Carnitine was detected at the beginning of this century, but it was nearly forgotten among biochemists until its importance in fatty acid metabolism was established 50 years later. In the last 30 years, interest in the metabolism and functions of carnitine has steadily increased. Carnitine is synthesized in most eucaryotic organisms, although a few insects (and most likely some newborn animals) require it as a nutritional factor (vitamin BT). Carnitine biosynthesis is initiated by methylation of lysine. The trimethyllysine formed is subsequently converted to butyrobetaine in all tissues; the butyrobetaine is finally hydroxylated to carnitine in the liver and, in some animals, in the kidneys (see Fig. 1). It is released from these tissues and is then actively taken up by all other tissues. The turnover of carnitine in the body is slow, and the regulation of its synthesis is still incompletely understood. Microorganisms (e.g., in the intestine) can metabolize carnitine to trimethylamine, dehydrocarnitine (b...

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Carnitine--metabolism and functions

Utilization of carbohydrate and fatty acids is strongly influenced by rates of con­ sumption and production of high energy compounds in cardiac muscle. In well­ oxygenated hearts, fatty acid has been identified as the preferred substrate by both in vivo and in vitro studies (for review see 146). Availability of fatty acid suppresses glucose utilization by inhibition of several steps in the glycolytic pathway. Since a variety of longand short-chained fatty substrates are inhibitory and since the effect is abolished in hearts perfused under anaerobic conditions, oxidation of the fatty acid appears to be required for this effect. When energy utilization of well­ oxygenated hearts is increased, consumption of fatty acids and/or glucose is ac­ celerated. Under these conditions, fatty acids remain the preferred oxidative substrate. Availability of oxygen to the heart can be restricted either by lowering or reducing to zero the oxygen tension of the perfusate, thereby inducing hypoxia or anoxia, or by restricting the flow of perfusate containing high oxygen tensions to induce ischemia. In hypoxic or anoxic hearts, fatty acid oxidation is suppressed and glycol­ ysis is stimulated. The acceleration of flux through glycolysis may be as much as 10to 20-fold. On the other hand, ischemia results in only a transient increase in glycolytic flux that is followed within 3-4 min by inhibition. Fatty acid oxidation is suppressed in ischemic hearts leading to accumulation of long-chained CoA derivatives and increase in triglyceride levels.

Relationship Between Carbohydrate and Lipid Metabolism and the Energy Balance of Heart Muscle

Skeletal muscle adaptability : Significance for metabolism and performance

The sections in this article are:


1
Motor Unit
1.1
Fibers per Motor Unit

1.2
Contractile Properties

1.3
Biochemical Basis for Differences in Twitch Properties

1.4
Histochemical Differentiation of Muscle Fibers

1.5
Ultrastructural Basis for Skeletal Muscle Fiber Typing

1.6
Maximal Contractile Force

1.7
Speed of Contraction

1.8
Fatigue Characteristics

1.9
Metabolic Characteristics

1.10
Ionic Composition of Skeletal Muscle

1.11
Summary




2
Muscle Fiber Composition in Human Skeletal Muscle

3
Motor-Unit Recruitment

4
Adaptive Response in Skeletal Muscle
4.1
Muscle Size

4.2
Metabolic Capacity




5
Connective Tissue

6
Capillaries
6.1
Methodology

6.2
Anatomy

6.3
Capillary Density

6.4
Capillary Length and Diameter

6.5
Use and Disuse

6.6
Regulation




7
Significance of Adaptation
7.1
Muscular Size

7.2
Substrate Stores

7.3
Enzyme Activities

7.4
Summary

Skeletal Muscle Adaptability: Significance for Metabolism and Performance

Cellular and molecular diversities of mammalian skeletal muscle fibers

1. The maximum activities of hexokinase, phosphorylase and phosphofructokinase have been measured in extracts from a variety of muscles and they have been used to estimate the maximum rates of operation of glycolysis in muscle. These estimated rates of glycolysis are compared with those calculated for the intact muscle from such information as oxygen uptake, glycogen degradation and lactate formation. Reasonable agreement between these determinations is observed, and this suggests that such enzyme activity measurements may provide a useful method for comparative investigations into quantitative aspects of maximum glycolytic flux in muscle. 2. The enzyme activities from insect flight muscle confirm and extend much of the earlier work and indicate the type of fuel that can support insect flight. The maximum activity of hexokinase in some insect flight muscles is about tenfold higher than that in vertebrate muscles. The activity of phosphorylase is greater, in general, in vertebrate muscle (particularly white muscle) than in insect flight muscle. This is probably related to the role of glycogen breakdown in vertebrate muscle (particularly white muscle) for the provision of ATP from anaerobic glycolysis and not from complete oxidation of the glucose residues. The activity of hexokinase was found to be higher in red than in white vertebrate muscle, thus confirming and extending earlier reports. 3. The maximum activity of the mitochondrial glycerophosphate dehydrogenase was always much lower than that of the cytoplasmic enzyme, indicating that the former enzyme is rate-limiting for the glycerol 3-phosphate cycle. From the maximum activity of the mitochondrial enzyme it can be calculated that the operation of this cycle would account for the reoxidation of all the glycolytically produced NADH in insect flight muscle but it could account for only a small amount in vertebrate muscle. Other mechanisms for this NADH reoxidation in vertebrate muscle are discussed briefly.

