·
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 + 2SDEAR
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:
- Chromium - neede in Insulin action
- Selenium - necessary for heart
- 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.
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