Nutrition

·         Dietary Reference Intakes (DRI)—estimates of the amounts of nutrients required to prevent deficiencies and maintain optimal health and growth.

1.    EAR = Estimated Average Requirement

2.    RDA = Recommended Dietary Allowance RDA = EAR + 2SD_EAR

3.    AI = Adequate Intake

4.    UL = Tolerable Upper Intake Level

·         Saturated fatty acids with carbon chain lengths of 14 (myristic) and 16 (palmitic) are most potent in increasing the serum cholesterol. Stearic acid (18 carbons—found in many foods including chocolate) produces only modest increases in blood cholesterol.

Monounsaturated fats lower both total plasma cholesterol and LDL cholesterol, but maintain or increase HDL cholesterol. This ability of monounsaturated fats to favorably modify lipoprotein levels may explain, in part, the observation that Mediterranean cultures, with diets rich in olive oil (high in monounsaturated oleic acid), show a low incidence of CHD.

Polyunsaturated fats: The effects of polyunsaturated fatty acids (PUFAs) on cardiovascular disease is influenced by the location of the double bonds within the molecule.

1.    n-6 Fatty acids: (ω-6 fatty acids) Consumption of fats containing n-6 polyunsaturated fatty acids, principally linoleic acid (18:2, Δ9,12) obtained from vegetable oils, lowers plasma cholesterol when substituted for saturated fats. Plasma LDL are lowered, but HDL, which protect against CHD, are also lowered. Nuts, avocados, olives, soybeans, and various oils, including sesame, cottonseed, and corn oil, are common sources of these fatty acids

2.    n-3 Fatty acids: Dietary n-3 polyunsaturated fats suppress cardiac arrhythmias, reduce serum triacylglycerols, decrease the tendency for thrombosis, lower blood pressure, and substantially reduce risk of cardiovascular mortality, but they have little effect on LDL or HDL cholesterol levels. The n-3 polyunsaturated fats are found in plants (mainly α-linolenic acid—an essential fatty acid), and in fish oil containing docosahexaenoic acid and eicosapentaenoic acid. The acceptable range for α-linolenic acid is 0.6 to 1.2 percent of total calories.

Trans fatty acids are chemically classified as unsaturated fatty acids, but behave more like saturated fatty acids in the body, that is, they elevate serum LDL (but not HDL), and they increase the risk of CHD. Trans fatty acids do not occur naturally in plants, but occur in small amounts in animals.

·         Glycemic index is defined as the area under the blood glucose curves seen after ingestion of a meal with carbohydrate-rich food, compared with the area under the blood glucose curve observed after a meal consisting of the same amount of carbohydrate in the form of glucose or white bread.

·         Formerly obese patients have a particularly difficult time maintaining their reduced body weight. The observation that fat cells are never lost emphasizes the importance of preventing obesity in the first place.

·         In the liver, fatty acids are converted to triacylglycerols, which are packaged and secreted in VLDL. Chylomicrons are synthesized from dietary lipids by the intestinal mucosal cells following a meal. Because lipoprotein degradation catalyzed by lipoprotein lipase in adipose tissue  is low in diabetics, the plasma chylomicron and VLDL levels are elevated, resulting in hypertriacylglycerolemia.

·         In the fed state, most of the enzymes regulated by these covalent modifications are in the dephosphorylated form and are active. Three exceptions are glycogen phosphorylase kinase , glycogen phosphorylase, and hormone-sensitive lipase of adipose tissue, which are inactive in their dephosphorylated state.

·         Alcoholic = Wernicke’s encephalopathy (temporal lobe) - ataxia, nystagmus

o   Korsakoff (Mammilary bodies) - confabulation, psychosis

·         Sun can breakdown riboflavin → reason why milk is no longer stored in glass bottles.

FAD and FMN are derived from riboFlavin (B2 = 2 ATP).

• NAD derived from Niacin (B3 = 3 ATP).

·         Vitamin B4 = Lipoic acid

·         Vitamin B5 = Pantothenic acid → CoA

·         Vitamin B6 = Pyridoxine Cofactor for all TRANSAMINASES (AST/ALT)

·         Biotin is Cofactor for all CARBOXYLASES

·         Mg²⁺  is Co-factor for ALL KINASES and PTH

·         Trace Elements:

1. Chromium - neede in Insulin action
2. Selenium - necessary for heart
3. Manganese - xanthine oxidase

·         AST:ALT RATIO

Viruses (Hepatitis) will breakdown only the cell Wall and let AST & alt to spill out

o    AST/ALT < 2:1

Alcohol will dissolve both the cell membrane and the mitochonridal membrane and let ↑AST  ALT out

o    AST/ALT > 2:1

Ethanol increases NADH/NAD+ ratio in liver, causing diversion of pyruvate hypoglycemia to lactate and OAA to malate, thereby inhibiting gluconeogenesis and leading to hypoglycemia. This altered NADH/NAD+ ratio is responsible for the hepatic fatty change (hepatocellular steatosis) seen in chronic alcoholics (shunting away from glycolysis and toward fatty acid synthesis).

