Exam 3

FMN and FAD are coenzyme forms of [blank].

Riboflavin

Wernicke's Encephalopathy

most severe form of Wernicke-Korsakoff Syndrome (thiamin deficiency) seen with long-term chronic abuse of alcohol

acetylcholine

neurotransmitter important for memory, muscle control, mood, and other brain and nervous system functions

THF functions in the body as a coenzyme to accept [blank].

one carbon unit

Which amino acids are essential to biosynthesis of purine?

the amino acids glutamine, glycine, and aspartate are essential to biosynthesis

Which amino acids are essential to biosynthesis of creatine?

the amino acids glycine, argine, and SAM (obtained from meat) are essential to biosynthesis

Which amino acids are essential to biosynthesis of carnosine?

the amino acids histidine and beta alanine (can be obtained from meat) are essential to biosynthesis

Key functions of glutamate?

- Acts as an excitatory neurotransmitter in the brain and spinal cord. - Can be decarboxylated to form gama aminobutyrate (GABA) which acts as an inhibitory transmitter

Riboflavin deficiencies

- Ariboflavinosis: acute deficiency that rarely occurs in isolation but most often accompanies by other nutrient deficiencies - Chelosis: painful lesions on the outside of lips - Glossitis: inflammation of the tongue - Swollen oral cavity

Vitamin B12 (cobalamin) deficiency

- B12 deficiency -> accumulation of methylmalonyl CoA -> neurological damage - megoblastic macrocytic anemia

What can glutamine be converted to?

- Can be transaminated with pyruvate to form alanine (transported to liver) and alpha ketoglutarate (oxidized via the TCA cycle) - Can be converted to proline and enter portal blood - Can combine with aspartate to form ornithine which can create citrulline which can leave enterocytes to be taken up by the liver and kidney for urea cycle

Megoblastic Macrocytic Anemia (from Folate deficiency)

- Caused by a deficiency of folate/B12 due to decrease DNA synthesis and failure of the cells to divide properly - RBC's are larger than normal and fewer in normal - Symptoms: fatigue, weakness, headaches, irritability, difficulty

Biotin (B7)

- Coenzyme form: Coenzyme A - Function: functions as a coenzyme required for four carboxylases - AI: 30 ug/day - Deficiency: rare - In humans, deficiency is associated with high intake of raw eggs or a metabolic abnormality (avidin is a glycoprotein found in raw egg whites, which can bind to biotin tightly and prevent its absorption. Cooking eggs does not compromise biotin absorption because heat kills avidin) - Symptoms: lethargy, depression, hallucinations, muscle pain, alopecia, dermatitis

Pantothenic Acid

- Coenzyme form: Coenzyme A - Function: metabolism of CHO, lipids, and protein relies on varying degrees of CoA. Also forms acetyl CoA from pyruvate - AI: 6 mg/day for adults - Deficiency: quite unlikely as It is found in virtually all plant and animal foods, but can occur with multiple nutrient deficiencies Associated with burning feet syndrome (numbness of toes, burning sensation in the feet, vomiting, fatigue, weakness)

Thiamin (Vitamin B1)

- Coenzyme form: Thiamin Diphosphate (TDP) or Thiamin Pyrophosphate (TPP) - Function: Required for energy transformation/generation in TCA cycle (for pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, and branched chain alpha keto acid dehydrogenase); synthesis of NADPH and ribose (PPP pathway) - no adverse effects are associated with high intakes from food or supplements - Deficiency results in Beri Beri or Wernicke-Korsakoff Syndrome - RDA: 1.2mg/day for males; 1.1mg/day for females

Riboflavin (B2)

- Coenzyme form: flavin mononucleotide (FMN) and adenine dinucleotides (FAD) - Function: act as oxidizing agents due to their ability to accept a pair of hydrogens and electrons (FAD->FADH2; FMN->FMNH2). - RDA: 1.3mg/day for males, 1.1mg/day for females - toxicity has not been reported - deficiencies: ariboflavinosis, chelosis, glossitis, swollen oral cavity

Niacin (B3)

- Coenzyme forms: Nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP) - Function: approximately 200 dehydrogenase enzymes require NAD or NADPH as the coenzyme - RDA: we can synthesize niacin, so we use niacin equivalents (NE - 16mg/NE/day for males, 14mg/NE/day for females) - Deficiency: Pellagra

What types of reactions does vitamin c function as a reducing agent (electron donor) in?