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The activities of phosphorylase, hexokinase, phosphofructokinase, lactate dehydrogenase and the glycerol 3-phosphate dehydrogenase in muscles from vertebrates and invertebrates

1. The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in crude homogenates of vertebrate and invertebrate muscles are reported. 2. Pyruvate carboxylase activity was present in all insect flight muscles that were investigated: in homogenates of bumble-bee flight muscle the activity was inhibited by ADP and activated by acetyl-CoA, and it was distributed mainly in the mitochondrial fraction. This is the first demonstration of pyruvate carboxylase activity in muscle. However, the activity appears to be restricted to insect flight muscle, since it was not found in other invertebrate or vertebrate muscles. 3. Since the three enzymes were never found together in the same muscle, it is concluded that these enzymes cannot provide a pathway for the synthesis of glycogen from lactate or pyruvate in muscle. Other roles for these enzymes in muscle are suggested. In particular, pyruvate carboxylase may be present in insect flight muscle for the provision of oxaloacetate to support the large increase in activity of the tricarboxylic acid cycle which occurs when an insect takes flight.

The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in muscles from vertebrates and invertebrates.

1. The maximum catalytic activities of fructose diphosphatase from flight muscles of bumble-bees (Bombus spp.) are at least 30-fold those reported for the enzyme from other tissues. The maximum activity of fructose diphosphatase in the flight muscle of any particular bee is similar to that of phosphofructokinase in the same muscle, and the activity of hexokinase is similar to or greater than the activity of phosphofructokinase. There is no detectable activity of glucose 6-phosphatase and only a very low activity of glucose 6-phosphate dehydrogenase in these muscles. The activities of both fructose diphosphatase and phosphofructokinase vary inversely with the body weight of the bee, whereas that of hexokinase is relatively constant. 2. There is no significant hydrolysis of fructose 1-phosphate, fructose 6-phosphate, glucose 1,6-diphosphate and glycerol 3-phosphate by extracts of bumble-bee flight muscle. 3. Fructose 1,6-diphosphatase from bumble-bee flight muscle and from other muscles is inhibited by Mn(2+) and univalent cations; the potency of inhibition by the latter varies in the order Li(+)>Na(+)>K(+). However, the fructose diphosphatase from bumble-bee flight muscle is different from the enzyme from other tissues in that it is not inhibited by AMP. 4. The contents of ATP, hexose monophosphates, fructose diphosphate and triose phosphates in bumble-bee flight muscle showed no significant changes between rest and flight. 5. It is proposed that both fructose diphosphatase and phosphofructokinase are simultaneously active and catalyse a cycle between fructose 6-phosphate and fructose diphosphate in resting bumble-bee flight muscle. Such a cycle would produce continuous hydrolysis of ATP, with the release of energy as heat, which would help to maintain the thoracic temperature during rest periods at a level adequate for flight.

/pdf/the-activities-of-fructose-diphosphatase-in-flight-muscles-16dzr3bke4.pdf

The activities of fructose diphosphatase in flight muscles from the bumble-bee and the role of this enzyme in heat generation.

1. The activities of tri-, di- and mono-glyceride lipase and carnitine palmitoyltransferase were measured in homogenates of a variety of muscles. These activities were used to estimate the rate of utilization of glycerides and fatty acids by muscle. In muscles whose estimated rates of fat utilization can be compared with rates calculated for the intact muscle from such information as O2 uptake, there is reasonable agreement between the estimated and calculated rates. 2. In all muscles investigated the maximum rates of hydrolysis of glycerides increase in the order triglyceride, diglyceride, monoglyceride. The activity of diglyceride lipase is highest in the flight muscles of insects such as the locust, waterbug and some moths and is lowest in the flight muscles of flies, bees and the wasp. These results are consistent with the utilization of diglyceride as a fuel for some insect flight muscles. 3. In many muscles from both vertebrates and invertebrates the activity of glycerol kinase is similar to that of lipase. It is concluded that in these muscles the metabolic role of glycerol kinase is the removal of glycerol produced during lipolysis. However, in some insect flight muscles the activity of glycerol kinase is much greater than that of lipase, which suggests a different role for glycerol kinase in these muscles.

/pdf/the-activities-of-lipases-and-carnitine-palmitoyl-2czw7u33ju.pdf

The activities of lipases and carnitine palmitoyl-transferase in muscles from vertebrates and invertebrates

/pdf/the-importance-of-alpha-glycerophosphate-oxidase-in-lo3sam7zog.pdf

The importance of alpha-glycerophosphate oxidase in oxidation of extramitochondrial reduced nicotinamide-adenine dinucleotide in vertebrate and insect muscle.

B. Crabtree

Papers

The activities of phosphorylase, hexokinase, phosphofructokinase, lactate dehydrogenase and the glycerol 3-phosphate dehydrogenase in muscles from vertebrates and invertebrates

The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase and fructose diphosphatase in muscles from vertebrates and invertebrates.

The activities of fructose diphosphatase in flight muscles from the bumble-bee and the role of this enzyme in heat generation.

The activities of lipases and carnitine palmitoyl-transferase in muscles from vertebrates and invertebrates

The importance of alpha-glycerophosphate oxidase in oxidation of extramitochondrial reduced nicotinamide-adenine dinucleotide in vertebrate and insect muscle.