Essentially all of the energy of isometric contractions appears as heat, because little or no external work (force multiplied by the distance that the force moves a mass) is done. Energy is stored by forming energy-rich compounds. The amount of energy storage varies, but in fasting individuals it is zero or negative. Therefore, in an adult individual who has not eaten recently and who is not moving (or growing, reproducing, or lactating), all of the energy output appears as heat. Calorimetry The energy released by combustion of foodstuffs outside the body can be measured directly (direct calorimetry) by oxidizing the compounds in an apparatus such as a bomb calorimeter, a metal vessel surrounded by water inside an insulated container. The food is ignited by an electric spark. The change in the temperature of the water is a measure of the calories produced. Similar measurements of the energy released by combustion of compounds in living animals and humans are much more complex, but calorimeters have been constructed that can physically accommodate human beings. The heat produced by their bodies is measured by the change in temperature of the water in the walls of the calorimeter. The caloric values of the common foodstuffs, as measured in a bomb calorimeter, are found to be 4.1 kcal/g of carbohydrate, 9.3 kcal/g of fat, and 5.3 kcal/g of protein. In the body, similar values are obtained for carbohydrate and fat, but the oxidation of protein is incomplete, the end products of protein catabolism being urea and related nitrogenous compounds in addition to CO2 and H2O (see below). Therefore, the caloric value of protein in the body is only 4.1 kcal/g. Indirect Calorimetry Energy production can also be calculated by measuring the products of the energy-producing biologic oxidations—ie, CO2, H2O, and the end products of protein catabolism produced—but this is difficult. However, O2 is not stored, and except when an O2 debt is being incurred, the amount of O2 consumption per unit of time is proportionate to the energy liberated by metabolism. Consequently, measurement of O2 consumption (indirect calorimetry) is used to determine the metabolic rate. Respiratory Quotient (RQ) The respiratory quotient (RQ) is the ratio in the steady state of the volume of CO2 produced to the volume of O2 consumed per unit of time. It should be distinguished from the respiratory exchange ratio (R), which is the ratio of CO2 to O2 at any given time whether or not equilibrium has been reached. R is affected by factors other than metabolism. RQ and R can be calculated for reactions outside the body, for individual organs and tissues, and for the whole body. The RQ of carbohydrate is 1.00, and that of fat is about 0.70. This is because H and O are present in carbohydrate in the same proportions as in water, whereas in the various fats, extra O2 is necessary for the formation of H2O. Determining the RQ of protein in the body is a complex process, but an average value of 0.82 has been calculated. The approximate amounts of carbohydrate, protein, and fat being oxidized in the body at any given time can be calculated from the RQ and the urinary nitrogen excretion. RQ and R for the whole body differ in various conditions. For example, during hyperventilation, R rises because CO2 is being blown off. During severe exercise, R may reach 2.00 because CO2 is being blown off and lactic acid from anaerobic glycolysis is being converted to CO2 (see below). After exercise, R may fall for a while to 0.50 or less. In metabolic acidosis, R rises because respiratory compensation for the acidosis causes the amount of CO2 expired to rise. In severe acidosis, R may be greater than 1.00. In metabolic alkalosis, R falls. The O2 consumption and CO2 production of an organ can be calculated at equilibrium by multiplying its blood flow per unit of time by the arteriovenous differences for O2 and CO2 across the organ, and the RQ can then be calculated. Data on the RQ of individual organs are of considerable interest in drawing inferences about the metabolic processes occurring in them. For example, the RQ of the brain is regularly 0.97-0.99, indicating that its principal but not its only fuel is carbohydrate. During secretion of gastric juice, the stomach has a negative R because it takes up more CO2 from the arterial blood than it puts into the venous blood
Large animals have higher absolute BMRs, but the ratio of BMR to body weight in small animals is much greater. One variable that correlates well with the metabolic rate in different species is the body surface area. This would be expected, since heat exchange occurs at the body surface. The actual relation to body weight (W) would be However, repeated measurements by numerous investigators have come up with a higher exponent, averaging 0.75. Thus, the slope of the line relating metabolic rate to body weight is steeper than it would be if the relation were due solely to body area. The cause of the greater slope has been much debated but remains unsettled.