- Collagen synthesis - Carnitine synthesis - Tyrosine catabolism (increases) - Norepinephrine & serotonin synthesis - Antioxidant synthesis

Megoblastic Macrocytic Anemia (from B12 deficiency)

- Indistinguishable from megoblastic macrocytic anemia from folate deficiency - High folate intake and folate therapy can "mask" the B12 deficiency, but neurological manifestations will persist (Numbness in extremities, Abnormal gait, Ataxia, Loss of sense of relative position, Diminished memory, psychosis and delirium)

Vitamin B6 RDA

- Males/Females 19-50 yrs = 1.3 mg/day - Males 51+ yrs: = 1.7 mg/day - Females 51+ yrs: = 1.5 mg/day UL = 100 mg/day for adults

Vitamin B12 (cobalamin) coenzyme forms

- Methylcobalamin: required for the regeneration of methionine from homocystein -Deoxyadenosylcobalamin: required for the conversion of methylmalonyl CoA to succinyl CoA

Glutathione

- Nitrogen containing non-protein compound - functions as an antioxidant agent that scavenges up free radicals and protects against oxidative damage - the amino acids glutamate, cystein, and glyceine are essential to biosynthesis

Pyrimidine

- Nitrogen containing non-protein compound - functions as an important structural component of DNA and RNA (building block of DNA) - the amino acids glutamine and aspartate are essential to biosynthesis

Purine

- Nitrogen containing non-protein compound - functions as an important structural component of DNA and RNA (building blocks of DNA) - the amino acids glutamine, glycine, and aspartate are essential to biosynthesis

Carnosine

- Nitrogen containing non-protein compound - has a possible role in anti-aging - the amino acids histidine and beta alanine (can be obtained from meat) are essential to biosynthesis

Choline

- Nitrogen containing non-protein compound - needed to produce acetylcholine; also plays important roles in modulating gene expression, cell membrane signaling, lipid transport and metabolism, and early brain development - Phosphatidycholine is needed for biosynthesis

Carnitine

- Nitrogen containing non-protein compound - required for transport of long chain fatty acids across mitochondrial membranes - the amino acid lysine (obtained from meat) is essential to biosynthesis

Creatine

- Nitrogen containing non-protein compound - the first line of energy used before muscle glycogen is broken down to produce ATP - the amino acids glycine, argine, and SAM (obtained from meat) are essential to biosynthesis

Vitamin B6 Coenzyme functions

- PLP is associated with >140 enzymes as a coenzyme, the majority of which are involved in amino acid metabolism - Transamination reactions (AST & ALT are most common) - Synthesis of neurotransmitters is dependent on PLP.

Riboflavin functions as an oxidizing agent in which reactions?

- Succinate dehydrogenase (TCA cycle) - Fatty acyl CoA dehydrogenase (fatty acid beta-oxidation) - A step in niacin synthesis from tryptophan - Synthesis of some neurotransmitters from AA's

Folate - Coenzyme forms and functions

- THF and THF derivatives: Tetrahydrofolate (THF) functions to accept different one carbon units, forming different THF derivatives, which donate the one carbon units in various synthetic reactions (amino acid synthesis, purine synthesis, pyrimidine synthesis) - functions to regenerate methionine from homocysteine - important function in Purine and pyrimidine synthesis (DNA synthesis and cell division)

Vitamin C (ascorbic acid)

- a 6-carbon compound derived from glucose - Functions as a reducing agent (electron donor) in several reactions - found in citrus fruits, tomatoes, peppers, etc as ascorbic acid - Deficiency results in scurvy - can enhance the absorption of nonheme iron either by reducing iron from Fe3+ state to Fe2+ state or by forming a soluble complex with the Fe2+

