MBC - Integration Of Metabolism Flashcards
Energy intake and expenditure - general
Tightly coordinated, different based on tissue
Energy intake and expenditure - brain
2% of body weight, 20% of resting body energy, continuous glucose supply, cannot metabolize fatty acids, ketone bodies (ie beta hydroxybutyrate) can partially sub for glucose, hypoglycaemia = faintness and coma, hyperglycaemia = irreversible damage
Energy intake and expenditure - skeletal muscle
40% of body weight, ATP requirements vary depending on exercise, light contraction requirements met by oxidative phosphorylation, vigorous contraction oxygen becomes limiting factor so glycogen breakdown and lactate formation
Energy intake and expenditure - heart
1% total body weight, 10% resting metabolic rate, completely aerobic metabolism, rich in mitochondria, TCA cycle substrate (free fatty acids (FFA), ketone bodies…), loss of oxygen = cell death and myocardial infarction
Energy intake and expenditure - liver
Highly metabolically active, can inter convert nutrient types, maintain [blood glucose] at 4.0 - 5.5 mM, glycogen store, lipoprotein metabolism (transport of triglycerides and cholesterol), transamination, >20% metabolic rate, 2.5% body weight
Energy intake and expenditure - adipose tissue
15% total body weight, long term storage site for FA as triglycerides
Gluconeogenesis
If plasma glucose level falls below 3 mM then hypoglycaemic coma (to avoid breakdown of glycogen, release FFAs from adipose tissue, convert acetyl CoA into ketone bodies via liver, both FA and ketone bodies used by muscle so more glucose available for brain, exhausted after 12-18hrs so gluconeogenesis), overall pathway aim: glucose from pyruvate, 3 essentially irreversible reactions catalysed by hexokinase + phosphofructokinase + pyruvate kinase, 4 additional high energy bonds required to make it energetically favourable (+90 to -38 kJ/mol)
Proteins and fats as energy sources
Deamination gives rise to 7 molecules (pyruvate, acetyl CoA, acetoacetyl CoA, alpha-ketoglutarate, succinyl CoA, fumerate and oxaloacetate), urea lost as waste product, glucogenic amino acids because can give rise to glucose via gluconeogenesis, ketogenic amino acids = skeletons for FAs and ketone bodies, triglycerides broken down into FAs + glycerol (can be converted to DHAP (dihydroxyacetone phosphate) and enter glucogenic pathway upstream), not fatty acids (no synthesis of oxaloacetate/pyruvate from acetyl CoA (2C atoms enter TCA cycle as acetyl CoA by combining with oxaloacetate to form citrate, as cycle progresses 2C lost sequentially as Co2 before oxaloacetate eventually eventually regenerated))
Aerobic respiration
As muscle contracts ATP demand by actomyosin & cation balance increases, increased number of glucose transporters on muscle cells membranes, adrenaline increases rate of glycolysis in muscle, increasing rate of gluconeogenesis by liver + release of FA from adipocytes
Anaerobic respiration
Glycogen within muscle broken down to meet energetic demands, to replenish NAD+ levels and maintain glycolysis, pyruvate taken up by liver and converted into lactate by lactate dehydrogenase, lactate can then be used by liver to generate glucose by gluconeogenesis
Control of metabolic pathways - general
Typically centred around irreversible steps (at these points, increases in enzyme activity greatly increases rate of downstream steps) for greatest levels of control, preferable for these steps to be early in pathway, product inhibition and hormones
Control of metabolic pathways - glucose metabolism
Km of hexokinase I indicates it is active at low concentrations of glucose and is essentially operating operating at Vmax at all times, sensitive to G6P inhibition (under anaerobic conditions when TCA cycle rate drops, glycolysis slows, hex I is inhibited by accumulating G6P), glucose-6-phosphate (found in liver but not in muscle can catalyse reverse reaction to hex I generating glucose from G6P
Hormonal control of blood glucose
Islets of pancreas = insulin (stimulates uptake and use of glucose and storage as glycogen + fat), glucagon (stimulates production of glucose by gluconeogenesis and glycogen + fat breakdown), adrenaline (aka epinephrine), glucocorticoids (steroid hormones, increase synthesis of metabolic enzymes concerned with glucose availability)
Diabetes mellitus
Disorder of insulin release and signalling resulting in impaired regulate blood glucose, type I (beta-cell dysfunction) and type II (insulin resistance)