For example, catabolism of 1 mol of a six-carbon fatty acid through the citric acid cycle to CO2 and H2O generates 44 mol of ATP, compared with the 38 mol generated by catabolism of 1 mol of the six-carbon carbohydrate glucose.
Two of the three ketone bodies, acetoacetate and β-hydroxybutyrate, are anions of the moderately strong acids acetoacetic acid and β-hydroxybutyric acid. Many of their protons are buffered, reducing the decline in pH that would otherwise occur. However, the buffering capacity can be exceeded, and the metabolic acidosis that develops in conditions such as diabetic ketosis can be severe and even fatal. Three conditions lead to deficient intracellular glucose supplies: starvation, diabetes mellitus, and a high-fat, low-carbohydrate diet. In diabetes, glucose entry into cells is impaired. When most of the caloric intake is supplied by fat, carbohydrate deficiency develops because there is no major pathway for converting fat to carbohydrate. The liver cells also become filled with fat, which damages them and displaces any glycogen that is formed. In all of these conditions, ketosis develops primarily because the supply of ketones is overabundant. The acetone odor on the breath of children who have been vomiting is due to the ketosis of starvation. Parenteral administration of relatively small amounts of glucose abolishes the ketosis, and it is for this reason that carbohydrate is said to be antiketogenic.
http://www.theatlantic.com/health/archive/2013/03/study-mummies-have-atherosclerosis-too/273863/ http://blogs.unimelb.edu.au/sciencecommunication/2013/08/13/mummies-return-is-a-reality-we-need-more-mummy-hunters/ Put more colorfully, &quot;We found that heart disease is a serial killer that has been stalking mankind for thousands of years,&quot; one of the study&apos;s lead authors, Randall Thompson, said in a statement. In modern men and women over the age of 50, the condition&apos;s prevalence is as high as 82 and 68 percent, respectively. And certain behaviors certainly increase this risk -- these findings in fact emphasize the importance of controlling for those factors, like diet, that are indeed controllable. As with last summer&apos;s counter-intuitive findings that sedentary office workers burn as many calories in a day as modern hunter-gatherers, this should at the very least make us question whether the good old days of pre-modern living were as ideal as we tend to imagine them.
Dyslipidemia (or dyslipoproteinemia) refers to abnormal concentrations of serum lipoproteins as defined by the Third Report of the National Cholesterol Education Program. It is estimated that nearly half of the U.S. population has some form of dyslipidemia, especially among white and Asian populations. These abnormalities are the result of a combination of genetic and dietary factors. Primary or familial dyslipoproteinemias result from genetic defects that cause abnormalities in lipid-metabolizing enzymes and abnormal cellular lipid receptors. Secondary causes of dyslipidemia include several common systemic disorders, such as diabetes, hypothyroidism, pancreatitis, and renal nephrosis, as well as the use of certain medications such as certain diuretics, beta-blockers, glucocorticoids, interferons, and antiretrovirals.
Physical signs of heterozygous familial hypercholesterolemia (HeFH), which result from cholesterol deposited within macrophages in specific sites. Tendinous xanthomas, for example, manifest first as thickening of, and later as deposits within, extensor tendons. A: Lateral borders of thickened Achilles&apos; tendons are shown with arrows. B: Tendinous xanthomas can also occur in the extensor tendons of the hands (shown), feet, elbows and knees. C: Xanthelasmas are cholesterol deposits in the eyelids. D: Arcus cornealis results from cholesterol infiltration around the corneal rim (arrow). Deposits in and around the eye tend to be more specific for HeFH in people younger than 45 years; in elderly people, they are less likely to be associated with blood lipoprotein abnormalities, for instance in the case of arcus senilis. Some patients may report having observed cutaneous cholesterol deposition in response to a functional enquiry. People with HeFH have been known to undergo cosmetic eyelid surgery to remove xanthelasmas — even repeatedly, for lesions that continued to recur — without ever having had their plasma lipoprotein profiles determined.