Serotonin

- excitatory neurotransmitter in the CNS, and in circulation can act as a vasoconstrictor and stimulator of smooth muscle contraction, also affects sleep, mood, appetite, memory and learning - tryptophan is needed for biosynthesis

Vitamin B12 (cobalamin)

- found in animal products including fish, meat, poultry, eggs, milk, and milk products, fortified breakfast cereals - readily absorbed in the last part of the small intestine (ileum) when combined with intrinsic factor, a protein found in the stomach - deficiency can lead to an accumulation of methylmalonyl CoA which can lead to neurological damage, or megoblastic macrocytic anemia

Phosphatidycholine

- found in plasma membrane - can be obtained from the diet as lecithin from eggs, organ meats, and some seafood - needed for the biosynthesis of choline

Vitamin B6 Megadose is advocated for the prevention and treatment of what? What is long term megadose usage associated with?

- hyperhomocysteinemia, morning sickness, premenstrual syndrome, depression, and muscular fatigue - Long term megadose associated with numbness in the feet and hands, severe ataxia, impaired tendon reflexes

Folate deficiency diseases

- megoblastic macrocytic anemia - neural tube defects

Histamine

- neurotransmitter needed for alertness and attention - histidine is essential for the biosynthesis

Catecholamines

- neurotransmitter needed for motor control, cognition and emotion - tyrosine is essential for the biosynthesis

Beri Beri

- results from thiamin (b1) deficiency - Very prevalent in areas where polished grains comprise 80% of the diet i. Dry Beriberi: muscle wasting and neurological problems. Usually do not include cardiac problems. ii. Wet Beriberi: greater number of cardiac problems encountered, such as enlarged heart, rapid heartbeat, etc. Edema starts at feet and progresses upward iii. Infantile Beriberi: has a very rapid onset. Anorexia, vomiting, lactic acidosis, altered heart rate, and enlarged heart.

Glutamine Functions

- source of energy (glutamine -> glutamate-> alpha ketoglutarate->TCA) - Increases/stimulates mucosal cell proliferation (trophic effect) - Prevents atrophy of gut mucosa and prevents bacterial translocation in the gut (leaky gut) by increasing biosynthesis of mucin (protein component of mucous)

Functions of the alanine glucose cycle

- transports nitrogen from the muscle to the liver where it can be excreted as urea - Regenerate glucose

Which populations are at risk of B12 deficiency?

1. Elderly: caused by decrease gastric acid secretion 2. Vegans 3. those with pernicious anemia: autoimmune diseases, gastric parietal cells are damaged, HCI production and IF synthesis are impaired 4. Inflammatory bowel disease 5. Gastric bypass surgery 6. Gastric atrophy

Explain the Alanine-Glucose Cycle

1. G6P goes through glycolytic pathway, and gets converted to pyruvate 2. Pyruvate is transaminated with glutamate to form alanine and alpha ketoglutarate 3. Alanine leaves muscle and travels to the liver where it is transaminated back to pyruvate. Alpha ketoglutarate is transaminated to glutamate 4. Glutamate is deaminated to remove nitrogen group, and enters urea cycle 5. Pyruvate goes back through gluconeogenic pathway to be converted to glucose

Neural tube defects

1. In the embryotic stage of development around the 19th day after fertilization, the neural tube begins to form 2. If the bottom of the neural tube fails to close, then SPINA BIFIDA develops 3. In severe cases the spinal cord protrudes through the lower back 4. Affects 1/1000 pregnancies in the US

Recommended intake for Folate (DFEs)

1. Men and Women: 400 ug DFE/d 2. Pregnancy: 600 ug DFE/d 3. Lactation: 500 ug DFE/d

What percentage of dietary essential amino acids are used up by the enterocytes?

30-40%

[Blank] is required for the regeneration of methionine from homocysteine as the donor of the methyl group.

5-methyl THF

1 mg nicotinamide or nicotinic acid = ? mg tryptophan

60 mg tryptophan

How much dietary glutamate is used by the enterocytes?

90% (10g/day) of glutamate that is absorbed from the diet is used/metabolized by the enterocytes

Vitamin B6 deficiency can result in [blank].

