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A recent study published in the American Journal of Preventive Medicine shows that keeping a food diary may double your weight loss efforts.
Homeostasis: the use of negative feedback loops to maintain body temperature and chemical composition relatively constant despite wide variations in food intake and environmental stress.
Why do alert and active animals store mainly fats, while sedentary plants store mainly carbohydrates? What are the principal "food" stores in the human body, and how are these used to protect the cerebral energy supply?
Note: neurotransmitter release from synaptic vesicles can be very fast, where there is a premium on speed. This seems so obvious that it is superfluous to mention it, except for the numerous misleading claims about regulatory systems that are actually close to equilibrium. Subcutaneous fat: the major fat depots are immediately beneath the skin, and packed around the viscera in the abdominal cavity. Great vessels above the heart: in healthy people about 70% of the blood normally resides within the veins, and red cells (erythrocytes) account for 40%-50% of the blood volume.
Cardiac muscle: has the highest metabolic rate in the human body, and achieves the highest arteriovenous oxygen extractions. Colon: (large intestine) is mainly responsible for the resorption of water from the faeces. Liver: is the major effector organ for the regulation of blood glucose and the processing of ingested food. It is more efficient to concentrate major metabolic activities in a small number of tissues.
Use the mouse to point at the tissues illustrated on the right, to review details of their metabolic activities under different physiological conditions.
Liver (L-type) and muscle (M-type) PFK subunits form mixed tetramers, but the genes are on separate chromosomes and their relative importance varies in different tissues.
In addition to the allosteric regulation by 5'AMP and citrate, PFK is strongly activated by fructose-2,6-bisphosphate which is produced by a second enzyme called phosphofructokinase-2 (PFK2). PFK2 is known as "tandem enzyme" because it also possesses fructose-2,6-bisphosphatase activity. The residual expression of FBPase in non-gluconeogenic tissues such as skeletal muscle suggests that some FBPase activity is important for normal PFK regulation. Insulin increases PFK gene expression in the longer term and PFK activity is depressed in type 1 diabetics. They all compare the current situation (or 'output') "C" with some 'desired' reference value "R" in order to generate an error signal "E". It is mobilised by adrenalin and glucagon, signalling via calcium ions and 3'5' cyclic AMP, but the total reserve is only sufficient for a few hours use. Hydroxybutyrate is an "honorary" ketone, because it is chemically related to acetoacetate, but it is in fact a secondary alcohol.


It is only possible to regulate reactions that would otherwise proceed spontaneously with a large negative ΔG. Fat cells arise from the fibroblast lineage, and consist of a central lipid droplet, surounded by a thin skin of active cytoplasm. Red cells have neither nucleus nor mitochondria, and their metabolism is restricted to a sluggish anaerobic glycolysis producing lactate and ATP. It is capable of limited amino acid metabolism and during fasting it releases mainly alanine and glutamine for further processing by the liver and the small intestine. Soluble compounds are delivered to the liver via the portal vein, while dietary fats are handled by the lymphatic drainage and delivered as chylomicrons into the left subclavian vein.
Resistant polysaccharides that escape digestion in the ileum are fermented by the colonic bacteria mainly to form butyrate, which can be absorbed and processed by the liver.
It is also responsible for the synthesis of numerous blood proteins, cholesterol and VLDL, ketone bodies, ureogenesis and the formation of bile. It is shown here in the relaxed position when the abdominal contents have compressed and emptied the lungs. It is protected from infection and environmental stress by the blood:brain barrier, which also prevents the access of large particles such as chylomicrons, VLDL and free fatty acids bound to serum albumin. This arrangement has been selected in all species, including humans, because specialisation permits higher local substrate concentrations and more rapid catalysis. First of all, write down what you think will happen, then review your answers from the screen.
This was one of the first allosteric enzymes to be discovered and it is a major control point for the glycolytic pathway.
The remainder of this discussion applies mainly to liver cells, where the gluconeogenic pathway may be in operation, via fructose-1,6-bisphosphatase (FBPase).
Conversely, fructose-1,6-bisphosphatase is inhibited by fructose-2,6-bisphosphate, which consequently sets the switch in favour of glycolysis, and blocks gluconeogenesis. The ratio between the two antagonostic enzyme activities is controlled by adrenalin and glucagon via adenyl cyclase, 3'5' cyclic AMP and protein kinase A. Newsholme has suggested that a low level of futile cycling may be important for effective regulation at low glycolytic fluxes, and allows the pathway to be controlled with much smaller excursions in the concentrations of the allosteric effectors. Fructose bisphosphatase and PFK are reciprocally regulated, and corticosteroids antagonise the insulin effects, although the detailed molecular mechanisms have yet to be elucidated.
Adipocytes provide the major energy store in humans, but muscle proteins are also degraded when food intake is inadequate. In practice food withdrawal may not be complete, and reduced physical activity lowers the fasting energy requirements. If a process has almost reached equilibrium regulation will make no difference to the outcome. In the fed state adipocytes respond strongly to circulating insulin with enhanced glucose uptake, associated with rapid glycolysis and the synthesis of triglyceride, thereby helping to stabilise the blood glucose concentration.


At least three muscle fibre types are recognised in clinical practice, whose proportions vary in different muscles. During fasting the ileum helps to convert glutamine released from skeletal muscle into blood glucose. There is a further advantage where most tissues are resting most of the time, because the available cardiac output, and hepatic support services (for example, lactate re-cycling) can be focussed towards "mission critical" activities which receive the lion's share of the available blood supply. Most amino acids [except for leucine and lysine] are glycogenic: their carbon skeletons can be converted (at least partially) into glucose via Krebs cycle intemediates.
Human beings have evolved to withstand a bad winter in a primitive hunter-gatherer society. Consider a large hydro-electric scheme: do we put the sluice gates in the in the concrete dam, or in the middle of the lake, or downstream on the way out to the sea?
The preferred substrates are free fatty acids and ketones, but heart muscle can also use triglycerides, lactate and even glucose if insulin is present. Type 1 fibres are rich in mitochondria and myoglobin and have an aerobic fat- or ketone-based metabolism. This helps to ensure a stable energy supply and to control the conversion of carbohydrates into Krebs cycle intermediates and fats, as explained in detail below. PFK and FBPase catalyse a potential futile cycle, and appropriate regulatory mechanisms are required. This enables adrenalin and glucagon to switch on gluconeogenesis in liver tissue and stablise the blood glucose concentration.
In biological systems the reference values are often encoded genetically, in the binding constants of proteins for their allosteric effectors.
Fatty acids cannot be be converted into glucose, but triglyceride droplets contain 6% by weight glycerol, which the liver converts into sugar phosphates.
In the fasting state adipocytes respond to circulating glucagon and adrenalin (and to noradrenalin released from local nerves) with rapid lipolysis catalysed by hormone-sensitive lipase followed by the release of free fatty acids and glycerol into the blood. They are fatigue resistant, have a slow twitch speed and are recruited first during physical activity. Receptors, ion-channels, second messengers and enzyme cascades provide the essential amplification for hormonal feedback loops. Type 2A fibres have a similar aerobic metabolism, but they are fast twitch, fatigue-resistant fibres which can use either fats or glucose.
They give the edge to athletic performance and are recruited in addition to the type 1 fibres when more effort is demanded. Type 2B fibres are fast contracting anaerobic fibres that are only recruited when a maximum effort is required.




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    07.03.2014