Obesity is a problem because of its complications. It is associated with accelerated atherosclerosis and an increased incidence of gallbladder and other diseases. Its association with type 2 diabetes is especially striking. As weight increases, insulin resistance increases and frank diabetes appears. At least in some cases, glucose tolerance is restored when weight is lost.The causes of the high incidence of obesity in the general population are probably multiple. Studies of twins raised apart show that there is a definite genetic component. It has been pointed out that through much of human evolution, famines were common, and mechanisms that permitted increased energy storage as fat had survival value. Now, however, food is plentiful in many countries, and the ability to gain and retain fat has become a liability. As noted above, the fundamental cause of obesity is still excess of energy intake in food over energy expenditure. If human volunteers are fed a fixed high-calorie diet, some gain weight more rapidly than others, but the slower weight gain is due to increased energy expenditure in the form of small, fidgety movements (nonexercise activity thermogenesis; NEAT). Body weight generally increases at a slow but steady rate throughout adult life. Decreased physical activity is undoubtedly a factor in this increase, but decreased sensitivity to leptin may also play a role.
PATHOGENESIS. The lipid storing cells, adipocytes comprise the adipose tissue, and are present in vascular and stromal compartment in the body. Besides the generally accepted role of adipocytes for fat storage, these cells also release endocrine-regulating molecules. These molecules include: energy regulatory hormone (leptin), cytokines (TNF-α and interleukin-6), insulin sensitivity regulating agents (adiponectin, resistin and RBP4), prothrombotic factors (plasminogen activator inhibitor), and blood pressure regulating agent (angiotensingen). Adipose mass is increased due to enlargement of adipose cells due to excess of intracellular lipid deposition as well as due to increase in the number of adipocytes. The most important environmental factor of excess consumption of nutrients can lead to obesity. However, underlying molecular mechanisms of obesity are beginning to unfold based on observations that obesity is familial and is seen in identical twins. Recently, two obesity genes have been found: ob gene and its protein product leptin, and db gene and its protein product leptin receptor.
Obesity is the most common and most expensive nutritional problem in the USA. A convenient and reliable indicator of body fat is the body mass index (BMI), which is the body weight (in kilograms) divided by the square of the height (in meters). Values above 25 are abnormal. Individuals with values of 25-30 are overweight, and those with values &gt; 30 are obese. In the USA, 55% of the population are overweight and 22% are obese. The incidence of obesity is also increasing in other countries. Indeed, the Worldwatch Institute has estimated that although starvation continues to be a problem in many parts of the world, the number of overweight people in the world is now as great as the number of underfed.
MMeettaabboolliicc RRaattee -- tthe amount of energy liberated per unit of time.
The amount of energy liberated by the catabolism of food in the body is the
same as the amount liberated when food is burned outside the body.
The energy liberated by catabolic processes in the body is used for
maintaining body functions, digesting and metabolizing food,
thermoregulation, and physical activity. It appears as external work, heat,
and energy storage:
= + +
Isotonic muscle contractions perform work at a peak efficiency
WWOORRKK DDOONNEE TTOOTTAALL EENNEERRGGYY
TThhee ssttaannddaarrdd uunniitt ooff hheeaatt eenneerrggyy iiss tthhee ccaalloorriiee ((ccaall)),, ddeeffiinneedd aass tthhee aammoouunntt
ooff hheeaatt eenneerrggyy nneecceessssaarryy ttoo rraaiissee tthhee tteemmppeerraattuurree ooff 11 gg ooff wwaatteerr 11 ddeeggrreeee,,
ffrroomm 1155 °°CC ttoo 1166 °°CC.. TThhiiss uunniitt iiss aallssoo ccaalllleedd tthhee ggrraamm ccaalloorriiee,, ssmmaallll ccaalloorriiee,,
oorr ssttaannddaarrdd ccaalloorriiee.. TThhee uunniitt ccoommmmoonnllyy uusseedd iinn pphhyyssiioollooggyy aanndd mmeeddiicciinnee iiss
tthhee CCaalloorriiee ((kkiillooccaalloorriiee;; kkccaall)),, wwhhiicchh eeqquuaallss 11000000 ccaall..