A high blood homocysteine level

What is the Methyl folate trap

B12 deficiency can lead to lowered levels of methionine synthetase, which results in a functional folate deficiency by trapping an increased proportion of folate as the 5-methyl derivative

Vitamin B6

Coenzyme Forms: exists in 6 interchangeable forms - Pyridoxine (PN), Pyridoxal (PL), Pyridoxamine (PM), Pyridoxine Phosphate (PNP), Pyridoxal Phosphate (PLP), Pyridoxamine Phosphate (PMP) Functions: - PLP is associated with >140 enzymes as a coenzyme, the majority of which are involved in amino acid metabolism - Transamination reactions (AST & ALT are most common) - Synthesis of neurotransmitters is dependent on PLP. RDA - Males/Females 19-50 yrs = 1.3 mg/day - Males 51+ yrs: = 1.7 mg/day - Females 51+ yrs: = 1.5 mg/day UL = 100 mg/day for adults Deficiency: rare bc found in most foods

Pantothenic Acid deficiency

Deficiency: quite unlikely as It is found in virtually all plant and animal foods, but can occur with multiple nutrient deficiencies. Associated with burning feet syndrome: numbness of toes, burning sensation in the feet, vomiting, fatigue, weakness

Biotin deficiency

Deficiency: rare - In humans, deficiency is associated with high intake of raw eggs or a metabolic abnormality (avidin is a glycoprotein found in raw egg whites, which can bind to biotin tightly and prevent its absorption. Cooking eggs does not compromise biotin absorption because heat kills avidin) - Symptoms: lethargy, depression, hallucinations, muscle pain, alopecia, dermatitis

All the B vitamins [blank].

Form a part of one or more coenzymes

Can humans synthesize vitamin C? Why or why not?

Humans are one of the few mammals unable to synthesize vitamin C because we lack the enzyme gulonolactone oxidase

Which of the following is required as a coenzyme for the regeneration of methionine from homocysteine?

methylcobalamin

Folate deficiency and vitamin B12 deficiency can both result in [blank].

Megloblastic, macrocytic anemia

One ug (microgram) DFE = ? ug food folate, ? ug folic acid from a supplements or fortified food consumed with a meal, and ? ug of folic acid from a supplement taken on an empty stomach

One ug DFE = 1 ug of food folate, 0.6 ug of folic acid from a supplement or fortified food consumed with a meal, 0.5 ug of folic acid from a supplement taken on an empty stomach

Which of the following vitamin is a part of coenzyme A?

Pantothenic Acid

[Blank] was once prevalent in the southern U.S. where corn was a main dietary staple in the early 1900s.

Pellagra

Which amino acid is essential to biosynthesis of choline?

Phosphatidycholine

The key coenzyme form of vitamin B6 is [blank].

Pyridoxal phosphate (PLP)

How is RDA for Folate expressed?

RDA is expressed as DFE, which accounts for the high bioavailability of folic acid taken as supplements versus the lower bioavailability of folate in foods

Vitamin C deficiency results in which disease?

Scurvy -impaired collagen synthesis leads to most of the clinical signs and symptoms of scurvy - symptoms include: Bleeding gums, small skin discolorations due to ruptured blood vessels, sublingual hemorrhages, easy bruising, impaired wound and fracture healing, joint pain, loose and decaying teeth

Explain Purine and pyrimidine synthesis (DNA synthesis and cell division) as a function of THF

THF is involved in purine and pyrimidine synthesis, making folate essential for DNA synthesis and cell division - 5-10 methylene THF is required for thymidine synthesis - 10-formyl THF is required for adenine and guanine formation - Cells with a short life (enterocytes, and RBCs) are dependent on adequate folate levels

Characteristics of Megloblastic, macrocytic anemia

The cell division of red blood cells is impaired & The number of red blood cells is decreased.

Wernicke-Korsakoff Syndrome

Thiamin deficiency associated with alcoholism; Decreased thiamin intake due to decreased food intake; decreased absorption; an increased requirement because of liver damage - Ophthalmoplegia: paralysis of the ocular muscles - Nystagmus: constant, involuntary eyeball movement - Ataxia: impaired muscle coordination - Loss of recent memory, confusion - Without treatment, brain damage can occur

Vitamin B6 UL

UL: 100 mg/day for adults

What happens to unused glutamine?