·         NAD+ is generally used in catabolic processes to carry reducing equivalents away as NADH. NADPH is used in anabolic processes (steroid and fatty acid synthesis) as a supply of reducing.

·         Arsenic inhibits lipoic acid. (vomiting, rice water stool, garlic breath)

·         The word beriberi is Singhalese for “I cannot,” referring to muscular atrophy and paralysis caused by the inflammation of multiple nerves (polyneuritis).

·         In order for pyruvate carboxylase to be ready to function, it requires biotin, Mg2+, and Mn2+. It is allosterically activated by acetyl-CoA.

·         Pantothenic acid combines with the amino acid cysteine to become the pentetheine sulfhydryl component of coenzyme A (CoA) and acyl carrier protein (important for fatty acid synthesis). Acetyl-CoA is the activated form of acetate employed in acetylation reactions, including the citric acid cycle and lipid metabolism. Loss of myelin in Hallavorden-Spatz disease correlates with a role for activated pantothenic acid as a cofactor for fatty acid synthesis and as a carrier of acyl chains (which must be added to glycerol to form triacylglycerols, alkylacylglycerols (ether lipids), and (by acyl addition to sphingosine) cerebrosides, sphingomyelin, and gangliosides.

Mutations with severe impact on panthothenic acid kinase (mediating activation by its phosphorylation) present with neurologic signs in infancy (e.g., infantile neuroaxonal dystrophy while those with less impact present in the second or third decades with cognitive decline, dementia, and psychiatric symptoms (e.g., Hallavorden-Spatz disease)

·         The vitamin K–dependent γ-carboxylation of prothrombin is a posttranslational modification that occurs as nascent prothrombin is synthesized on liver rough endoplasmic reticulum and passes into the lumen of the reticulum. The anticoagulants warfarin and dicumarol are structural analogues that block the γ-carboxylation of prothrombin by substituting for vitamin K. Hence, the prothrombin produced has a weak affinity for Ca2+ and cannot properly bind to platelet membranes in order to be converted to thrombin. Exposure of the fetus to warfarin during maternal therapy can produce a syndrome involving small, “fleur-de lys” nose and skeletal defects.

·         The vitamin biotin is the cofactor required by carboxylating enzymes such as acetyl-CoA, pyruvate, and propionyl-CoA carboxylases. The fixation of CO2 by these biotin-dependent enzymes occurs in two stages. In the first, bicarbonate ion reacts with (ATP) and the biotin carrier protein moiety of the enzyme; in the second, the “active CO2” reacts with the substrate—e.g., acetyl-CoA.

·         The almost universal carrier of acyl groups is coenzyme A (CoA). However, acyl carrier protein (ACP) also functions as a carrier of acyl groups. In fatty acid synthesis, ACP carries the acyl intermediates. The reactive prosthetic group of both ACP and CoA is a phosphopantetheine sulfhydryl. In ACP, the phosphopantetheine group is attached to the 77-residue polypeptide chain via a serine hydroxyl. In CoA, the phosphopantetheine is linked to the 5′-phosphate of adenosine that is phosphorylated in its 3′-hydroxyl.

·         Mutations in the multipeptide pyruvate dehydrogenase complex occur in Leigh disease, an end phenotype of many mutations that simulate the lactic acidosis and encephalopathy accompanying acute forms of thiamine deficiency (beri beri).

·         THF is required in two steps of purine synthesis and thus required in the de novo synthesis of ATP and GTP. Although de novo synthesis of the pyrimidine ring does not require tetrahydrofolate, the methylation of dUMP to form thymine from uracil does.

Methotrexate inhibits dihydrofolate reductase, depletes THF pools, and thus would elevate substrates of enzymes dependent on this cofactor like dUMP. THF is also a cofactor for methionine synthase that coverts homocysteine to methionine, an enzyme deficient in one form of homocystinuria.

·         The vitamin riboflavin (vitamin B2) is a precursor of two cofactors involved in electron transport systems, riboflavin 5′-phosphate, also known as flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). Strictly speaking, these compounds are not nucleotides, as they contain the sugar alcohol ribitol, not ribose.

·         The coenzyme pyridoxal phosphate is a versatile compound that aids in amino acid transaminations, deaminations, decarboxylations, and transulfurations. It is also important for operation of glycogen phosphorylase. A common feature of these reactions is formation of a Schiff-base intermediate with a specific lysine group at the active site of the appropriate enzymes.