Transports diet-derived triglyceride (TG) in the blood
(1) Protein (2%); (2) TG (87%); (3) Cholesterol (CH;3%); (4) Phospholipid (8%)
Synthesized in intestinal epithelium
(1) Requires apolipoprotein (apo) B-48 for assembly and secretion
(2) Nascent chylomicrons in the circulation obtain apo C-Il and apo E from high
density lipoprotein (HDL)
Absent during fasting
If increased, it forms a creamy supranate.
• 1) Test tube must be left upright in a refrigerator overnight,
• 2) Chylomicron floats on top of plasma because it has very little protein (low
Source of fatty acids and glycerol
• Used to synthesize TG in the liver and adipose
Hydrolysis by capillary lipoprotein lipase (CPL) leaves a chylomicron remnant,
• Chylomicron remnants arc removed by apo E receptors in the liver.
Lipoprotein Functions Apoproteins Functions
Transport dietary triglyceride and
cholesterol from intestine to
Secreted by intestine
Activates lipoprotein lipase
Uptake of remnants by the
Transports triglyceride from liver
Secreted by liver
Activates lipoprotein lipase
Uptake of remnants (IDL) by
Picks up cholesterol from HDL to
Picked up by liver
Uptake by liver
Delivers cholesterol into cells ApoB-100 Uptake by liver and other
tissues via LDL receptor
Picks up cholesterol accumulating
in blood vessels
Delivers cholesterol to liver and
steroidogenic tissues via
scavenger receptor (SR-B1)
Shuttles apoC-II and apoE in
apoA-1 Activates lecithin cholesterol
acyltransferase (LCAT) to
produce cholesterol esters
Transports liver-synthesized TG in the blood
- Requires apolipoprotein B-100 for assembly and secretion
• (1) Protein (9%); (2) TG (55%); (3) CH (17%); (4) Phospholipid (19%).
Source of fatty acids and glycerol
• 1) Used to synthesize TG in the adipose tissue
• 2) Hydrolysis by CPL produces intermediate-density lipoprotein (IDL) and low density
• 3) Some of the IDL is removed from blood by apo E receptors in the liver.
Cholesterol ester transport protein (CETP)
(1) Transfers CH from HDL to VLDL;
(2) Transfers TG from VLDL to HDL;
(3) An increase in VLDL always causes a decrease in HDL-CH.
If increased, it forms a creamy infranate.
• Note that the protein is greater in VLDL than in chylomicrons, so it sinks rather than floats in
• (1) Optimal level < 150 mg/dL
• (2) Borderline high level 150 to 199 mg/dL
• (3) High level 200 to 499 mg/dL,
• (4) Very high level > 500 mg/dL
• Increased by exercise, wine, estrogen
Composition: 1) Protein (50%); 2) TG (3%; unless VLDL is increased); 3) CH (20%);
4) Phospholipid (27%)
Synthesized by the liver and small intestine
Functions of HDL
1) Source of apolipoproteins for other lipoprotein fractions
2) Removes cholesterol from atherosclerotic plaques
a) Delivers CH from peripheral tissue to the liver
b) CH is either excreted into bile or converted into bile acids/salts.