Unused glutamine can be catabolized to glutamate and NH3+ which is taken to the liver for urea cycle

Large doses of niacin can be used to treat [blank].

hypercholesterolemia

Explain the regeneration of methionine from homocysteine as a function of THF

When SAM concentration is low, homocysteine can be remethylated to methionine (in amino acid metabolism). This requires folate as 5-methyl THF as a methyl donor - Vitamin B12 in the form methylcobalamin is attached to methionine synthase - Cobalamin picks up the methyl group from 5 methyl THF to generate methylcobalamin and THF - Methylcobalamin serves as the methyl donor for converting homocysteine to methionine

All B vitamins form ________

a part of one or more coenzymes; coenzymes for thiamin, riboflavin, niacin, pantothenic acid, biotin, and B6 are needed particularly for energy/macronutrient metabolism

Vitamin B6 is critical for the metabolism of [blank] in the body.

amino acids

Vitamin C is required for the synthesis of [blank].

carnitine, tyrosine, norepinephrine

Food sources of Vitamin C (acorbic acid) include

citrus fruits, tomatoes, potatoes, peppers, kiwi, broccoli, strawberries, brussels sprouts, cantaloupe

[Blank] is required as a coenzyme for pyruvate carboxylase and acetyl CoA carboxylase.

coenzyme A

The coenzyme form of thiamin is involved in [blank].

energy transformation

The human body can synthesize vitamin C.

false

What is the most common deficiency in the US?

folate

GI manifestations associated with pellagra

glossitis, cheilosis, nausea, vomiting, and diarrhea

Neurological manifestations associated with pellagra

headaches, apathy, loss of memory, depression, fearful and confused, hallucinations, etc.

Which amino acid is needed for the biosynthesis of histamine?

histidine

Vitamin C is needed for collagen synthesis because it is required for the [blank] reaction of proline and lysine residues.

hydroxylation

Vitamin C can improve the absorption of [blank] by the small intestine.

iron

Megadoses of Niacin (B3) are used to treat what? What symptoms can megadoses cause?

large doses (approx. 3g/day) used to treat hypercholesterolemia, and can significantly lower total serum cholesterol and LDL while increasing HDL. Can cause: - niacin blush/vasodilatory reactions such as flushing and redness along with burning, itching, tingling, and headaches - Heartburn, nausea, and vomiting - Possible injury to the liver - High blood glucose

400mg of Riboflavin are effective in treating what?

migraine headaches

Vitamin B6 deficiency

rare as B6 is found in virtually all foods - 1950s deficiency occurred in infants due to extreme heat treatment of infant formula; they developed hyperirritability and had recurrent convulsive seizures - Clinical manifestations of deficiency: ataxia, weakness, hyperirritability, depression and confusion followed by convulsions, dermatitis, angular cheilosis, glossitis, microcytic anemia (impaired heme synthesis), high blood homocysteine (risk factor for heart disease)

Which amino acids are essential to biosynthesis of pyrimidine?

the amino acids glutamine and aspartate are essential to biosynthesis

By donating electrons, vitamin C (ascorbic acid) functions as a [blank] agent in the body.

reducing

Pellagra

results from Niacin deficiency - Corn lacks niacin, and was main dietary staple in early 1900s - Joseph Goldberger determined that a pellagra preventative factor was missing from corn I 1914 - In 1937, niacin was isolated and shown to cure pellagra - Four D's: dermatitis, dementia, diarrhea, and death

Dermatitis

similar to sunburn at first and on areas exposed to sun

Which amino acids are essential to biosynthesis of carnitine?

the amino acid lysine (obtained from meat) is essential to biosynthesis

Which amino acids are essential to biosynthesis of glutathione?

the amino acids glutamate, cystein, and glyceine are essential to biosynthesis

Which amino acid is needed for the biosynthesis of serotonin?

tryptophan

Which amino acid is needed for the biosynthesis of catecholamines?

tyrosine