____ domain in presence of epinephrine? Meaning _____ about its activity
phosphatase
You get a lot of F-2,6-BP, glycolysis is going to be active
What pancreatic hormone inhibits hepatic glycolysis
Glucagon
How does glucagon affect hepatic glycolysis?
Inhibit enzymes (PFK1 via PFK2 being put in “phosphatase mode”, pyruvate kinase), and also decrease enzyme synthesis (glucokinase, PFK1, pyruvate kinase)
How does epinephrine inhibit hepatic glycolysis but promote muscle glycolysis
differential pFK2 covalent modifications
Hepatic –> kinase phosphorylation (inactivates kinase)
muscle –> phosphatase phosphorylation (inactivates phosphatase)
When will lactate –> pyruvate and acetyl coA
When there is extensive NAD - also in tissues with LDH that favors the lactate –> pyruvate conversion (like heart, instead of skeletal muscle which would prefer pyruvate –> lactate)
heart LDH isozyme
LDH4 (favors making pyruvate)
Skeletal muscle LDH isozyme
LDH5 M4 (favors lactate)
negative regulators of PDH
NADH, Acetyl CoA
Positive regulators of PDh
CoASH, NAD+, ADP, pyruvate, magnesium, calcium
Is PDH active or inactive when phosphorylated
Inactive
Vitamin cofactors that participate in reactions catalyzed by pdh
riboflavin, niacin, thiamine
Arsenic poisoning does what to pdh activity
fucks it up
Genetic deficiency in fructose aldolase
Intracellular trapping of F1P is result –> decline in inorganic phosphate and inability to make ATP –> absolutely must avoid fructose
galactokinase or galactose 1 phosphate uridyl transferase deficiencies, what food should people avoid
avoid lactose at all costs
galactokinase deficiency – you get diarrhea, can’t utilize galactose
galactose 1 uridyl transferase deficiency is bad , you trap sugar phosphates and die