Measured in the laboratory as HDL-CH
1) Inverse association of levels of HDL-CH and incidence and prevalence of CHD
2) Decreased if VLDL is increased
3) Ranges of HDL-CH
(a) High level (optimal) ≥ 60 g/dL
(b) Low level (suboptimal) < 40 mg/dL
4) Fasting is not required for an accurate serum HDL-CH.
Same reason as for serum CH.
In many tissues, aacceettyyll--CCooAA uunniittss condense to ffoorrmm aacceettooaacceettyyll--CCooAA.
In the lliivveerr, which (unlike other tissues) ccoonnttaaiinnss aa ddeeaaccyyllaassee, free aceto-acetate is formed.
This ββ--kkeettoo aacciidd is converted to ββ--hhyyddrrooxxyybbuuttyyrraattee and aacceettoonnee, and because these
compounds are metabolized with difficulty in the liver, they diffuse into the circulation.
AAcceettooaacceettaattee is also formed in the liver via the formation of 3-hydroxy-3-methylglutaryl-CoA,
and this pathway is quantitatively more important than deacylation.
AAcceettooaacceettaattee, ββ--hhyyddrrooxxyybbuuttyyrraattee, and aacceettoonnee are called kkeettoonnee bbooddiieess ((KKBB)).
Tissues other than liver transfer CoA from succinyl-CoA to acetoacetate and metabolize the
"active" acetoacetate to CO2 and H2O via the citric acid cycle. There are also other pathways
whereby ketone bodies are metabolized.
AAcceettoonnee is discharged in the urine and expired air.
The normal blood ketone level in humans is low (about 1 mg/dL) and less than 1 mg is
excreted per 24 hours, because the ketones are normally metabolized as rapidly as they are
formed. However, if the eennttrryy ooff aacceettyyll--CCooAA iinnttoo tthhee cciittrriicc aacciidd ccyyccllee iiss ddeepprreesssseedd because of a
ddeeccrreeaasseedd ssuuppppllyy ooff tthhee pprroodduuccttss ooff gglluuccoossee mmeettaabboolliissmm, or if the entry does not increase
when the supply of acetyl-CoA increases, acetyl-CoA accumulates, the rate of condensation to
acetoacetyl-CoA increases, and mmoorree aacceettooaacceettaattee iiss ffoorrmmeedd iinn tthhee lliivveerr.
The ability of the tissues to ooxxiiddiizzee tthhee kkeettoonneess is soon exceeded, and they accumulate in the
KKBB iinn uurriinnee AAcceettoonnee bbrreeaatthh
KKBB iinn tthhee bblloooodd
•Role of blood monocytes. Though blood monocytes do
not possess receptors for normal LDL, LDL does appear in
the monocyte cytoplasm to form foam cell. Plasma LDL on
entry into the intima undergoes oxidation. The ‘oxidised
LDL’ formed in the intima performs the following all-important
functions on monocytes and endothelium:
•For monocytes: Oxidised LDL acts to attract, proliferate,
immobilise and activate them as well as is readily taken up
by scavenger receptor on the monocyte to transform it to a
lipid-laden foam cell.
•For endothelium: Oxidised LDL is cytotoxic.
•Death of foam cell by apoptosis releases lipid to form lipid
core of plaque.
Endothelial Dysfunction in Atherosclerosis
Ross R. N Engl J Med 1999; 340:115–126.
Macrophages play main
1. They have “scavenger”-
receptors so cholesterol
comes in macrophage
only due to concentration
2. They can accumulate a
lot of Chl inside (this
process is controlled by
3. Changed LDLP
Fatty-Streak Formation in
Ross R. N Engl J Med 1999; 340:115–126.
Formation of an Advanced,
Complicated Lesion in
Ross R. N Engl J Med 1999; 340:115–126.
(because they are the
SMC migration in intimae
collagen and elastin
injured vessel wall
44 ssttaaggee --
(due to endothelium
(necrosis of and
causes damage of
(deposit of insoluble